Listerine Smart Rinse Mild Mint

Indications

• Methemoglobinemia
• Urinary tract infections
• Surgical marking
• Treatment of certain types of cyanide poisoning

Dosage

Children: Refer to the BNF for Children for appropriate pediatric dosing information.

Adults: Refer to the relevant clinical guidelines or the BNF for specific dosing recommendations.

Mechanism of action

Methylene blue acts as a reducing agent, converting methemoglobin back to its functional form, hemoglobin. This is primarily achieved through its action as an electron donor, facilitating the reduction of ferric iron (Fe3+) in hemoglobin to ferrous iron (Fe2+), thereby restoring its oxygen-carrying capacity. It also exhibits antimicrobial properties through its ability to generate reactive oxygen species when exposed to light, which can inhibit bacterial growth.

Pharmacodynamics

The pharmacodynamics of methylene blue involve its role in enhancing oxygen delivery in patients suffering from methemoglobinemia. By converting methemoglobin back to hemoglobin, it effectively increases the amount of hemoglobin available for oxygen transport. The drug also shows effects on the vascular system, where it can induce vasodilation and influence blood pressure.

Pharmacokinetics

Methylene blue is rapidly absorbed after intravenous administration, with peak plasma concentrations occurring within 1 to 3 hours. It is extensively distributed in body tissues and fluids, including the liver, kidneys, and lungs. The drug undergoes hepatic metabolism, primarily through the cytochrome P450 system, and is excreted mainly through urine. The half-life ranges from 5 to 24 hours, depending on the dosage and individual patient factors.

Pregnancy

Consult healthcare provider before use, as safety in pregnancy is not established.

Breast-feeding

Consult healthcare provider before use, as safety during breastfeeding is not established.

Storage

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

Indications

• Oral hygiene
• Prevention of dental plaque
• Management of minor infections in the oral cavity

Dosage

Children: Refer to BNF for Children for appropriate formulations and guidance on paediatric use.

Adults: Refer to BNF for specific formulations and usage instructions. Typical concentrations in mouthwashes are around 0.05% to 0.1%.

Mechanism of action

Cetylpyridinium chloride functions as a cationic surfactant that interacts with microbial cell surfaces due to its positively charged hydrophilic region. This interaction disrupts bacterial membrane integrity, leading to leakage of cytoplasmic components, interference with cellular metabolism, and ultimately, cell death. Additionally, it inhibits the synthesis of insoluble glucan by streptococcal glucosyltransferase, adsorbs to enamel surfaces, and prevents bacterial co-adhesion, enhancing its effectiveness in oral hygiene.

Pharmacodynamics

Cetylpyridinium chloride exhibits rapid bactericidal effects against gram-positive pathogens and fungicidal activity against yeasts. It is classified as a cationic disinfectant with local effects, making it suitable for managing minor infections. Its surfactant properties contribute to its efficacy in reducing microbial load in oral care applications.

Pharmacokinetics

Cetylpyridinium chloride is characterized by poor systemic absorption when used topically; therefore, its effects are primarily local rather than systemic. This property allows it to exert its antimicrobial action in the mouth without significant absorption into the bloodstream, making it safe for use in oral care products.

Adverse effects

• Mouth irritation
• Taste alteration
• Dryness of the mouth
• Nausea
• Diarrhea

Precautions

• Use with caution in individuals with a history of hypersensitivity to cetylpyridinium chloride or other quaternary ammonium compounds.
• Avoid swallowing the product.
• Not recommended for use in children under a certain age without medical advice.

Pregnancy

Cetylpyridinium chloride should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consultation with a healthcare provider is advised.

Breast-feeding

It is not known whether cetylpyridinium chloride is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

Store at room temperature, away from direct sunlight and moisture. Keep out of reach of children.

Formulations

• Mouthwash
• Toothpaste
• Lozenges
• Mouth sprays

Indications

• Fever
• Pain relief
• Inflammation
• Skin irritation
• Muscle aches

Dosage

Children: Refer to specific product guidelines or the BNF for Children, as pediatric dosing varies with age and weight.

Adults: Refer to specific product guidelines as doses can vary based on the formulation and condition being treated.

