hTRPV1 (EC50 = 290 nM, HEK293 cells)[1]

In a dose- and time-dependent way, capsaicin (50–300 µM; 24-72 hours) significantly inhibited cell proliferation. It is estimated that the IC50 value is 150 µM[2]. Over a 24-72-hour period, capsaicin (50-300 µM) increases the expression of pro-apoptotic Bad/Bax and decreases anti-apoptotic Bcl-2 protein. It also activates caspase 3 and PARP (p85) levels in the cytosol[2]. Sub-G1 DNA concentration, nuclear condensation, and nuclear DNA fragmentation are all increased by capsaicin [2]. By downregulating the production of cyclin B1 and D1 regulatory factors as well as cyclin-dependent protein kinases cdk-1, cdk-2, and cdk-4, capsaicin prevents cell cycle progression in the G1/S phase in FaDu cells [2].

By altering the protein expression of the apoptotic regulatory factors p53, Bcl-2, Bax, and caspase-3, capsaicin prevents the growth of lung cancer [2].

Cloning and expression of human TRPV1[1]
A human embryonic kidney cell line stably expressing human TRPV1 (hTRPV1.HEK293 cells) was generated as described previously (Hayes et al., 2000). Cells were cultured on plastic tissue culture dishes in modified Eagles's medium with Earle's salts and supplemented with 10% fetal bovine serum, nonessential amino acids and 0.2 mm l-glutamine while being maintained under 5% CO2 at 37°C. For electrophysiological experiments, cells were plated at a 30,000 cells cm−2 density onto 19 mm glass coverslips coated with poly-l-lysine with experiments being performed 24–48 h thereafter.[1]

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Electrophysiological techniques[1]
Whole-cell patch-clamp experiments were performed according to standard methods, using an Axopatch 200B amplifier, as described previously (Hayes et al., 2000). Thick-walled borosilicate glass electrodes having 1.5–4 mΩ resistance were used to record currents following drug application using an automated three-barrelled solution switching device. The extracellular solution consisted of (mm): NaCl, 130; KCl, 5; BaCl2, 2; MgCl2, 1; glucose, 30; HEPES-NaOH, 25; pH 7.3 and electrodes were filled with intracellular solution as follows (mm): CsCl, 140; MgCl2, 4; EGTA, 10; HEPES-CsOH, 10; pH 7.3. Concentration–response curves were generated by comparing the peak response evoked by a test concentration of agonist to that evoked by a previous control current recorded in response to 1 μm capsaicin. Current–voltage relationships were established by measuring the net agonist-evoked current response during a voltage ramp (−70 to +70 mV). A baseline, obtained from the mean of two or three voltage-ramps in control solution prior to drug addition, was subtracted from the mean of three to five voltage-ramps at peak current in presence of drug (see Figure 2c). In these experiments, all data were normalised to the initial current obtained at the holding potential of −70 mV.

Cell Viability Assay[2]
Cell Types: Human Pharyngeal Squamous Carcinoma Cells (FaDu)
Tested Concentrations: 50 µM, 100 µM, 200 µM and 300 µM
Incubation Duration: 24 hrs (hours), 48 hrs (hours) and 72 hrs (hours)
Experimental Results: Cell growth shown.

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Apoptosis analysis[2]
Cell Types: FaDu Cell
Tested Concentrations: 50 µM, 100 µM and 200 µM
Incubation Duration: 12 hrs (hours)
Experimental Results: The activity of caspase 3 increased in a time-dependent manner.

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Western Blot Analysis[2]
Cell Types: FaDu Cell
Tested Concentrations: 200 µM
Incubation Duration: 24 hrs (hours)
Experimental Results: Activation of caspase 3 and PARP (p85) levels was observed.

Animal/Disease Models: Benzo(a)pyrene-induced Swiss albino mice (20-25 g; 8-10 weeks old) [3]
Doses: 10 mg/kg
Route of Administration: intraperitonealadministration; intraperitonealadministration. Once a week for 14 consecutive weeks
Experimental Results: Inhibits the development of lung cancer in mice.

