MIMS>PAIN>RUB COMBINATION PRODUCT OINTMENT

Indications

• Topical pain relief
• Muscle aches
• Joint pain
• Inflammation

Dosage

Children: For children, the

Adults: For topical application, camphor is usually applied as needed to the affected area, following the instructions on the specific product used. Consult the product label or a healthcare professional for detailed dosing guidelines.

Mechanism of action

Camphor activates the transient receptor potential vanilloid 1 (TRPV1) and TRPV3 channels, which are involved in sensing pain and temperature. It requires higher concentrations to activate TRPV1 compared to capsaicin but notably desensitizes TRPV1 more rapidly and completely. This action is enhanced under inflamed conditions through phospholipase C-coupled receptor stimulation. The distinct activation pathways of camphor contribute to its analgesic effects, making it effective in reducing pain sensitivity.

Pharmacodynamics

The pharmacodynamic properties of camphor are primarily related to its interaction with TRPV1 and TRPV3 channels. By activating these receptors, camphor induces a sensation of warmth and can result in analgesia through sensory nerve excitation and subsequent desensitization. This mechanism is similar to that of other topical analgesics like capsaicin and menthol but is characterized by a faster desensitization of TRPV1. Additionally, camphor's effects may include local vasodilation and increased blood flow to the area of application, which can further alleviate pain and inflammation.

Pharmacokinetics

Camphor is absorbed through the skin when applied topically. Its pharmacokinetic profile involves distribution to various tissues, where it can exert local effects. The metabolism of camphor occurs primarily in the liver, and it is eliminated from the body mainly through urine. The onset of action is typically rapid due to its topical application, and the duration of effect may vary depending on the formulation and concentration used.

Adverse effects

• Skin irritation
• Allergic reactions
• Nausea
• Vomiting
• Dizziness

Precautions

• Use with caution in individuals with sensitive skin
• Avoid contact with eyes and mucous membranes
• Do not apply to broken or irritated skin
• Keep out of reach of children

Pregnancy

Camphor should be used with caution during pregnancy. It is advisable to consult a healthcare professional before use.

Breast-feeding

Camphor should be used with caution while breastfeeding. Consult a healthcare professional for advice.

Storage

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

Formulations

• Topical ointments
• Liniments
• Creams
• Gels

Indications

• Anesthesia (historically)
• Induction of dissociative anesthesia
• Research purposes in neuropharmacology

Dosage

Children: There are no established pediatric dosages for PCP, and its use in children is not recommended.

Adults: Dosage should be guided by clinical context and individual response, as this substance is not used in standard medical practice due to its potential for abuse and adverse effects.

Mechanism of action

PCP binds to a site within the ion channel of the NMDA receptor, blocking the influx of positive ions such as calcium and sodium. This inhibition prevents neuronal depolarization and disrupts normal neurotransmission, leading to its psychoactive effects. Additionally, PCP's interaction with the GluN2D subunit of the NMDA receptor has implications for its impact on motor function.

Pharmacodynamics

Phencyclidine exhibits its primary effects through NMDA receptor antagonism, leading to decreased excitatory neurotransmission in the brain. This results in a range of behavioral and physiological changes, including dissociation, hallucinations, and altered sensory perceptions. The drug's effects are dose-dependent and can lead to significant motor impairment due to its action on the NMDA receptor pathways.

Pharmacokinetics

PCP is rapidly absorbed and distributed throughout the body. It has a relatively high volume of distribution and is primarily metabolized in the liver. The elimination half-life can vary significantly but is generally in the range of several hours. PCP is excreted mainly in urine, and its metabolites can be detected for a prolonged period after use.

Pregnancy

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

Breast-feeding

It is not known whether phencyclidine is excreted in human milk. Caution should be exercised when administered to a nursing woman.

Storage

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

Indications

• Respiratory infections
• Cough and cold symptoms
• Sinusitis
• Bronchitis
• Muscle pain and inflammation

Dosage

Children: Refer to specific product guidelines or consult a healthcare professional for appropriate dosing of eucalyptus oil in children, as it varies based on formulation and indication.

Adults: Refer to specific product guidelines or consult a healthcare professional for appropriate dosing of eucalyptus oil, as it varies based on formulation and indication.

Mechanism of action

Eucalyptus oil contains compounds such as eucalyptol (1,8-cineole) that exhibit antimicrobial properties. It acts on the respiratory system by promoting bronchodilation and reducing mucus production. The oil also has a cooling effect, which can provide relief from symptoms of respiratory distress. Additionally, the oil's anti-inflammatory properties help decrease inflammation in the airways.

