HEKOTOS CHESTY COUGH SYRUP

Indications

• Constipation
• Bowel cleansing

Dosage

Children: Child 1–11 months: 1 g as required, Child 1–11 years: 2 g as required, Child 12–17 years: 4 g as required.

Adults: 4 g as required, usually administered rectally.

Mechanism of action

When administered rectally, glycerol exerts a hygroscopic and/or local irritant action, drawing water from the tissues into the feces and reflexively stimulating evacuation. It decreases intraocular pressure by creating an osmotic gradient between the blood and intraocular fluid, causing fluid to move from the aqueous and vitreous humors into the bloodstream. Glycerol is classified as a hyperosmotic laxative and may also have lubricating and fecal softening effects.

Pharmacodynamics

Glycerol is commonly classified as an osmotic laxative, acting through its local irritant effects and possibly having lubricating and fecal softening actions. Glycerol suppositories usually produce effects within 15 to 30 minutes, providing quick relief from constipation.

Pharmacokinetics

Glycerol is rapidly absorbed through the gastrointestinal tract. It is metabolized in the liver and other tissues, with a half-life that varies depending on the route of administration. Following rectal administration, glycerol is primarily excreted in urine. The pharmacokinetics may vary based on dosage forms and individual patient factors.

Contra-indications

• Acute abdominal conditions
• Acute inflammatory bowel disease
• Intestinal obstruction
• Severe dehydration

Adverse effects

• Abdominal cramps
• Asthenia
• Gastrointestinal disorders
• Hypermagnesaemia
• Skin reactions
• Urine discolouration

Precautions

• Avoid prolonged contact with skin, especially in incontinent patients or infants wearing nappies due to the risk of irritation and excoriation.
• Excessive use may cause diarrhea and related effects such as hypokalaemia.

Pregnancy

Manufacturers advise avoidance due to limited information available.

Breast-feeding

Manufacturers advise avoidance as there is no information available.

Storage

Store at room temperature, away from direct sunlight.

Formulations

• Glycerol 1g suppositories
• Glycerol 2g suppositories
• Glycerol 4g suppositories
• Glycerol oral suspension

Dosage

Children: Refer to the specific product guidelines for appropriate use, as dosages may vary depending on the product formulation.

Adults: Refer to the specific product guidelines for appropriate use, as dosages may vary depending on the product formulation.

Mechanism of action

Aspartame is metabolized into aspartic acid, phenylalanine, and methanol. These components are then absorbed into the bloodstream and utilized in normal physiological processes, similar to how these amino acids are used when derived from protein-rich foods.

Pharmacodynamics

Aspartame functions as a low-calorie sweetener, providing sweetness without significant caloric contribution. It is composed of naturally occurring amino acids, aspartic acid and phenylalanine, which are utilized by the body in the same way as those derived from dietary proteins. The sweetening effect of aspartame is primarily due to its high sweetness potency compared to sucrose.

Pharmacokinetics

Upon ingestion, aspartame is hydrolyzed in the gastrointestinal tract into its individual components: aspartic acid, phenylalanine, and methanol. These metabolites are then absorbed into the bloodstream. They do not accumulate in the body and are utilized in metabolic processes similar to those of their natural counterparts found in food.

Contra-indications

• Phenylketonuria (PKU)

Adverse effects

• Headaches
• Allergic reactions
• Gastrointestinal disturbances
• Mood changes

Precautions

• Use with caution in individuals with phenylketonuria due to phenylalanine content.

Pregnancy

Considered safe for use during pregnancy, but it is advisable to consult with a healthcare provider.

Breast-feeding

Considered safe for use during breastfeeding, but it is advisable to consult with a healthcare provider.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Tablets
• Powder
• Liquid sweeteners

Indications

• Food preservative
• Treatment of urea cycle disorders
• Metabolic disorders involving benzoyl-CoA

Dosage

Children: Refer to the BNF for Children for specific dosing guidelines based on condition.

Adults: Refer to the BNF for specific dosing guidelines based on condition.

Mechanism of action

Benzoate acts mainly by inhibiting the growth of bacteria and fungi through its ability to lower the pH, creating an environment that is less favorable for microbial growth. It is also involved in metabolic pathways where it helps in the conjugation of toxic substances, facilitating their excretion from the body.

Pharmacodynamics

Benzoate is known for its antimicrobial properties, which are particularly effective against a wide range of fungi and bacteria. Its efficacy as a preservative is due to its ability to penetrate microbial cell membranes and disrupt their metabolic processes. Additionally, it has been observed to modulate various metabolic pathways, particularly those associated with aromatic compound degradation.

Pharmacokinetics

After ingestion, benzoate is rapidly absorbed in the gastrointestinal tract. It is metabolized primarily in the liver, where it undergoes conjugation with glycine to form hippurate, which is then excreted in the urine. The half-life of benzoate varies depending on individual metabolic rates but is generally short due to its efficient conversion and excretion.

Pregnancy

There is limited data on the use of benzoate in pregnancy. Consultation with healthcare professionals is advised before use.

Breast-feeding

Limited data is available on the excretion of benzoate in breast milk. Caution is recommended when administering to nursing mothers.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Indications

• Support for immune health
• Management of inflammation
• Antioxidant support
• Vascular health improvement

Dosage

Children: Refer to established guidelines for dosing, as specific dosing may vary based on the form of blackcurrant used (fresh fruit, juice, extract).

Adults: Refer to established guidelines for dosing, as specific dosing may vary based on the form of blackcurrant used (fresh fruit, juice, extract).

Mechanism of action

The active compounds in blackcurrant, particularly anthocyanins, exert their effects through various mechanisms including antioxidant activity, which helps neutralize free radicals and reduce oxidative stress. They may also modulate inflammatory pathways and enhance immune response, contributing to the overall health benefits associated with blackcurrant consumption.

Pharmacodynamics

Blackcurrant demonstrates anti-inflammatory and antioxidant properties, which may improve cellular health and reduce the risk of chronic diseases. The anthocyanins in blackcurrant have been shown to support vascular health by improving endothelial function and reducing blood pressure. Additionally, its compounds may enhance the production of cytokines, which play a crucial role in immune response.