Absorption, Distribution and Excretion
Oral Administration: After oral administration, capsaicin is absorbed from the stomach and whole intestine via an inactive process, with absorption rates varying from 50% to 90% depending on the animal. Peak plasma concentrations are reached within 1 hour after administration. After absorption from the stomach into the small intestine, capsaicin may undergo minor metabolism in the small intestinal epithelial cells. Although human oral pharmacokinetic information is limited, capsaicin is detectable in plasma within 10 minutes after ingestion of an equivalent dose of 26.6 mg of pure capsaicin, reaching a peak plasma concentration of 2.47 ± 0.13 ng/ml at 47.1 ± 2.0 minutes. Systemic Absorption: Following intravenous or subcutaneous injection in animals, drug concentrations in the brain and spinal cord are approximately 5 times higher than in the blood, and drug concentrations in the liver are approximately 3 times higher than in the blood. Topical Administration: Capsaicin is rapidly and adequately absorbed through human skin, but systemic absorption is unlikely after local or transdermal administration. A population analysis was conducted on patients using a topical patch containing 179 mg capsaicin, and plasma capsaicin concentrations were fitted using a one-compartment model of first-order absorption and linear elimination. The mean peak plasma concentration was 1.86 ng/mL, but the highest observed concentration in any patient was 17.8 ng/mL. It is presumed that capsaicin is primarily excreted by the kidneys in its original form and as a glucuronide. Small amounts of the original compound are excreted in feces and urine. In vivo animal studies showed that less than 10% of the administered dose was detected on the face after 48 hours. Prescription and over-the-counter medications for local analgesia, including creams, lotions, and patches, contain capsaicin (CAP) and dihydrocapsaicin (DHC). Currently, there are limited in vivo studies on the absorption, bioavailability, and distribution of CAP and DHC. We developed a sensitive and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determining the levels of CAP and DHC in rabbit plasma and tissues. Biological samples were prepared by liquid-liquid extraction using a hexane-dichloromethane-isopropanol mixture (100:50:5, v/v/v), followed by isocratic chromatography using an Extend C18 column. The mobile phase was acetonitrile-water-formic acid (70:30:0.1, v/v/v). For 100 μL of biological samples, the method was linear in the range of 0.125 to 50 ng/mL, with a limit of quantitation of 0.125 ng/mL. The total run time for analyzing each sample was 3.5 minutes. We used this validation method to investigate the pharmacokinetics and tissue distribution of topically applied capsaicin gel (CAP gel) in rabbits. Very small amounts of capsaicin and dihydrocapsaicin were absorbed into systemic circulation. The highest plasma concentration was 2.39 ng/mL, with a mean peak plasma concentration of 1.68 ng/mL 12 hours after CAP gel application. Drug concentrations were relatively high in the treated skin, but lower in other tissues. Therefore, topical application of capsaicin gel has strong local effects and weak systemic effects.