Mechanism of action

The cooling effect of certain medications such as menthol is primarily due to its ability to activate the TRPM8 (transient receptor potential cation channel subfamily M member 8) receptors, which are involved in the sensation of coolness. This receptor activation leads to the perception of cooling on the skin or mucous membranes. In the case of antipyretics like paracetamol, the mechanism involves inhibition of the cyclooxygenase (COX) enzymes, leading to reduced prostaglandin synthesis and subsequently lowering fever.

Pharmacodynamics

Medications with cooling effects often produce their effects by local vasodilation, which increases blood flow to the area, facilitating a sensation of cooling. In the case of antipyretics, their pharmacodynamic effects include decreased prostaglandin production in the brain, resulting in lowered set-point temperature in the hypothalamus. This leads to an overall reduction in fever and alleviation of associated symptoms.

Pharmacokinetics

The pharmacokinetics of cooling agents such as menthol involve rapid absorption through the skin and mucous membranes, with peak effects typically occurring shortly after application. For systemic antipyretics like paracetamol, absorption occurs primarily in the gastrointestinal tract, with a bioavailability of approximately 70-90%. Metabolism occurs primarily in the liver, and elimination is primarily via renal excretion. The half-life of paracetamol is typically around 2-4 hours.

Pregnancy

Consult a healthcare provider before use, as safety during pregnancy has not been established.

Breast-feeding

Consult a healthcare provider before use, as safety during breastfeeding has not been established.

Storage

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

Dosage

Children: Refer to specific formulations and clinical guidelines for dosing information as this can vary widely based on the context of use.

Adults: Refer to specific formulations and clinical guidelines for dosing information as this can vary widely based on the context of use.

Mechanism of action

Dibasic compounds often act by providing a buffering effect in biological systems, which helps to maintain physiological pH levels. They may also interact with various biological targets depending on their specific structure, influencing metabolic pathways and cellular functions.

Pharmacodynamics

The pharmacodynamics of dibasic compounds is highly variable and depends on their specific chemical structure and the context of their use. Generally, these compounds may alter the absorption and distribution of other drugs, modulate enzyme activity, or affect cellular signaling pathways through their interactions with biological molecules.

Pharmacokinetics

The pharmacokinetics of dibasic compounds can vary widely. Factors such as solubility, stability, and route of administration influence their absorption, distribution, metabolism, and excretion. Typically, dibasic compounds may be absorbed in the gastrointestinal tract and may undergo various metabolic processes depending on their specific nature.

Pregnancy

Dibasic compounds should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult with a healthcare provider.

Breast-feeding

Caution is advised when administering dibasic compounds to breastfeeding mothers. Consult with a healthcare provider.

Storage

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

Indications

• Prevention of dental caries
• Treatment of dental hypersensitivity
• Topical application for high caries risk patients

Dosage

Children: Refer to the BNF for Children for specific paediatric dosage recommendations, which are typically based on age and dental health needs.

Adults: Refer to the BNF for specific adult dosage recommendations, which may vary based on the formulation and indication.

Mechanism of action

Fluoride acts primarily by enhancing the mineralization process of the tooth enamel through the formation of fluorapatite, which is more resistant to acid dissolution than hydroxyapatite. It also inhibits the activity of specific enzymes in bacteria that contribute to acid production, thereby reducing the overall cariogenic potential of dental plaque.

Pharmacodynamics

Fluoride exhibits a dose-dependent effect on dental health, with low concentrations promoting enamel remineralization and higher concentrations potentially toxic to bacteria. Its effectiveness is attributed to its ability to integrate into the crystalline structure of teeth, leading to improved resistance to acid attacks. Additionally, fluoride can modulate the metabolism of oral bacteria, reducing their ability to produce acid from fermentable carbohydrates.

Pharmacokinetics

Fluoride is readily absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 1 to 2 hours after ingestion. It is distributed throughout the body, with significant accumulation in bones and teeth. The elimination half-life varies, but fluoride is primarily excreted unchanged via the kidneys. The clearance rate can be influenced by renal function as well as dietary factors.

Pregnancy

Fluoride is generally considered safe during pregnancy when used in appropriate doses for dental health. However, excessive intake should be avoided.

Breast-feeding

Fluoride is excreted in breast milk in small amounts. It is generally regarded as safe for breastfeeding mothers when used appropriately.