Pharmacodynamics

The primary active ingredient in eucalyptus oil, eucalyptol, interacts with the body's inflammatory response and can modulate the activity of neurotransmitters involved in pain signaling. It may enhance mucociliary clearance in the respiratory tract, facilitating the expulsion of mucus and pathogens. The analgesic effects can help relieve discomfort associated with respiratory infections.

Pharmacokinetics

Eucalyptus oil is typically administered via inhalation or topical application. When inhaled, components like eucalyptol are absorbed through the mucous membranes of the respiratory tract and rapidly distributed throughout the body. The oil is metabolized primarily in the liver, and its metabolites are excreted in urine. The half-life of eucalyptol varies but is generally short, necessitating frequent dosing for sustained effects.

Adverse effects

• Allergic reactions
• Skin irritation
• Nausea
• Vomiting
• Diarrhea
• Dizziness

Interactions

• May interact with anticoagulants, potentially increasing bleeding risk
• May enhance the effects of other medications that cause sedation

Precautions

• Use with caution in individuals with asthma or other respiratory conditions
• Avoid use in young children without medical supervision
• Eucalyptus oil should not be ingested in large quantities due to toxicity

Pregnancy

Eucalyptus oil is generally considered unsafe in pregnancy due to potential toxicity and should be avoided unless prescribed by a healthcare professional.

Breast-feeding

Caution is advised when using eucalyptus during breastfeeding, as it may pass into breast milk and could affect the infant.

Storage

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

Formulations

• Eucalyptus oil (topical, inhalation, or oral preparations)
• Eucalyptus leaves (dried for teas or extracts)

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

• Allergic conditions
• Autoimmune diseases
• Asthma and chronic obstructive pulmonary disease (COPD)
• Certain cancers (e.g., leukemia, lymphoma)
• Skin conditions (e.g., dermatitis)
• Inflammatory bowel disease
• Multiple sclerosis exacerbations
• Severe infections requiring immunosuppression

Dosage

Children: Refer to BNF for Children for specific dosing; doses vary significantly based on the child's age, weight, and condition being treated.

Adults: Refer to BNF for specific dosing; typically, initial doses range from 4 to 48 mg depending on the severity of the condition.

Mechanism of action

Methylprednisolone exerts its effects by binding to glucocorticoid receptors, leading to the modulation of gene expression. This interaction influences the transcription of anti-inflammatory proteins while suppressing the expression of pro-inflammatory genes, ultimately resulting in reduced inflammation and immune response.

Pharmacodynamics

The pharmacodynamic effects of methylprednisolone are characterized by its ability to decrease inflammation, suppress the immune response, and affect carbohydrate metabolism. Therapeutic doses lead to various systemic effects, including modification of leukocyte distribution and inhibition of cytokine production.

Pharmacokinetics

Methylprednisolone is well absorbed after oral administration, with a bioavailability of approximately 50%. It has a volume of distribution that reflects extensive tissue binding. The drug is metabolized primarily in the liver through conjugation and reduction, and its metabolites are excreted in urine. The half-life varies based on the route of administration but is generally around 18 to 36 hours.

Adverse effects

• Increased blood pressure
• Hyperglycemia
• Weight gain
• Mood changes
• Insomnia
• Gastrointestinal disturbances
• Increased susceptibility to infections

Interactions

• methylphenidate+apraclonidine: Severe (decreases effects)
• methylthioninium chloride+bupropion: Severe (increases risk of severe hypertension)
• methylphenidate+linezolid: Severe (increases risk of elevated blood pressure)
• rasagiline+methylphenidate: Severe (increases risk of a hypertensive crisis)
• mao-inhibitors+methylphenidate: Severe (increases risk of a hypertensive crisis)
• dronedarone+methylprednisolone: Moderate (increases exposure)
• miconazole+methylprednisolone: Moderate (increases concentration)
• antifungals, azoles+methylprednisolone: Moderate (increases exposure)
• crizotinib+methylprednisolone: Moderate (increases exposure)

Precautions

• Use with caution in patients with hypertension
• Monitor blood glucose levels in diabetic patients
• Consider potential for infection risk due to immunosuppression
• Evaluate for psychiatric effects in susceptible individuals

Pregnancy

Corticosteroids may be used during pregnancy if the potential benefit justifies the risk to the fetus. Careful monitoring is advised.