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Metabolism/Metabolites
The metabolic pathway of orally administered capsaicin is not yet clear, but it is expected to be primarily metabolized in the liver, with minimal metabolism in the intestinal lumen.In vitro studies have shown that capsaicin is rapidly metabolized in human liver microsomes and the S9 fragment, mainly producing three metabolites: 16-hydroxycapsaicin, 17-hydroxycapsaicin, and 16,17-hydroxycapsaicin, while vanillin is a minor metabolite. Studies speculate that cytochrome P450 (P450) enzymes may play a role in hepatic drug metabolism. In vitro studies have shown that the biotransformation of capsaicin in human skin is slow, with most capsaicin remaining unchanged. Capsaicin and dihydrocapsaicin are the main active ingredients in pepper spray, which is widely used for law enforcement and self-defense. Due to the irreversible health hazards of pepper spray, its use has been highly controversial. This study compared the metabolism and cytotoxicity of capsaicin and dihydrocapsaicin in vitro using human hepatocytes, porcine hepatocyte fractions, and the human lung cancer cell line (A549). Metabolites were screened and identified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). A novel dihydrocapsaicin aliphatic hydroxylated metabolite (m/z 322) was detected in hepatocyte fractions, but no structure corresponding to capsaicin was found. Conversely, a novel capsaicin phase I metabolite was identified, with a structure corresponding to aliphatic demethylation and dehydrogenation (m/z 294). Furthermore, two novel conjugates of capsaicin and dihydrocapsaicin were identified: glycine conjugates (m/z 363 and m/z 365) and diglutathione (GSH) conjugates (m/z 902 and m/z 904). A549 cell culture medium exposed to capsaicin contained capsaicin in ω-hydroxylated (m/z 322) and alkyl dehydrogenated (m/z 304) forms, as well as a glycine conjugate. For dihydrocapsaicin, an alkyl dehydrogenated form (m/z 306), a novel alkyl hydroxylated form, and a novel glycine conjugate were discovered. In A549 cells, dihydrocapsaicin induced cell vacuolation and reduced cell viability more effectively than capsaicin. Furthermore, both compounds induced p53 protein expression and G1 phase cell cycle arrest. The applicability of these metabolites as biomarkers for capsaicin exposure requires further investigation using other toxicity endpoints. ...Dehydrogenation of capsaicin is a novel metabolic pathway, producing unique cyclic, diene, and imide metabolites. 1-Aminobenzotriazole (1-ABT) inhibits the metabolism of capsaicin in microsomes. CYP1A1, 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4 catalyze the metabolism of capsaicin. Adding GSH (2 mM) to the microsomal incubation medium stimulates capsaicin metabolism and captures various active electrophilic intermediates, causing them to form adducts with GSH. /This study used recombinant P450 enzymes and liver and lung microsomes from multiple species, including humans./
This study aimed to characterize capsaicin glucuronidation using liver microsomes and determine the roles of various UDP-glucuronyltransferases (UGTs) in hepatic capsaicin glucuronidation. The glucuronidation rate was determined by incubating capsaicin with microsomes supplemented with uridine diphosphate glucuronide. Kinetic parameters were obtained through model fitting. Relative activity factors, expression-activity correlations, and activity correlations were determined to identify the major UGT enzymes involved in capsaicin metabolism. Capsaicin is efficiently glucuronidated in mixed human liver microsomes (pHLM). UGT1A1, 1A9, and 2B7 (as well as gastrointestinal enzymes UGT1A7 and 1A8) all exhibited relatively high activities. In a sample library containing liver microsomes from 14 individuals, capsaicin glucuronidation was significantly correlated with β-estradiol 3-O-glucuronidation (r=0.637; p=0.014) and UGT1A1 protein levels (r=0.616; p=0.019). Furthermore, capsaicin glucuronidation was significantly positively correlated with zidovudine glucuronidation (r=0.765; p<0.01) and UGT2B7 protein levels (r=0.721; p<0.01). In human liver microsomes (pHLM), UGT1A1, 1A9, and 2B7 contributed 30.3%, 6.0%, and 49.0% of total capsaicin glucuronidation, respectively. Moreover, the effect of liver microsomes on capsaicin glucuronidation showed significant species differences.

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Biological Half-Life
After oral administration of an equivalent dose of 26.6 mg of pure capsaicin, the half-life is approximately 24.9 ± 5.0 min. After topical application of a 3% capsaicin solution, the half-life of capsaicin is approximately 24 h.After using a topical patch containing 179 mg of capsaicin, the mean population elimination half-life is 1.64 hours.