Pharmacokinetics

Blackcurrant compounds are absorbed in the gastrointestinal tract, with peak plasma concentrations occurring within a few hours post-consumption. The bioavailability of anthocyanins can vary based on several factors including the form of blackcurrant consumed (fresh, juice, extract). The metabolites are primarily excreted via urine. The pharmacokinetics can be influenced by the presence of other dietary components.

Pregnancy

There is insufficient reliable information on the use of blackcurrant during pregnancy. It is recommended to consult a healthcare provider before use.

Breast-feeding

Limited information is available regarding the safety of blackcurrant during breastfeeding. Consultation with a healthcare provider is advisable.

Storage

Store in a cool, dry place away from direct sunlight. Ensure that it is kept out of reach of children.

Indications

• Chronic bronchitis
• Asthma
• Bronchiectasis
• Pneumonia
• Respiratory tract infections with productive cough

Dosage

Children: Refer to the BNF for Children for specific paediatric dosing recommendations.

Adults: Refer to the BNF for specific dosing information.

Mechanism of action

Bromhexine aids in mucus clearance by reducing the viscosity of mucus and activating the ciliary epithelium, allowing secretions to be expelled from the respiratory tract. Additionally, bromhexine has been shown to inhibit the transmembrane serine protease 2 receptor (TMPRSS2), which plays a crucial role in viral respiratory diseases. This inhibition may help in preventing or treating various respiratory illnesses, including COVID-19, by blocking viral entry into cells.

Pharmacodynamics

Bromhexine thins airway secretions, thus improving breathing and alleviating discomfort associated with thick mucus in the airways. Its action is particularly beneficial in respiratory disorders where mucus obstruction is a significant issue.

Pharmacokinetics

Bromhexine is well absorbed after oral administration, with peak plasma concentrations typically reached within 1 to 2 hours. It is metabolized in the liver, primarily to ambroxol, which is its active metabolite. The elimination half-life of bromhexine is approximately 8 to 12 hours, and it is excreted mainly through urine. The pharmacokinetics can be influenced by factors such as liver function and concurrent medications.

Adverse effects

• Gastrointestinal disturbances
• Nausea
• Vomiting
• Diarrhea
• Allergic reactions

Precautions

• Use with caution in patients with peptic ulcer disease
• Monitor patients with asthma or bronchospastic conditions

Pregnancy

Bromhexine should be used during pregnancy only if clearly needed and after careful consideration of the potential benefits and risks.

Breast-feeding

Bromhexine is excreted in breast milk; caution should be exercised when administering to nursing mothers.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Tablets
• Syrup
• Solution for inhalation

Indications

• Dry eye syndrome
• Ocular lubrication
• Thickening agent in pharmaceutical formulations
• Food industry as a stabilizer and emulsifier

Dosage

Children: For paediatric use, refer to specific product guidelines and consult a healthcare professional for appropriate advice.

Adults: For dry eye treatment, apply as needed, typically 1 drop in each affected eye. Refer to specific product guidelines for exact formulation and frequency.

Mechanism of action

Carboxymethylcellulose works by forming a gel-like structure when it interacts with water, which helps retain moisture and provide lubrication. In ophthalmic applications, it acts as a protective agent for the ocular surface, reducing friction and providing comfort to patients with dry eye conditions.

Pharmacodynamics

The pharmacodynamic properties of carboxymethylcellulose are primarily related to its ability to increase viscosity and improve the stability of formulations. It does not undergo significant systemic absorption and exerts its effects locally, particularly in the gastrointestinal tract and on the ocular surface as a lubricant.

Pharmacokinetics

Carboxymethylcellulose is not absorbed significantly through the gastrointestinal tract when ingested, and its systemic bioavailability is negligible. When used in ophthalmic formulations, it acts locally on the eye without significant systemic effects. The elimination pathway is primarily through natural degradation and excretion of unabsorbed material.

Adverse effects

• Allergic reactions
• Skin irritation
• Gastrointestinal discomfort

Precautions

• Use with caution in patients with known hypersensitivity to cellulose derivatives
• Monitor for allergic reactions

Pregnancy

Carboxymethylcellulose is generally considered safe during pregnancy as it is not absorbed systemically.

Breast-feeding

Carboxymethylcellulose is considered safe during breastfeeding as it is not absorbed systemically.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Eye drops
• Oral suspensions
• Topical gels

Indications

• Acidulant in food and beverages
• Preservative in pharmaceutical formulations
• pH adjuster in various chemical preparations

Dosage

Children: Refer to product-specific guidelines for appropriate dosing based on formulation and indication.

Adults: Refer to product-specific guidelines for appropriate dosing based on formulation and indication.

Mechanism of action

Citric acid acts by chelating metal ions, which can enhance the solubility of certain compounds and improve their bioavailability. It also contributes to the acidity of the environment, which can influence enzymatic activity and metabolic pathways, particularly in the degradation of citronellol.

Pharmacodynamics

Citric acid exhibits mild pharmacological effects primarily attributed to its role in metabolic processes. It aids in the regulation of pH levels, which can impact enzymatic reactions and biochemical pathways. The acid's chelating properties may help to reduce the toxicity of certain metal ions in biological systems.

Pharmacokinetics

Citric acid is rapidly absorbed after oral administration and is metabolized in the liver. It undergoes conversion to various metabolites in the citric acid cycle, contributing to energy production. The elimination primarily occurs through urine, with minimal accumulation in the body.

Pregnancy

Citric acid is generally regarded as safe during pregnancy when used in food amounts. However, consult a healthcare provider for advice on medicinal use.

Breast-feeding

Citric acid is considered safe during breastfeeding when consumed in food amounts. For medicinal use, consult a healthcare provider.

Storage

Store in a cool, dry place away from direct sunlight.

Mechanism of action

The precise mechanism of action is not well-documented in the provided resources. However, compounds with similar molecular structures often interact with biological pathways through modulation of neurotransmitter systems or receptor activity.

Pharmacodynamics

Pharmacodynamics for compounds like Colour typically involve interactions at the cellular level, influencing physiological responses through receptor binding and modulation of signaling pathways. The specific effects and potency would depend on the context of use and formulation.

Pharmacokinetics

Information on the pharmacokinetics of Colour, including absorption, distribution, metabolism, and excretion, is not provided in the available resources. Generally, pharmacokinetic properties will vary significantly based on formulation and route of administration.

Pregnancy

Safety in pregnancy has not been established. Use only if the benefits outweigh the risks.