Storage

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

Indications

• Pain relief
• Anti-inflammatory treatment
• Antipyretic therapy
• Nutritional supplementation
• Electrolyte replacement
• Treatment of gastrointestinal disorders

Dosage

Children: Refer to specific product labeling or clinical guidelines for paediatric dosing, as this varies widely depending on the active ingredient and condition being treated.

Adults: Refer to specific product labeling or clinical guidelines for adult dosing, as this varies widely depending on the active ingredient and condition being treated.

Mechanism of action

The mechanism of action for granular formulations depends on the active pharmaceutical ingredient contained within the granules. Generally, these medications may work by various mechanisms such as inhibiting certain enzymes, blocking receptors, or modulating specific pathways involved in disease processes. For example, if the granules contain a medication that acts as an anti-inflammatory, it may inhibit the cyclooxygenase (COX) enzymes involved in the production of inflammatory mediators.

Pharmacodynamics

Pharmacodynamics describes how a drug affects the body. Granular medications can provide a rapid onset of action due to their surface area, which facilitates quicker dissolution and absorption. The effects vary depending on the active ingredient, which may influence various biological pathways, such as neurotransmitter modulation, receptor activation, or inhibition of certain cellular processes. The therapeutic effects are often dose-dependent and can be influenced by factors such as age, weight, and overall health.

Pharmacokinetics

The pharmacokinetics of granular formulations also vary based on the specific active ingredient. Generally, pharmacokinetic parameters include absorption, distribution, metabolism, and excretion (ADME). Granular medications typically exhibit faster absorption compared to solid dosage forms due to the larger surface area. Distribution will depend on factors like solubility and protein binding. Metabolism primarily occurs in the liver, while excretion can take place via the kidneys or bile, again depending on the nature of the active compound.

Pregnancy

Safety during pregnancy has not been established. Use only if clearly needed and potential benefits justify the risks.

Breast-feeding

Use with caution. Limited data available, and effects on the nursing infant are unknown.

Storage

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

Dosage

Children: Refer to the relevant guidelines for specific dosing information.

Adults: Refer to the relevant guidelines for specific dosing information.

Pregnancy

Safety during pregnancy has not been established. Use only if clearly needed and the benefits outweigh the risks.

Breast-feeding

It is not known whether this drug is excreted in human milk. Caution is advised.

Storage

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

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 issues
• Nausea
• Headaches
• Respiratory conditions
• Oral hygiene
• Muscle pain relief

Dosage

Children: Dosage should be determined based on age and formulation. Consult specific product instructions and healthcare providers.

Adults: Dosage varies based on preparation and indication. For herbal formulations, refer to specific product guidelines.

Mechanism of action

The active compounds in mint, particularly menthol and menthone, exert their effects primarily through activation of the TRPM8 receptor, which is a cold and menthol receptor. This activation induces a cooling sensation and may provide analgesic effects. Menthol also acts as a smooth muscle relaxant, which can help alleviate gastrointestinal discomfort.

Pharmacodynamics

Mint exhibits various pharmacological effects, including carminative, antispasmodic, and mild analgesic properties. It is known to enhance gastric motility and reduce symptoms of irritable bowel syndrome (IBS). The menthol component may also exhibit mild anti-inflammatory properties and has been used in topical formulations for its cooling and soothing effects.

Pharmacokinetics

After ingestion, mint compounds are rapidly absorbed in the gastrointestinal tract. Menthol is metabolized primarily in the liver, undergoing conjugation. The elimination half-life of menthol is roughly 1-3 hours. The compounds are excreted mainly through urine, with a small percentage being exhaled as volatile constituents.

Adverse effects

• Allergic reactions
• Gastrointestinal disturbances
• Heartburn
• Headaches

Interactions

• May interact with medications that affect the liver enzymes responsible for its metabolism
• Potential interaction with antacids

Precautions

• Use with caution in individuals with gastroesophageal reflux disease (GERD)
• May cause allergic reactions in sensitive individuals

Pregnancy

Generally considered safe when used in food amounts. High doses should be avoided due to potential effects on uterine tone.

Breast-feeding

Generally safe in usual dietary amounts. Consult healthcare provider for concentrated supplements.