Toxicity Summary
Identification and Uses: Capsaicin is a pure, deep red solid. It is used as a topical medicine and a tool in neurobiological research. Capsaicin and its derivatives are believed to have various health benefits, including anticancer, anti-inflammatory, anti-obesity, and analgesic activities. Topical capsaicin is used to treat postherpetic neuralgia, osteoarthritis, and diabetic neuropathy. However, the strong spiciness and potential neurotoxicity of these substances limit their use in food, nutritional supplements, and pharmaceuticals. Human Exposure and Toxicity: Capsaicin is a strong irritant; initial use causes severe pain. Prolonged use can lead to decreased sensitivity to painful stimuli and induce selective degeneration of certain primary sensory neurons. Pain caused by contact with capsaicin-containing peppers is one of the most common plant-related poisoning cases treated at poison control centers. It irritates the skin, causing a burning or stinging sensation; large ingestion in adults or small ingestion in children can cause nausea, vomiting, abdominal pain, and burning diarrhea. Contact with eyes can cause severe tearing, pain, conjunctivitis, and blepharospasm. The eye irritation caused by capsaicin has been used in pressurized dog repellent sprays containing capsaicin. One boy was accidentally sprayed with this spray; his eyes immediately stung, watered, and reddened, but returned to normal the next day. "Hunan hand" is a contact dermatitis caused by direct contact with capsaicin-containing chili peppers. In human lung and prostate cancer cells, capsaicin stimulates DNA double-strand breaks and the formation of micronuclei. Capsaicin has also been found to be an inducer of DNA hypermethylation in A549 cells. Animal experiments: Instillation of 50 μg/mL capsaicin into the eyes of rats caused significant pain and blepharospasm. Abnormally increased permeability of conjunctival and eyelid blood vessels to intravenously injected Evans blue dye was observed. Local anesthesia relieved pain but had no effect on vascular responses. Intravitreal injection of capsaicin into rabbit eyes caused pupillary constriction and disruption of the blood-aqueous barrier. The oral LD50 values for male and female mice were 118.8 mg/kg and 97.4 mg/kg, respectively, while those for male and female rats were 161.2 mg/kg and 148.1 mg/kg, respectively. The main toxic symptoms in mice included salivation, skin erythema, unsteady gait, slow breathing, and cyanosis. Some animals developed tremors, clonic seizures, dyspnea, and a lateral or prone position within 4 to 26 minutes after administration, subsequently dying. Mice recovered within 6 hours of survival, and rats recovered within 24 hours. The toxic symptoms in rats were almost identical to those in mice, but rats had a higher incidence of cyanosis, clonic or tonic seizures, dyspnea, and a lateral position, and their recovery time was later than in mice. Capsaicin caused developmental neurotoxicity in rats. Genetic toxicity tests confirmed that high-purity capsaicin did not exhibit genotoxicity in bacterial mutation and chromosomal aberration tests. Furthermore, no cytotoxicity or genotoxicity was observed in the rat bone marrow micronucleus test. Following a single injection of 7,12-dimethylbenzanthracene into female mice, repeated application of capsaicin to their shaved backs did not lead to a significant increase in papilloma formation, abnormal proliferation, or inflammatory skin lesions compared to the solvent control group. Topical application of capsaicin did not induce epidermal ornithine decarboxylase activity. When co-administered with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate, this compound reduced the incidence of skin cancer in mice. The burning and pain sensation induced by capsaicin originates from its chemical interaction with sensory neurons. As a vanillin compound, capsaicin binds to vanillin receptor 1 (VR1). Activation of VR1 allows cations to cross the cell membrane and enter the cell. The resulting neuronal depolarization stimulates the signaling to the brain. Capsaicin molecules, by binding to the VR1 receptor, produce a sensation similar to overheating or abrasion, explaining why the spiciness of capsaicin is described as a burning sensation. (L1246)

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Toxicity Data
LD50: 47200 ug/kg (oral, mouse) (T13)
LD50: 6500 ug/kg (intraperitoneal, mouse) (T13)
LD50: 9000 ug/kg (subcutaneous, mouse) (T13)
LD50: 400 ug/kg (intravenous, mouse) (T13)
LD50: 7800 ug/kg (intramuscular, mouse) (T13)
LD50: 1600 ug/kg (tracheal, mouse) (T13)