Breast-feeding

Caution is advised. There are no adequate studies in breastfeeding women.

Storage

Store in a cool, dry place, away from light. Keep out of reach of children.

Indications

• Aromatherapy
• Anxiety relief
• Mood enhancement
• Antimicrobial applications
• Pain management
• Anti-inflammatory treatments

Dosage

Children: Dosage for paediatric use of essences should be approached with caution and tailored to the child's age, weight, and condition. Refer to specific pediatric guidelines or consult a healthcare provider for appropriate dosing information.

Adults: Dosage for essences varies widely based on the specific type of essence and the intended use. It is essential to refer to specific guidelines or consult a healthcare provider for appropriate dosing information.

Mechanism of action

The mechanism of action of essences can vary depending on the specific substance in question. Generally, essential oils and herbal extracts act through a combination of phytochemical interactions, influencing neurotransmitter systems, modulating inflammation, and exhibiting antimicrobial properties. These compounds may interact with various receptors in the body, including G-protein coupled receptors and ion channels, leading to physiological responses.

Pharmacodynamics

Pharmacodynamics of essences is largely dependent on their chemical composition. Many essential oils contain terpenes, phenols, and other bioactive compounds that exhibit a range of effects such as antibacterial, antifungal, anti-inflammatory, and analgesic properties. The effects can vary based on concentration, route of administration, and individual patient factors, influencing their efficacy and safety.

Pharmacokinetics

The pharmacokinetics of essences involves absorption, distribution, metabolism, and excretion. Essential oils are typically absorbed through the skin or via inhalation and can be distributed throughout the body via the bloodstream. They are often metabolized by the liver, with various pathways leading to the formation of active or inactive metabolites. Excretion mostly occurs through urine, but some components may also be eliminated through bile or exhalation.

Pregnancy

The safety of essence during pregnancy has not been established. Consultation with a healthcare provider is recommended before use.

Breast-feeding

It is unclear whether essence is excreted in breast milk. Caution is advised, and it is best to consult a healthcare provider.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Dosage

Children: Refer to the BNF for Children for appropriate dosing information in paediatric cases, especially in instances of overdose.

Adults: Refer to the BNF for specific dosing information based on clinical circumstances, particularly in cases of overdose.

Mechanism of action

Ethylene glycol is metabolized by alcohol dehydrogenase to glycoaldehyde, which is subsequently converted to glycolic, glyoxylic, and oxalic acids. These metabolites contribute to anion gap metabolic acidosis and are responsible for tissue injury through the formation of insoluble calcium oxalate crystals.

Pharmacodynamics

The toxicity of ethylene glycol arises from its metabolites, particularly glycolic and oxalic acids. These compounds induce metabolic acidosis, lead to renal failure through calcium oxalate crystal deposition in the kidneys, and can cause neurological impairment. The anion gap increases due to the accumulation of these acids, leading to complications such as cardiovascular instability and potential multi-organ failure.

Pharmacokinetics

Ethylene glycol is rapidly absorbed after oral ingestion. It undergoes first-pass metabolism primarily in the liver, where it is converted into its toxic metabolites. The elimination half-life of ethylene glycol varies but is generally prolonged in cases of renal impairment. Renal excretion of metabolites contributes to the duration of toxicity, necessitating prompt medical intervention in cases of overdose.

Adverse effects

• Metabolic acidosis
• Renal failure
• CNS depression
• Hypocalcemia
• Cardiovascular collapse
• Pulmonary edema

Precautions

• Use with caution in patients with renal impairment
• Monitor for signs of metabolic acidosis
• Evaluate electrolyte levels, particularly calcium

Pregnancy

There is limited data on the safety of ethylene glycol in pregnancy. It should only be used if clearly needed.

Breast-feeding

It is unknown if ethylene glycol is excreted in human milk. Caution is advised.

Storage

Store in a tightly closed container at room temperature, away from heat and moisture.

Formulations

• Liquid

Indications

• Cough associated with respiratory tract infections
• Cough due to bronchial asthma
• Acute bronchitis
• Chronic obstructive pulmonary disease (COPD)
• Sinusitis

Dosage

Children: For children aged 6 to 12 years, the typical dosage is 100-200 mg every 4 hours as needed, not exceeding 1.2 g in 24 hours. For children aged 2 to 6 years, the dosage is generally 50-100 mg every 4 hours as needed, not exceeding 600 mg in 24 hours. Refer to the BNF for Children for specific dosing recommendations.

Adults: The usual adult dosage for guaifenesin is 200-400 mg every 4 hours as needed, not exceeding 2.4 g in 24 hours.

Mechanism of action

Guaifenesin is believed to work by increasing mucus secretion and acting as an irritant to gastric vagal receptors, which stimulates efferent parasympathetic reflexes. This leads to glandular exocytosis of less viscous mucus. Additionally, it may enhance respiratory tract fluid, thereby reducing the viscosity of secretions and improving ciliary action for more efficient mucus clearance.

Pharmacodynamics

As an expectorant, guaifenesin enhances the output of bronchial secretions and phlegm by decreasing their adhesiveness and surface tension. This results in an increased flow of less viscous gastric secretions, promoting ciliary action and converting unproductive coughs into more productive ones. Although it may also exhibit mild anticonvulsant and muscle relaxant properties, these effects are less well established.

Pharmacokinetics

Guaifenesin is rapidly absorbed from the gastrointestinal tract and reaches peak plasma concentrations within one hour of administration. It is metabolized in the liver, and its elimination half-life is approximately one hour. The drug is primarily excreted in the urine, mostly as metabolites.

Adverse effects

• Nausea
• Vomiting
• Dizziness
• Headache
• Rash

Precautions

• Use with caution in patients with chronic cough due to asthma, smoking, or emphysema
• Ensure adequate hydration while using

Pregnancy

Guaifenesin is categorized as pregnancy category C. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Guaifenesin is excreted in breast milk. Caution should be exercised when administered to breastfeeding women.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Oral syrup
• Tablets
• Extended-release capsules

Indications

• Insecticide for agricultural use
• Research tool in toxicology

Dosage

Children: Refer to the BNF for Children for specific dosing and administration guidelines.

Adults: Refer to the BNF for specific dosing and administration guidelines.