Storage

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

Formulations

• Fresh leaves
• Dried leaves
• Essential oil
• Teas

Indications

• Hypophosphatemia
• Calcium phosphate deficiency
• Nutritional supplementation
• pH adjustment in pharmaceutical formulations

Dosage

Children: Refer to BNF for Children for specific dosing recommendations based on indication.

Adults: Refer to clinical guidelines or BNF for specific dosing recommendations based on indication.

Mechanism of action

Phosphoric acid provides phosphate ions that are critical for numerous biochemical reactions in the body. These phosphate ions are involved in the formation of ATP, which is essential for energy transfer within cells. The acid itself dissociates in aqueous solutions, releasing hydrogen ions and contributing to pH levels, which can affect enzymatic activities and cellular functions.

Pharmacodynamics

Phosphoric acid acts by replenishing phosphate levels in the body, which can be important in various physiological processes including energy metabolism, bone mineralization, and the synthesis of nucleic acids. Its effects on pH regulation can also influence metabolic pathways, particularly in managing acidosis or alkalosis.

Pharmacokinetics

Phosphoric acid is generally administered orally or intravenously, depending on the therapeutic application. Following administration, it is absorbed in the gastrointestinal tract, with phosphate ions distributed throughout the body. The kidneys play a significant role in regulating phosphate homeostasis, with excess phosphate being excreted in urine. The half-life of phosphoric acid is not well defined, as it is rapidly metabolized and utilized in various metabolic pathways.

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Hypophosphatemia

Precautions

• Use with caution in patients with renal impairment
• Monitor phosphate levels in patients receiving long-term therapy
• Consider potential for gastrointestinal irritation

Pregnancy

Phosphoric acid is generally considered safe in pregnancy when used in recommended doses, but caution is advised.

Breast-feeding

Phosphoric acid is excreted in breast milk, use with caution and under medical supervision.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Oral solutions
• Tablets
• Syrups

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

Pregnancy

No specific data available, consult a healthcare professional.

Breast-feeding

No specific data available, consult a healthcare professional.

Storage

Store in a cool, dry place away from light.

Mechanism of action

When incorporated into mouthwashes, toothpastes, lozenges, or mouth sprays, cetylpyridinium chloride is expected to elicit a mechanism of action that decreases new dental plaque growth, decreases or removes existing dental plaque, diminishes the growth of pathogenic bacteria, and inhibits the production of virulence factors. Cetylpyridinium chloride is a quaternary ammonium compound that demonstrates a broad spectrum anti-bacterial activity. It possesses a cationic surface active agent surfactant which can absorb readily to oral surfaces. The molecules of this agent have both hydrophilic and hydrophobic groups. In action, the positively charged hydrophilic region of cetylpyridinium chloride molecules enables the compound to interact with microbial cell surfaces and even integrate into the bacterial cytoplasmic membrane. Consequently, there is a resultant disruption of bacterial membrane integrity causing a leakage of bacterial cytoplasmic components, interference with cellular metabolism, inhibition of cell growth, and ultimately - cell death. Moreover, cetylpyridinium chloride can also inhibit the synthesis of insoluble glucan by streptococcal glucosyltransferase, adsorb to pellicle-covered enamel, and inhibit co-adhesion of bacteria, and bind streptococcus mutans biofilms. This ability of cetylpyridinium chloride to be able to adsorb to pellicle covered enamel imparts substantivity to the compound molecules - that is retention in the mouth and continued antimicrobial activity for a period of time after rinsing. Taking these mechanisms into consideration, cetylpyridinium chloride may be considered an active ingredient that is effective in the treatment and prevention of bacterial or fungal disorders of the oropharyngeal cavity.

Pharmacodynamics

Cetylpyridinium chloride is considered a cationic disinfectant with properties and uses similar to other such cationic surfactants. In particular, cetylpyridinium chloride has demonstrated a rapid bactericidal and fungicide effect on gram-positive pathogens and yeasts, respectively. Cetylpyridinium chloride is subsequently utilized in a variety of preparations for the local treatment of minor infections. Despite the variety of formulations in which cetylpyridinium chloride may appear as an active ingredient, it is generally accepted that it only elicits a local effect owing to the compound's relatively poor absorption by route of exposure.

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

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.