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Interactions
……After treatment of guinea pig tracheal smooth muscle preparations with capsaicin (0.3 uM; 30 min), tracheal contraction was significantly enhanced after maximal methacholine stimulation (capsaicin group: 1.147 ± 0.050 g, control group: 0.717 ± 0.050 g). 0.047 g). This effect completely disappeared after pretreatment with capsaicin receptor antagonists (2-[2-(4-chlorophenyl)ethyl-amino-thiocarbonyl]-7,8-dihydroxy-2,3,4,5-tetrahydro-1H-2-benzozazepine; a vanillin receptor antagonist) and YM38336 (a dual receptor antagonist for tachykinin NK1 and tachykinin NK2). Treatment of HL-60 cells with 5-30 μg/mL capsaicin for 72 hours inhibited cell proliferation and slightly increased cell differentiation. A synergistic induction of HL-60 cell differentiation was observed when capsaicin was used in combination with 5 nM 1,25-(OH)₂D₃ or 50 nM all-trans retinoic acid. Flow cytometry analysis showed that the combination of 1,25-(OH)₂D₃ and capsaicin primarily stimulated cell differentiation into monocytes, while the combination of all-trans retinoic acid and capsaicin primarily stimulated cell differentiation into granulocytes. Capsaicin enhanced the activity of protein kinase C in HL-60 cells treated with 1,25-(OH)₂D₃ and all-trans retinoic acid. Furthermore, protein kinase C inhibitors [bisindolylmaleimide (GF-109203X), chelerythrine, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7)] and extracellular signal-regulated kinase inhibitors [2-(2'-amino-3'-methoxyphenyl)-oxonaphth-4-one (PD-098059)] significantly inhibited HL-60 cell differentiation induced by capsaicin combined with 1,25-(OH)₂D₃ or all-trans retinoic acid.
...Capsaicin and nonanamide significantly enhanced the transport of indomethacin in the skin of nude mice. ...Histological examination combined with visual scoring indicated that capsaicin and nonanamide were safe for skin structures. The combined use of ultrasound and the enhancer significantly improved the skin penetration of indomethacin compared to the use of ultrasound or the enhancer alone.
Treatment of neonatal rats with capsaicin, a transient receptor potential vanillic acid receptor 1 (TRPV1) channel agonist, resulted in the lifelong loss of sensory neurons expressing the TRPV1 channel. Previous studies have shown that rats treated with capsaicin on day 2 after birth exhibited hyperactivity in new environments at 5-7 weeks of age, and brain changes similar to those observed in patients with schizophrenia. This study aimed to investigate the brain and behavioral responses of adult rats treated with capsaicin during neonatal period. The study found that the brain changes observed in neonatal rats treated with capsaicin at 5-7 weeks of age persisted into adulthood (12 weeks of age), but were reduced in older rats (16-18 weeks of age). These rats exhibited enhanced pre-pulse inhibition (PPI) of the vocal startle reflex at 8 and 12 weeks of age, rather than the PPI deficiency commonly seen in animal models of schizophrenia. Erythematous responses to nicotinic acid and methyl nicotinate were also reduced in schizophrenic patients, which is thought to be mediated by prostaglandin D2 (PGD2). Erythematous responses were accompanied by skin plasma exudation. The study found that capsaicin-treated rats exhibited reduced skin plasma exudation responses to methyl nicotinate and PGD2. In summary, the several neuroanatomical changes observed in capsaicin-treated rats, along with the reduction in skin plasma exudation responses, suggest that the role of the TRPV1 channel in schizophrenia warrants further investigation.
For more complete data on capsaicin interactions (21 items in total), please visit the HSDB records page.

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Non-human toxicity values
Oral LD50 in mice >2500 mg/kg
Intraperitoneal LD50 in rats 9500 ug/kg
Oral LD50 in mice 47200 ug/kg
Intraperitoneal LD50 in mice 6500 ug/kg
For more complete (13) non-human toxicity values of capsaicin, please visit the HSDB record page.

[1]. McNamara FN, et al. Effects of piperine, the pungent component of black pepper, at the human vanilloid receptor (TRPV1). Br J Pharmacol. 2005 Mar;144(6):781-90.
[2]. Shin YH, et al. The Effect of Capsaicin on Salivary Gland Dysfunction. Molecules. 2016 Jun 25;21(7).
[3]. Anandakumar P, et al. Capsaicin provokes apoptosis and restricts benzo(a)pyrene induced lung tumorigenesis in Swiss albino mice. Int Immunopharmacol. 2013 Jun 6;17(2):254-259.