Mechanism of action

Methyl parathion acts primarily by inhibiting the enzyme acetylcholinesterase, which is essential for the breakdown of the neurotransmitter acetylcholine. Its active metabolite, methyl paraoxon, is a potent inhibitor of both acetylcholinesterase and butyrylcholinesterase. The inhibition of these enzymes results in the accumulation of acetylcholine at synapses, leading to overstimulation of cholinergic receptors and resultant toxic effects.

Pharmacodynamics

The pharmacodynamics of methyl parathion involve its action as a noncompetitive inhibitor of acetylcholinesterase, causing prolonged effects of acetylcholine due to its inability to be hydrolyzed. The resultant cholinergic toxicity can lead to symptoms such as muscle twitching, respiratory distress, and potentially fatal outcomes if not treated promptly. The extent of inhibition is dose-dependent, with significant toxicity occurring after substantial enzyme inhibition.

Pharmacokinetics

Methyl parathion is absorbed through the gastrointestinal tract and can also be absorbed through the skin and respiratory tract. It is metabolized in the liver to form methyl paraoxon, which is responsible for the majority of its toxic effects. The distribution of methyl parathion in body tissues is influenced by its lipophilicity, and it is primarily excreted as metabolites in the urine. The elimination half-life and specific pharmacokinetic parameters can vary based on individual metabolism and exposure levels.

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether this drug is excreted in human milk. Caution is advised when administering to nursing women.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Liquid formulation

Indications

• Topical analgesic for muscle and joint pain
• Cough suppressant in cough drops and lozenges
• Relief of minor throat irritation
• Cooling agent in various cosmetic and personal care products

Dosage

Children: Refer to BNF for Children for specific dosing guidelines, as doses may vary based on age and formulation.

Adults: For topical use, apply a thin layer to the affected area not more than 3 to 4 times daily. For cough drops, follow the product-specific instructions as per the formulation.

Mechanism of action

Menthol acts as an agonist for the transient receptor potential subtype M8 (TRPM8), a non-selective cation channel that is activated by cold temperatures. This activation leads to calcium influx in mast cells, inducing the release of histamine, which can trigger allergic responses such as urticaria, asthma, and rhinitis. Menthol's ability to induce histamine release via TRPM8 suggests potential therapeutic applications for TRPM8 antagonists in managing cold- and menthol-induced allergies.

Pharmacodynamics

Menthol produces a cooling effect by stimulating sensory neurons that convey cold sensations. It interacts with TRPM8 channels, leading to the activation of intracellular signaling pathways that can result in vasodilation and increased blood flow to the area of application. This cooling sensation can provide symptomatic relief in conditions characterized by pain or irritation.

Pharmacokinetics

Menthol is absorbed through the skin and mucous membranes, with systemic effects depending on the route of administration. Its bioavailability can vary, and it is metabolized primarily in the liver. The elimination half-life and excretion pathways have not been extensively characterized, but menthol is generally considered to have a rapid onset of action with effects lasting for a few hours.

Adverse effects

• Allergic reactions
• Urticaria
• Asthma
• Rhinitis
• Skin irritation

Precautions

• Use with caution in patients with known allergies to menthol or related compounds
• May exacerbate asthma in sensitive individuals

Pregnancy

There are no well-controlled studies of menthol in pregnant women. Menthol should be used during pregnancy only if clearly needed.

Breast-feeding

Menthol is excreted in breast milk. Caution should be exercised when administering to nursing mothers.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Topical ointment
• Cream
• Liquid

Indications

• Digestive aid
• Anti-inflammatory treatment
• Support for wound healing
• Sinusitis relief
• Potential adjunct in cardiovascular health

Dosage

Children: Pediatric dosing for bromelain is not well established. It is important to consult with a healthcare professional for appropriate dosing in children.

Adults: The typical dosage of bromelain supplements varies, but is often in the range of 200 to 400 mg taken 2 to 3 times daily. It is advisable to refer to specific product labels and consult healthcare professionals for personalized dosing recommendations.

Mechanism of action

Bromelain, the primary active compound in pineapple, exerts its effects by breaking down proteins into amino acids and peptides. This proteolytic activity is thought to facilitate digestion and reduce inflammation. Additionally, bromelain may enhance the absorption of certain antibiotics and other medications by improving gastrointestinal tract conditions.

Pharmacodynamics

Bromelain has shown anti-inflammatory, analgesic, and antithrombotic effects. It may modulate immune responses, reduce swelling, and promote healing. The pharmacodynamic properties of pineapple are largely attributed to bromelain, which acts on various pathways, including the modulation of cytokine production and inhibition of pro-inflammatory mediators.

Pharmacokinetics

Bromelain is rapidly absorbed in the gastrointestinal tract following oral administration. The bioavailability of bromelain can be affected by food intake, with some studies suggesting that it is best absorbed on an empty stomach. The elimination half-life is not well-defined, but its effects can persist due to its interactions with various biological pathways.

Adverse effects

• Allergic reactions in sensitive individuals
• Diarrhea
• Nausea
• Abdominal pain
• Heartburn

Interactions

• May interact with anticoagulants due to bromelain content
• Potential interaction with certain antibiotics
• Can affect the metabolism of some drugs due to effects on cytochrome P450 enzymes

Precautions

• Use with caution in individuals with known allergies to pineapple or bromelain
• Should be used cautiously in individuals with gastrointestinal disorders
• Consider potential interactions with anticoagulant medications

Pregnancy

Generally considered safe in food amounts, but high doses or supplements should be avoided due to potential uterine contractions.

Breast-feeding

Likely safe in food amounts; however, high doses or supplements should be avoided as effects are not well studied.

Storage

Store in a cool, dry place away from direct sunlight. Fresh pineapple should be refrigerated and consumed promptly.

Formulations

• Fresh pineapple
• Canned pineapple
• Pineapple juice
• Bromelain supplements

Dosage

Children: Refer to specific formulations and guidelines, as ponceau is primarily a colorant and not used therapeutically.

Adults: Refer to specific formulations and guidelines, as ponceau is primarily a colorant and not used therapeutically.

Mechanism of action

Ponceau exerts its color properties through the presence of azo groups (-N=N-), which absorb specific wavelengths of light, thereby producing a bright red color. The mechanism of action in terms of pharmacological effects is not well-defined, as ponceau is primarily a colorant rather than a pharmacologically active agent.