Breast-feeding

Corticosteroids are excreted in breast milk; caution is advised. Monitor the infant for potential effects.

Storage

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

Formulations

• Tablets
• Injectable solutions
• Topical preparations

Mechanism of action

Methylsulphate functions as a methylating agent, transferring a methyl group to nucleophiles. This process involves the formation of a sulfonium ion, which is highly reactive and can readily react with nucleophilic sites on various substrates, leading to methylation reactions.

Pharmacodynamics

The pharmacodynamics of methylsulphate is primarily related to its role as a methylating agent in biochemical reactions. It can alter the structure and function of biological molecules, potentially affecting cellular processes and signaling pathways. However, detailed pharmacodynamic studies specific to therapeutic use are limited.

Pharmacokinetics

There is limited information on the pharmacokinetics of methylsulphate, given its typical use as a reagent in laboratory settings rather than a clinical drug. When used in chemical reactions, its reactivity and transformation into other compounds would dictate its pharmacokinetic profile, which could vary significantly based on the specific context of use.

Pregnancy

There is limited data on the use of methylsulphate in pregnancy. Consult relevant guidelines.

Breast-feeding

Data on the excretion of methylsulphate in human milk is not available. Caution is advised.

Storage

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

Indications

• Digestive aid
• Anti-inflammatory
• Potential psychoactive effects
• Antioxidant

Dosage

Children: Nutmeg is not commonly recommended for pediatric use due to the risk of toxicity and variability in individual responses. Consult pediatric guidelines and a healthcare professional for any medicinal use.

Adults: Dosage varies widely depending on the intended use, with culinary uses typically involving small amounts. For medicinal purposes, refer to specific guidelines and consult appropriate pharmacological references.

Mechanism of action

Nutmeg's active compounds, particularly myristicin and elemicin, exhibit anticholinergic properties by antagonizing acetylcholine receptors, which may lead to sedative and hallucinogenic effects at higher doses. Additionally, nutmeg may influence serotonin pathways, contributing to mood enhancement and altered consciousness. Its compounds also show antioxidant properties, which may support digestive health and reduce inflammation.

Pharmacodynamics

Nutmeg demonstrates a range of pharmacodynamic effects due to its complex mixture of phytochemicals. Its anticholinergic effects may lead to relaxation and mild euphoria, while its antioxidant properties help combat oxidative stress. The psychoactive effects are dose-dependent, with lower doses producing mild stimulation and higher doses potentially leading to hallucinations and adverse effects such as nausea and dizziness.

Pharmacokinetics

Nutmeg's active components are absorbed in the gastrointestinal tract and metabolized primarily in the liver. The half-life and specific metabolic pathways of nutmeg compounds vary; however, myristicin is known to be rapidly metabolized to various metabolites. The onset of effects may occur within a few hours after ingestion, with effects potentially lasting several hours, depending on the dose and individual metabolism.

Adverse effects

• Nausea
• Vomiting
• Dizziness
• Hallucinations
• Palpitations
• Drowsiness

Precautions

• Use with caution in individuals with liver disease
• Avoid in large amounts due to potential toxicity
• Monitor for adverse effects in sensitive individuals

Pregnancy

Nutmeg should be used with caution during pregnancy due to potential effects on the uterus and possible risk of miscarriage.

Breast-feeding

Limited information available, caution is advised due to potential adverse effects on infants.

Storage

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

Formulations

• Whole nutmeg
• Nutmeg powder
• Nutmeg oil

Indications

• Chronic venous insufficiency
• Osteoarthritis
• Hypertension
• Diabetes
• Cardiovascular health
• Antioxidant support

Dosage

Children: Refer to a healthcare professional or product guidelines for pediatric dosing, as safety and efficacy have not been well established in children.

Adults: Refer to the specific product guidelines, as dosages can vary based on the formulation and concentration of the extract.

Mechanism of action

The active compounds in pine bark extract, particularly proanthocyanidins, exert their effects through several mechanisms. They enhance nitric oxide production, which leads to vasodilation and improved blood flow. Additionally, they inhibit the oxidation of low-density lipoprotein (LDL) cholesterol, thus contributing to cardiovascular health. The antioxidant properties help reduce oxidative stress and inflammation by scavenging free radicals and modulating inflammatory pathways.

Pharmacodynamics

Pine bark extract displays a range of pharmacodynamic effects, including vasodilatory, anti-inflammatory, and antioxidant properties. These effects can lead to improved circulation, reduced symptoms of chronic venous insufficiency, and potential benefits in conditions associated with oxidative stress. The anti-inflammatory effects may also contribute to pain relief in osteoarthritis and other inflammatory conditions.