Therapeutic Uses
Capsaicin appears to be effective for osteoarthritis (OA) pain, but its efficacy remains uncertain regarding dose-response relationships, consistency across different joints, and whether it changes over time. We searched PubMed, EMBASE, and ISI Web of Knowledge databases for randomized controlled trials (RCTs) of topical capsaicin for OA. Using RevMan software, we assessed the effects of capsaicin on pain scores, overall patient feedback on treatment effectiveness, and burning sensation at the application site using standardized mean difference (SMD). A total of 5 double-blind RCTs and 1 case-crossover trial were retrieved. Capsaicin concentrations ranged from 0.025% to 0.075%, and trial durations ranged from 4 to 12 weeks. Trials evaluated OA in the knee (n=3), hand (n=1), and mixed joints (n=2). The efficacy of capsaicin treatment in changing VAS pain scores (compared to placebo) was moderate, with an efficacy of 0.44 (95% CI: 0.25–0.62) after 4 weeks of treatment. There was no heterogeneity among studies, indicating no differences between studies, including the effect of OA site or treatment concentration. Two studies reported treatment durations exceeding 4 weeks with conflicting results. One study reported an effect size of -9 mm after 12 weeks, with the inter-group difference reaching its maximum at week 4. The other study reported that the inter-group difference increased over time, up to week 20. Capsaicin has been reported to be safe and well-tolerated, with no systemic toxicity. Mild application site burning occurred in 35% to 100% of patients treated with capsaicin, with a hazard ratio of 4.22 (95% CI: 3.25–5.48, n=5 trials); the incidence peaked at week 1 and subsequently decreased over time. For patients with at least moderate pain and a clinically or radiologically confirmed diagnosis of osteoarthritis, topical capsaicin applied four times daily effectively reduced pain intensity for up to 20 weeks, regardless of application site and dosage, and was well-tolerated. Cough sensitivity is common in respiratory diseases. This study aimed to determine the association between capsaicin cough sensitivity and clinical parameters in clinically stable adult patients with bronchiectasis. We recruited 135 consecutively attending adult patients with bronchiectasis and 22 healthy subjects. All subjects underwent history taking, sputum culture, pulmonary function tests, high-resolution computed tomography (HRCT) of the chest, Leicester Cough Questionnaire score, Bronchiectasis Severity Index (BSI) assessment, and capsaicin inhalation challenge test. Cough sensitivity was measured by the capsaicin concentration required to elicit at least two coughs (C2) and five coughs (C5). Although there was significant overlap between healthy subjects and bronchiectasis patients, the latter had significantly lower C2 and C5 levels than healthy subjects (all p < 0.01). Lower C5 levels were associated with longer duration of bronchiectasis symptoms, worse HRCT scores, higher 24-hour sputum volume, higher BSI and purulent sputum scores, and positive sputum cultures for Pseudomonas aeruginosa. Determinants associated with increased capsaicin cough sensitivity (defined as C5 ≤ 62.5 μmol/L) included: female sex (OR: 3.25, 95% CI: 1.35–7.83, p < 0.01), total HRCT score between 7 and 12 (OR: 2.57, 95% CI: 1.07–6.173, p = 0.04), BSI score between 5 and 8 (OR: 4.05, 95% CI: 1.48–11.06, p < 0.01), and ≥ 9 (OR: 4.38, 95% CI: 1.48–12.93, p < 0.01). Capsaicin cough susceptibility is elevated in some patients with bronchiectasis and is correlated with disease severity. Sex and disease severity (rather than purulent sputum) are independent determinants of increased capsaicin cough susceptibility. Current diagnostic methods for cough susceptibility may have limitations due to overlap with healthy subjects, but may provide objective indicators for cough assessment in future clinical trials. Chronic unexplained cough induced by environmental irritants is characterized by increased cough reflex susceptibility, which can be confirmed by inhaled capsaicin. Topical application of capsaicin can improve non-allergic rhinitis and intestinal hypersensitivity, and reduce neuropathic pain. We investigated whether oral administration of natural capsaicin (capsicum) could reduce cough reflex susceptibility and improve unexplained cough. This study included 24 patients with irritant-induced unexplained chronic cough and 15 healthy controls. Subjects received either pure capsaicin capsules for 4 weeks or placebo capsules for 4 weeks. The study was crossover, randomized, and double-blind. Cough susceptibility was assessed during the study using a standardized capsaicin inhalation cough test, which determined the capsaicin concentrations required to achieve two coughs (C2) and five coughs (C5). Participants also completed questionnaires about cough and cough-related symptoms. Three patients withdrew before the end of the study, one during the active treatment period and two during the placebo period. Following capsaicin treatment, the C2 threshold was higher in both the patient group (p<0.020) and the control group (p<0.0061) than in the placebo period (improvement). In the patient group, the concentrations required to reach C2 (p<0.0004) and C5 (p<0.0009) after active treatment were higher than the baseline cough threshold. Four weeks after active treatment, cough symptom scores improved compared to baseline (p<0.0030). Oral capsaicin powder reduced capsaicin cough sensitivity and cough symptoms. The results suggest desensitization to the transient receptor potential vanillic acid receptor 1 (TRPV1) for cough sensitivity. Qutenza is a high-dose capsaicin patch used to relieve neuropathic pain caused by postherpetic neuralgia (PHN) and HIV-associated neuropathy (HIV-AN). Clinical studies have shown that some patients respond significantly to capsaicin patches. Our goal was to identify the baseline characteristics of patients who would most benefit from capsaicin patch treatment. We performed a meta-analysis of six completed Qutenza randomized controlled trials, summarizing individual patient data. Sustained remission was defined as a mean reduction in pain intensity of more than 50% from baseline to weeks 2–12, and complete remission was defined as a mean pain intensity score of 1 from weeks 2–12. We used logistic regression analysis to identify predictors of remission and complete remission, as well as the subgroups of patients who responded best to capsaicin patches. A baseline pain intensity score (BPIS) of 4 was a predictor of sustained and complete remission in patients with postherpetic neuralgia (PHN) and HIV-associated neuralgia (HIV-AN); the absence of hyperalgesia, presence of hypoalgesia, and a McGill Pain Questionnaire (MPQ) sensory score <22 were predictors of sustained remission in PHN patients; female sex was a predictor of sustained and complete remission in HIV-AN patients. Therefore, the characteristics associated with the highest response rate to capsaicin patch treatment are: BPIS=4, MPQ sensory score=22, absence of hyperalgesia, and presence of hypoalgesia for PHN patients; and for HIV-AN patients, female sex and BPIS=4. Patients with these characteristics have a significantly higher response rate to capsaicin patches than other patients. For more complete data on the therapeutic uses of capsaicin (21 types), please visit the HSDB record page.