Pharmacodynamics

Ponceau does not have pharmacodynamic effects traditionally associated with therapeutic drugs, as it is not intended to exert a pharmacological effect. Its primary role is as a color additive, and any physiological response is typically limited to allergic reactions in susceptible individuals. The dye's interaction with biological systems is largely related to its structural properties rather than specific pharmacological activity.

Pharmacokinetics

The pharmacokinetics of ponceau are not well-studied, as it is mainly used as a colorant rather than a therapeutic agent. Generally, colorants like ponceau are not absorbed significantly in the gastrointestinal tract and are excreted unchanged. However, in cases of hypersensitivity or allergic reactions, the body's response may vary based on individual metabolism and immune response.

Pregnancy

There is limited data on the safety of ponceau in pregnancy. It should only be used if clearly needed and the potential benefits outweigh the risks.

Breast-feeding

It is unknown if ponceau is excreted in human milk. Caution should be exercised when administering to breastfeeding women.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Indications

• Plant growth regulation
• Agricultural applications as a growth inhibitor

Dosage

Children: Not applicable.

Adults: Refer to the relevant agricultural guidelines for specific applications.

Mechanism of action

In an in vitro study, propylene acts as a plant growth inhibitor by inhibiting the oxidation of indole-3-acetic acid by peroxidase in the presence of superoxide anion radicals. This inhibition is linked to the activation of an iron complex (compound III) shuttle, which enhances the reaction rate between superoxide and peroxidase, ultimately affecting plant growth processes. Propylene is a less effective inhibitor compared to ethylene.

Pharmacodynamics

The pharmacodynamic effects of propylene are primarily observed in its role as a growth inhibitor in plants. By modulating the oxidation of phytohormones like indole-3-acetic acid, propylene can influence various growth responses in plants, potentially affecting processes such as cell elongation and division.

Pharmacokinetics

Information on the pharmacokinetics of propylene in humans is not well-documented, as its primary uses are industrial and agricultural. Its metabolism may be influenced by environmental factors, and its effects are primarily studied in the context of plant biology rather than human pharmacology.

Dosage

Children: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Adults: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Mechanism of action

The mechanism of action for purified compounds varies widely depending on the specific substance. Generally, purified drugs exert their effects by interacting with specific biological targets, such as receptors, enzymes, or ion channels, leading to a desired therapeutic effect. This interaction can involve binding to receptors to activate or inhibit signaling pathways, modulating enzymatic activity, or altering physiological processes.

Pharmacodynamics

Pharmacodynamics describes the effects of a drug on the body and the relationship between drug concentration and effect. For purified drugs, this can involve dose-response relationships and the time course of their action. The purified form often enhances potency and reduces variability in response among patients, which can lead to more predictable therapeutic outcomes. The overall effect is determined by the drug's affinity for its target, the efficacy of the drug-receptor interaction, and the downstream signaling pathways activated as a result of this interaction.

Pharmacokinetics

Pharmacokinetics involves the absorption, distribution, metabolism, and excretion (ADME) of a drug. For purified substances, absorption can be more efficient due to the absence of impurities that may affect solubility or stability. Distribution may also be enhanced, leading to higher bioavailability. Metabolism can be influenced by the structure of the purified compound, as it may be metabolized more readily by liver enzymes. Excretion typically occurs through the kidneys or liver, depending on the molecular characteristics of the purified drug.

Pregnancy

Consult with a healthcare professional, as the safety of purified forms of medications during pregnancy may vary depending on the specific substance.

Breast-feeding

Consult with a healthcare professional, as the safety of purified forms of medications during breastfeeding may vary depending on the specific substance.

Storage

Store in a cool, dry place, away from light and moisture, and keep out of reach of children.

Indications

• Constipation
• Diagnostic aid in colonoscopy preparation
• Management of hyperosmolality in various conditions

Dosage

Children: For children, the dosage should be determined based on age and condition, and it is advised to refer to the BNF for Children for specific dosing guidelines.

Adults: The typical dose for adults is 30 to 150 mL of sorbitol solution (70%) taken orally, as needed, usually before bedtime.

Mechanism of action

Sorbitol exerts its laxative effect by drawing water into the large intestine, thereby stimulating bowel movements. It acts as a hygroscopic agent, pulling water from tissues into the feces, which reflexively stimulates evacuation. In metabolic pathways, sorbitol is produced from glucose via aldose reductase and is converted to fructose by sorbitol dehydrogenase, with implications in diabetic complications such as retinopathy.

Pharmacodynamics

Sorbitol's laxative effect results from its osmotic properties, which increase the water content of the stool and soften it, facilitating easier passage. Additionally, sorbitol can induce apoptosis in certain cancer cell lines, indicating potential therapeutic implications beyond its laxative use. The modulation of intracellular signaling pathways through the regulation of proteins such as Bax and Bcl-2 suggests a complex role in cellular health and disease.

Pharmacokinetics

Sorbitol is poorly absorbed in the gastrointestinal tract, which contributes to its efficacy as a laxative. It is metabolized in the liver, primarily through the polyol pathway. The absorption and distribution of sorbitol are affected by its osmotic properties, leading to increased intestinal water retention. Its elimination is primarily via renal excretion, with minimal systemic absorption, thus reducing the risk of systemic side effects.

Adverse effects

• Diarrhea
• Abdominal cramps
• Nausea
• Vomiting
• Electrolyte imbalances

Precautions

• Use with caution in patients with renal impairment
• May exacerbate gastrointestinal conditions

Pregnancy

Sorbitol is generally considered safe during pregnancy, but should be used under medical supervision.

Breast-feeding

Sorbitol is excreted in breast milk in small amounts; consult a healthcare provider before use.

Storage

Store in a cool, dry place, away from direct sunlight.

Formulations

• Oral solution
• Syrup

Indications

• Caloric reduction in food and beverages
• Management of diabetes
• Weight management

Dosage

Children: Refer to the BNF for Children for specific guidelines on the use of sucralose in pediatric populations.

Adults: Sucralose is typically used in food and beverage products as a sweetener. There are no specific dosage recommendations for adults, as it is used according to taste preference and product formulation.

Mechanism of action

Sucralose acts as a positive allosteric modulator of the human sweet taste receptor. It interacts with the T1R taste receptor family, particularly enhancing the sweetness perception by binding to the hinge region of the receptor. This interaction induces a conformational change that stabilizes the active state of the receptor, increasing its responsiveness to sweet stimuli. This mechanism allows sucralose to mimic the taste of sugar without the associated caloric intake.