Pharmacokinetics

The pharmacokinetics of pine bark extract are influenced by its route of administration, typically oral. After ingestion, proanthocyanidins are absorbed in the gastrointestinal tract and distributed throughout the body. They undergo metabolic conversion in the liver, with a half-life that can vary based on individual metabolism and formulation. Elimination occurs primarily through urine, with metabolites detectable for several hours post-administration.

Adverse effects

• Allergic reactions
• Skin irritation
• Headache
• Gastrointestinal disturbances

Precautions

• Use with caution in individuals with known allergies to pine products.
• Monitor for allergic reactions in sensitive individuals.

Pregnancy

Pine products should be used with caution during pregnancy. Limited data is available regarding the safety of pine in pregnancy, consult a healthcare provider before use.

Breast-feeding

Caution is advised when using pine products while breastfeeding. Consult a healthcare provider for safety information.

Storage

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

Formulations

• Essential oil
• Extracts
• Topical ointments

Indications

• Pain relief
• Fever reduction
• Inflammatory conditions such as arthritis
• Prevention of cardiovascular events in certain populations

Dosage

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

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

Salicylate works by inhibiting the enzyme cyclooxygenase (COX), which is involved in the synthesis of prostaglandins. Prostaglandins are lipid compounds that mediate inflammation, pain, and fever. By decreasing the production of these compounds, salicylate effectively reduces inflammation and provides analgesic and antipyretic effects.

Pharmacodynamics

The pharmacodynamic effects of salicylate include analgesia, antipyresis, and anti-inflammatory action. It reduces the sensitivity of pain receptors and inhibits the generation of pain signals. The antipyretic effect is achieved through action on the hypothalamus, leading to peripheral vasodilation and sweating, thereby reducing body temperature. The drug also modulates the immune response, contributing to its anti-inflammatory properties.

Pharmacokinetics

Salicylate is rapidly absorbed from the gastrointestinal tract following oral administration. Peak plasma concentrations are typically reached within 1 to 2 hours. It is extensively metabolized in the liver, primarily through conjugation, and its metabolites are excreted in the urine. The elimination half-life of salicylate varies depending on the dose and the presence of other medications, averaging around 2 to 3 hours at low doses, but can be prolonged at higher doses due to saturation of metabolic pathways.

Contra-indications

• Hypersensitivity to salicylates
• Active peptic ulcer disease
• Severe hepatic impairment
• Severe renal impairment
• Bleeding disorders
• Children with viral infections (due to risk of Reye's syndrome)

Adverse effects

• Gastrointestinal irritation
• Nausea
• Vomiting
• Tinnitus
• Hearing loss
• Allergic reactions
• Rash
• Asthma exacerbation
• Gastric ulceration

Interactions

• Anticoagulants (increased bleeding risk)
• Methotrexate (increased toxicity)
• NSAIDs (increased gastrointestinal side effects)
• Diuretics (reduced efficacy)
• Alcohol (increased risk of gastrointestinal bleeding)

Precautions

• Use with caution in patients with a history of gastrointestinal disease
• Monitor renal function in long-term use
• Caution in patients with asthma or allergies
• Consider alternative therapy in children with viral infections

Pregnancy

Use with caution during pregnancy, particularly in the third trimester, as it may affect fetal development.

Breast-feeding

Salicylate is excreted in breast milk; caution is advised when administering to breastfeeding mothers.

Storage

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

Formulations

• Tablets
• Oral suspension
• Topical preparations
• Suppositories

Mechanism of action

Camphor is a naturally occurring compound that is used as a major active ingredient of balms and liniments supplied as topical analgesics. ... Capsaicin and menthol, two other topically applied agents widely used for similar purposes, are known to excite and desensitize sensory nerves by acting on two members of transient receptor potential (TRP) channel superfamily: heat-sensitive TRP vanilloid subtype 1 (TRPV1) and cold-sensitive TRP channel M8, respectively. Camphor has recently been shown to activate TRPV3, and here /investigators/ show that camphor also activates heterologously expressed TRPV1, requiring higher concentrations than capsaicin. Activation was enhanced by phospholipase C-coupled receptor stimulation mimicking inflamed conditions. Similar camphor-activated TRPV1-like currents were observed in isolated rat DRG neurons and were strongly potentiated after activation of protein kinase C with phorbol-12-myristate-13-acetate. Camphor activation of rat TRPV1 was mediated by distinct channel regions from capsaicin, as indicated by camphor activation in the presence of the competitive inhibitor capsazepine and in a capsaicin-insensitive point mutant. Camphor did not activate the capsaicin-insensitive chicken TRPV1. TRPV1 desensitization is believed to contribute to the analgesic actions of capsaicin. /The authors/ found that, although camphor activates TRPV1 less effectively, camphor application desensitized TRPV1 more rapidly and completely than capsaicin. Conversely, TRPV3 current sensitized after repeated camphor applications, which is inconsistent with the analgesic role of camphor. /Investigators/ also found that camphor inhibited several other related TRP channels, including ankyrin-repeat TRP 1 (TRPA1). The camphor-induced desensitization of TRPV1 and block of TRPA1 may underlie the analgesic effects of camphor.