Pharmacodynamics

As a non-nutritive sweetener, sucralose does not undergo metabolic processing in the body, which means it does not contribute to energy intake. It provides intense sweetness at low concentrations, stimulating the sweetness receptors in the taste buds. The pharmacodynamic profile indicates minimal physiological effects beyond taste perception, making it suitable for dietary use without impacting blood glucose levels.

Pharmacokinetics

Sucralose is poorly absorbed in the gastrointestinal tract, with an estimated absorption rate of less than 15%. The majority of ingested sucralose is excreted unchanged in the urine. The elimination half-life is not well defined due to its minimal absorption, but it is generally considered to have a rapid clearance from the body. The pharmacokinetic properties support its use as a safe alternative to sugar for those managing caloric intake.

Pregnancy

Sucralose is generally considered safe during pregnancy, but it is recommended to consult a healthcare provider.

Breast-feeding

Sucralose is also considered safe during breastfeeding, although it is advisable to seek medical advice.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Granulated sucralose
• Liquid sucralose
• Tablets

Mechanism of action

When administered rectally, glycerin exerts a hygroscopic and/or local irritant action, drawing water from the tissues into the feces and reflexively stimulating evacuation. Glycerin decreases intraocular pressure by creating an osmotic gradient between the blood and intraocular fluid, causing fluid to move out of the aqueous and vitreous humors into the bloodstream. Glycerin (glycerol) and sorbitol are hyperosmotic laxatives. When administered rectally, glycerin and sorbitol exert a hygroscopic and/or local irritant action, drawing water from the tissues into the feces and reflexly stimulating evacuation. The extent to which the simple physical distention of the rectum and the hygroscopic and/or local irritant actions are responsible for the laxative effects of some of these drugs is not known. Only extremely high oral doses of sorbitol (25 g daily) or glycerin exert laxative action. /Glycerin/ decreases intraocular pressure by creating an osmotic gradient between the blood and intraocular fluid, causing fluid to move out of the aqueous and vitreous humors into the bloodstream. The physicochemical effects of a series of alkanols, alkanediols and glycerol on erythrocyte shape and hemolysis at 4 and 20 degrees C were examined. We calculated the dielectric constant of the incubation medium, Ds, and the dielectric constant of the erythrocyte membrane Dm in the presence of organic solutes. The ratio Ds/Dm = -38.48 at 20 degrees C defines the normal biconcave shape in a medium without hemolytic agents. A decrease in Ds/Dm favors externalization or internalization with consequent hemolysis. Alkanols and alkanediols convert biconcave erythrocytes into echinocytes, which is accompanied by an increase in the projected surface area. Glycerol converts biconcave erythrocytes into stomatocytes, which was accompanied by a marginal decrease in the projected surface area. Progressive externalization in alkanols and alkanediols or internalization in glycerol resulted in a decrease in the projected surface area and the formation of smooth spheres. The degree of shape change induced was related to the degree of hemolysis and the ratio Ds/Dm. A decrease in temperature reduced both the degree of shape change and hemolysis. .../Thus/ physicochemical toxicity may be a result of a temperature dependent hydrophobic interaction between the organic solutes and the membrane and is best interpreted by the ability of the solutes to change Ds and Dm.

Pharmacodynamics

Glycerin is commonly classified as an osmotic laxative but may act additionally or alternatively through its local irritant effects; it may also have lubricating and fecal softening actions. Glycerin suppositories usually work within 15 to 30 minutes.

Mechanism of action

180 to 200 times sweeter than sucrose, it is metabolized as a protein and its subsequent amino-acids used up in there respective mechanisms.

Pharmacodynamics

Aspartame (L-alpha-aspartyl-L-phenylalanine methyl ester) is a low-calorie sweetener used to sweeten a wide variety of low- and reduced-calorie foods and beverages, including low-calorie tabletop sweeteners. Aspartame is composed of two amino acids, aspartic acid and phenylalanine, as the methyl ester. Aspartic acid and phenylalanine are also found naturally in protein containing foods, including meats, grains and dairy products. Methyl esters are also found naturally in many foods such as fruits and vegetable and their juices. Upon digestion, aspartame breaks down into three components (aspartic acid, phenylalanine and methanol), which are then absorbed into the blood and used in normal body processes. Neither aspartame nor its components accumulates in the body. These components are used in the body in the same ways as when they are derived from common foods.

Mechanism of action

Inflammation of the airways, increased mucus secretion, and altered mucociliary clearance are the hallmarks of various diseases of the respiratory tract. Mucus clearance is necessary for lung health; bromhexine aids in mucus clearance by reducing the viscosity of mucus and activating the ciliary epithelium, allowing secretions to be expelled from the respiratory tract. Recent have studies have demonstrated that bromhexine inhibits the transmembrane serine protease 2 receptor (TMPRSS2) in humans. Activation of TMPRSS2 plays an important role in viral respiratory diseases such as influenza A and Middle East Respiratory Syndrome (MERS). Inhibition of receptor activation and viral entry by bromhexine may be effective in preventing or treating various respiratory illnesses, including COVID-19. In vitro studies have suggested the action of ambroxol (a metabolite of bromhexine) on the angiogensin-converting enzyme receptor 2 (ACE2), prevents entry of the viral envelope-anchored spike glycoprotein of SARS-Cov-2 into alveolar cells or increases the secretion of surfactant, preventing viral entry.

Pharmacodynamics

Bromhexine thins airway secretions, improving breathing and discomfort associated with thick mucus in airways associated with a variety of respiratory conditions.

Mechanism of action

Ethylene glycol is metabolized by alcohol dehydrogenase to glycoaldehyde, which is then metabolized to glycolic, glyoxylic, and oxalic acids. These acids, along with excess lactic acid are responsible for the anion gap metabolic acidosis. Oxalic acid readily precipitates with calcium to form insoluble calcium oxalate crystals. Tissue injury is caused by widespread deposition of oxalate crystals and the toxic effects of glycolic and glyoxylic acids.