Mechanism of action

The N-methyl-D-Aspartate (NMDA) receptor, a type of ionotropic receptor, is found on the dendrites of neurons and receives signals in the form of neurotransmitters. It is a major excitatory receptor in the brain. Normal physiological function requires that the activated receptor fluxes positive ions through the channel part of the receptor. PCP enters the ion channel from the outside of the neuron and binds, reversibly, to a site in the channel pore, blocking the flux of positive ions into the cell. PCP therefore inhibits depolarization of neurons and interferes with cognitive and other functions of the nervous system. Noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonists evoke a behavioral and neurobiological syndrome in experimental animals. We previously reported that phencyclidine (PCP), an NMDA receptor antagonist, increased locomotor activity in wildtype (WT) mice but not GluN2D subunit knockout mice. Thus, the aim of the present study was to determine whether the GluN2D subunit is involved in PCP-induced motor impairment. PCP or UBP141 (a GluN2D antagonist) induced potent motor impairment in WT mice but not GluN2D KO mice. By contrast, CIQ, a GluN2C/2D potentiator, induced severe motor impairment in GluN2D KO mice but not WT mice, suggesting that the GluN2D subunit plays an essential role in the effects of PCP and UBP141, and an appropriate balance between GluN2C and GluN2D subunits might be needed for appropriate motor performance. The level of the GluN2D subunit in the mature mouse brain is very low and restricted. GluN2D subunits exist in brainstem structures, the globus pallidus, thalamus, and subthalamic nucleus. We found that the expression of the c-fos gene increased the most among PCP-dependent differentially expressed genes between WT and GluN2D KO mice, and the number of Fos-positive cells increased after PCP administration in the basal ganglia motor circuit in WT mice but not GluN2D KO mice. These results suggest that the GluN2D subunit within the motor circuitry is a key subunit for PCP-induced motor impairment, which requires an intricate balance between GluN2C- and GluN2D-mediated excitatory outputs. Prepulse inhibition (PPI) is an example of sensorimotor gating and deficits in PPI have been demonstrated in schizophrenia patients. Phencyclidine (PCP) suppression of PPI in animals has been studied to elucidate the pathological elements of schizophrenia. However, the molecular mechanisms underlying PCP treatment or PPI in the brain are still poorly understood. In this study, quantitative phosphoproteomic analysis was performed on the prefrontal cortex from rats that were subjected to PPI after being systemically injected with PCP or saline. PCP downregulated phosphorylation events were significantly enriched in proteins associated with long-term potentiation (LTP). Importantly, this data set identifies functionally novel phosphorylation sites on known LTP-associated signaling molecules. In addition, mutagenesis of a significantly altered phosphorylation site on xCT (SLC7A11), the light chain of system xc-, the cystine/glutamate antiporter, suggests that PCP also regulates the activity of this protein. Finally, new insights were also derived on PPI signaling independent of PCP treatment. This is the first quantitative phosphorylation proteomic analysis providing new molecular insights into sensorimotor gating. Phencyclidine (PCP), a noncompetitive N-methyl-D-aspartate receptor antagonist, induces psychotomimetic effects in humans and animals. Administration of PCP to rodents is used as a preclinical model for schizophrenia; however, the molecular mechanisms underlying the symptoms remain largely unknown. Acute PCP treatment rapidly induces behavioral and cognitive deficits; therefore, post-translational regulation of protein activity is expected to play a role at early time points. We performed mass-spectrometry-driven quantitative analysis of rat frontal cortex 15, 30, or 240 min after the administ

Pharmacodynamics

Phencyclidine works primarily as an NMDA receptor antagonist, which blocks the activity of the NMDA Receptor.

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/