Mechanism of action

Although the exact mechanism of action of guaifenesin may not yet be formally or totally elucidated, it is believed that expectorants like guaifenesin function by increasing mucus secretion. Moreover, it is also further proposed that such expectorants may also act as an irritant to gastric vagal receptors, and recruit efferent parasympathetic reflexes that can elicit glandular exocytosis that is comprised of a less viscous mucus mixture. Subsequently, these actions may provoke coughing that can ultimately flush difficult to access, congealed mucopurulent material from obstructed small airways to facilitate a temporary improvement for the individual. Consequently, while it is generally proposed that guaifenesin functions as an expectorant by helping to loosen phlegm (mucus) and thin bronchial secretions to rid the bronchial passageways of bothersome mucus and make coughs more productive, there has also been research to suggest that guaifenesin possesses and is capable of demonstrating anticonvulsant and muscle relaxant effects to some degree possibly by acting as an NMDA receptor antagonist. Guaifenesin is thought to act as an expectorant by increasing the volume and reducing the viscosity of secretions in the trachea and bronchi. Thus it may increase the efficiency of the cough reflex and facilitate removal of the secretions; however, objective evidence for this is limited and conflicting. By increasing respiratory tract fluid, guaifenesin reduces the viscosity of tenacious secretions and acts as an expectorant. Guaifenesin, a commonly used agent for the treatment of cough, is termed an expectorant since it is believed to alleviate cough discomfort by increasing sputum volume and decreasing its viscosity, thereby promoting effective cough. Despite its common usage, relatively few studies, yielding contrasting results, have been performed to investigate the action and efficacy of guaifenesin. To evaluate the effect of guaifenesin on cough reflex sensitivity. Randomized, double-blind, placebo-controlled trial. Fourteen subjects with acute viral upper respiratory tract infection (URI) and 14 healthy volunteers. On 2 separate days, subjects underwent capsaicin cough challenge 1 to 2 hr after receiving a single, 400-mg dose (capsules) of guaifenesin or matched placebo. Measurements and results: The concentration of capsaicin inducing five or more coughs (C(5)) was determined. Among subjects with URI, mean (+/- SEM) log C(5) after guaifenesin and placebo were 0.92 +/- 0.17 and 0.66 +/- 0.14, respectively (p = 0.028). No effect on cough sensitivity was observed in healthy volunteers. /The/ results demonstrate that guaifenesin inhibits cough reflex sensitivity in subjects with URI, whose cough receptors are transiently hypersensitive, but not in healthy volunteers. Possible mechanisms include a central antitussive effect, or a peripheral effect by increased sputum volume serving as a barrier shielding cough receptors within the respiratory epithelium from the tussive stimulus.

Pharmacodynamics

Guaifenesin is categorized as an expectorant that acts by enhancing the output of phlegm (sputum) and bronchial secretions via decreasing the adhesiveness and surface tension of such material. Furthermore, guaifenesin elicits an increased flow of less viscous gastric secretions that subsequently promote ciliary action - all actions that ultimately change dry, unproductive coughing to coughs that are more productive and less frequent. Essentially, by decreasing the viscosity and adhesiveness of such secretions, guaifenesin enhances the efficacy of mucociliary activity in removing accumulated secretions from the upper and lower airway.

Mechanism of action

Acute poisoning ... is related to ... inhibiting action on enzyme acetylcholinesterase. Toxic manifestations generally occur only after more than 50% of plasma cholinesterase is inhibited. ... Methyl parathion ... depend on oxidative activation by replacement of thiono-sulfur with oxygen for ... toxicity. Methyl parathion has only a slight inhibitory action on acetylcholinesterase and butyrylcholinesterase, but its active metabolite, methyl paraoxon, is a potent inhibitor of both these enzymes. A study was conducted examining the inhibition of (Ca2+ and Mg2+)-ATPase by parathion (56382) and methyl parathion. Enzyme activity was assessed spectrophotometrically in pig erythrocyte membranes containing calcium2+ (Ca2+) and magnesium2+ and in solubilized membrane preparations incubated with the test agents. The enzyme response to ATP was biphasic. Equations expressing the kinetics of the substrate curves described two classes of the ATP binding active site, one with high affinity and low maximum rate and one with low affinity and high maximum rate. High affinity active sites were stimulated by low ATP concentrations (20 uM), whereas low affinity active sites were stimulated by high ATP levels (2 mM). Parathion and methylparathion dose dependently inhibited enzyme activity; parathion had a greater inhibitory effect than methylparathion. Lineweaver-Burke and Dixon plots indicated noncompetitive inhibition. Parathion and methylparathion induced enzyme inhibition occurred over a range of free calcium ion concentrations (0.5 to 5 mM); the inhibition was significantly greater at lower Ca2+ concentrations (1 to 100 uM) than at higher concentrations. The authors conclude that parathion and methylparathion inhibit ATPase activity by binding to a site on the enzyme rather than through an interaction with associated lipids. For more Mechanism of Action (Complete) data for METHYL PARATHION (6 total), please visit the HSDB record page.

Mechanism of action

Exposure to low temperatures often causes allergic responses or urticaria. Similarly, menthol, a common food additive is also known to cause urticaria, asthma, and rhinitis. However, despite the obvious clinical implications, the molecular mechanisms responsible for inducing allergic responses to low temperatures and menthol have not been determined. Because a non-selective cation channel, transient receptor potential subtype M8 (TRPM8) is activated by cold and menthol, we hypothesized that this channel mediates cold- and menthol-induced histamine release in mast cells. Here, we report that TRPM8 is expressed in the basophilic leukemia mast cell line, RBL-2H3, and that exposure to menthol or low temperatures induced Ca(2+) influx in RBL-2H3 cells, which was reversed by a TRPM8 blocker. Furthermore, menthol, a TRPM8 agonist, induced the dose-dependent release of histamine from RBL-2H3 cells. When TRPM8 transcripts were reduced by siRNA (small interfering RNA), menthol- and cold-induced Ca(2+) influx and histamine release were significantly reduced. In addition, subcutaneous injection of menthol evoked scratching, a typical histamine-induced response which was reversed by a TRPM8 blocker. Thus, our findings indicate that TRPM8 mediates the menthol- and cold-induced allergic responses of mast cells, and suggest that TRPM8 antagonists be viewed as potential treatments for cold- and menthol-induced allergies. /DL-Menthol/ Menthol's characteristic cooling sensation is due, in part, to the activation of sensory neurons generally termed transient receptor potential (TRP) channels, in particular transient receptor potential melastatin family member 8 (TRPM8) and transient receptor potential subfamily A, member 1 (TRPA1). Menthol acts upon TRPM8 receptors by rapidly increasing intracellular calcium and mobilizing calcium flux through the channels to induce cold response signals at the application site. Aside from its cold-inducing sensation capabilities, menthol exhibits cytotoxic effects in cancer cells, induces reduction in malignant cell growth, and engages in synergistic excitation of GABA receptors and sodium ion channels resulting in analgesia. /DL-Menthol/ In recent years, the transient receptor potential melastatin member 8 (TRPM8) channel has emerged as a promising prognostic marker and putative therapeutic target in prostate cancer. We have found that forced overexpression of TRPM8 in PC-3 cells can inhibit the cell proliferation and motility probably through the TRPM8 activation. In this study, we aimed to investigate whether activating the TRPM8 channel by its selective agonist menthol can inhibit the proliferation and motility of androgen-independent prostate cancer (AIPC) with remarkable expression of TRPM8. Menthol is a naturally occurring compound, which has been widely used in cosmetics and pharmaceutical products, and also as flavoring in food. DU145 cells are androgen-independent but have a remarkable expression of TRPM8. The demonstration of the existence of TRPM8 and the absence of TRPA1 in DU145 cells provided the foundation for the following experiments, because both TRPM8 and TRPA1 are molecular targets of menthol. The outcome of MTT assay indicated that menthol inhibited the cell growth (p < 0.01). Cell cycle distribution and scratch assay analysis revealed that menthol induced cell cycle arrest at the G(0)/G(1) phase (p < 0.01). Furthermore, menthol inhibited the migration of DU145 cells by downregulating the focal-adhesion kinase. So it suggests that the activation of the existing TRPM8 channels may serve as a potential and pragmatic treatment for those AIPC with remarkable expression of TRPM8, and menthol is a useful compound for future development as an anticancer agent. /DL-Menthol/

Mechanism of action

In an in vitro study of the mechanism of action of ethylene as a plant growth inhibitor, the effects of ethylene and some of its analogs, including propylene, on the oxidation of indole-3-acetic acid were examined. Ethylene and its analogs inhibited the oxidation of indole-3-acetic acid by peroxidase under conditions where the iron complex (compound III, an oxy-ferrous complex of peroxidase) shuttle was activated. Inhibition occurred only in the presence of the superoxide anion radical 02(-). Spectral and kinetic data indicated that ethylene and its analogs enhanced the rate of reaction of 02(-) with peroxidase; ie, the iron complex (compound III) shuttle, resulting in the formation of compound III. Propylene was a less effective inhibitor than ethylene.

Mechanism of action

Sorbitol exerts its laxative effect by drawing water into the large intestine, thereby stimulating bowel movements. ... Sorbitol exerts hygroscopic and/or local irritant action, drawing water from tissues into feces and reflexly stimulating evacuation. The polyol pathway consists of two enzymes aldose reductase (AR) and sorbitol dehydrogenase (SDH); the former is the first enzyme in the polyol pathway, that catalyzes the reduction of glucose to sorbitol, the latter is the second one, that converts sorbitol to fructose using by NAD(+) as a cofactor. ... SDH activity, the second step in the polyol pathway, might make a greater contribution to the etiology of diabetic retinopathy than does the first step involving AR. /This paper proposes/ a novel hypothesis that polymorphisms of SDH gene may be correlated with SDH gene expression levels in diabetic retinas, thus being a valuable genetic marker for diabetic retinopathy. It has been reported that sorbitol induces apoptosis in several cancer cell lines. ... In /this/ study, the intracellular signaling pathways of sorbitol-induced apoptosis in human K562 cells were investigated using both morphological analysis and DNA fragmentation technique. In this study, we demonstrated that sorbitol-induced apoptosis in human K562 cells is a concentration- and time-dependent manner. This sorbitol-induced apoptosis in human K562 cells was also accompanied by the up-regulation of Bax, and down-regulation of p-Bcl-2, but no effect on the levels of Bcl-X(L). Moreover, the sorbitol treatment resulted in a significant reduction of mitochondria membrane potential, increase in the release of mitochondrial cytochrome c (cyt c), and activation of caspase 3. Furthermore, treatment with caspase 3 inhibitor (z-DEVD-fmk) was capable of preventing the sorbitol-induced caspase 3 activity and cell death. These results clearly demonstrate that the induction of apoptosis by sorbitol involves multiple cellular/molecular pathways and strongly suggest that pro- and anti-apoptotic Bcl-2 family proteins, mitochondrial membrane potential, mitochondrial cyt c, and caspase 3, they all participate in sorbitol-induced apoptotic process in human K562 cells. Chronic diabetic complications, in particular, nephropathy, peripheral and autonomic neuropathy, "diabetic foot," retinopathy, and cardiovascular disease, remain the major cause of morbidity and mortality in patients with diabetes mellitus. Growing evidence indicates that both increased activity of the sorbitol pathway of glucose metabolism and enhanced oxidative stress are the leading factors in the pathogenesis of diabetic complications. The relation between the two mechanisms remains the area of controversy. One group has reported that increased sorbitol pathway activity has a protective rather than detrimental role in complication-prone tissues because the pathway detoxifies toxic lipid peroxidation products. Others put forward a so-called "unifying hypothesis" suggesting that activation of several major pathways implicated in diabetic complications (eg, sorbitol pathway) occurs due to increased production of superoxide anion radicals in mitochondria and resulting poly(ADP-ribose) polymerase activation. This review (a) presents findings supporting a key role for the sorbitol pathway in oxidative stress and oxidative stress-initiated downstream mechanisms of diabetic complications, and (b) summarizes experimental evidence against a detoxifying role of the sorbitol pathway, as well as the "unifying concept."

Mechanism of action

Positive allosteric modulators of the human sweet taste receptor ...developed as a new way of reducing dietary sugar intake .../can be used as/ ...valuable tool molecules to study the general mechanism of positive allosteric modulations of T1R taste receptors. Using chimeric receptors, mutagenesis, and molecular modeling, .../the study/ reveal how ...sweet enhancers follow a similar mechanism as the natural umami taste enhancer molecules. Whereas the sweeteners bind to the hinge region and induce the closure of the Venus flytrap domain of T1R2, the enhancers bind close to the opening and further stabilize the closed and active conformation of the receptor.