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Drug Warnings
A mild to moderate burning sensation may occur after use. Some patients may experience a more severe burning sensation and need to discontinue treatment.
Capsaicin must be prevented from entering the eyes, open wounds, or mucous membranes.
…Capsaicin is for external use only. Do not apply to wounds, damaged or irritated skin. Do not wrap tightly. Capsaicin should not come into contact with mucous membranes, eyes, or contact lenses. If this occurs, immediately rinse the affected area thoroughly with water. If the condition worsens or does not improve with regular use, discontinue use of this product and consult a healthcare professional. If blisters or a severe burning sensation persists, do not heat the treated area immediately before or after application, as this may worsen the burning sensation. /Over-the-counter Capsaicin/
Do not apply prescription capsaicin to the face or scalp to avoid contact with eyes or mucous membranes.
For more complete data on drug warnings for capsaicin (14 in total), please visit the HSDB record page.

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Pharmacodynamics
Capsaicin is a TRPV1 receptor agonist. TRPV1 is a transmembrane receptor-ion channel complex that can be activated by temperatures above 43°C, pH values below 6, and endogenous lipids. When these factors are activated together, the channel can open transiently and induce depolarization due to the influx of calcium and sodium ions. Since TRPV1 is primarily expressed in A-δ and C fibers, its depolarization generates action potentials and transmits impulses to the brain and spinal cord. These impulses cause capsaicin to produce reactions such as warmth, tingling, itching, burning, or a burning sensation. Compared to environmental agonists, capsaicin also causes more persistent activation of these receptors, leading to a loss of response to many sensory stimuli, a phenomenon known as "loss of function." Capsaicin also induces various enzymatic, cytoskeletal, and osmotic changes, as well as disturbances in mitochondrial respiration, thereby impairing nociceptor function over a prolonged period.

C18H27NO3

293.4012

305.199

C, 70.79; H, 8.91; N, 4.59; O, 15.72

404-86-4

Capsaicinoid;404-86-4;(E/Z)-Capsaicin-d3;1185237-43-7;(Z)-Capsaicin;25775-90-0;Capsaicin-d3;1217899-52-9

1548943

Pure dark red solid
Monoclinic rectangular plates or scales from petroleum ether
Monoclinic, rectangular plates, crystals and scales

1.0±0.1 g/cm3

469.7±55.0 °C at 760 mmHg

62-65 °C(lit.)

237.9±31.5 °C

0.0±1.2 mmHg at 25°C

1.508

4.27

2

3

9

22

341

0

O=C(C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])N([H])C([H])([H])C1C([H])=C([H])C(=C(C=1[H])OC([H])([H])[H])O[H]

YKPUWZUDDOIDPM-SOFGYWHQSA-N

InChI=1S/C18H27NO3/c1-14(2)8-6-4-5-7-9-18(21)19-13-15-10-11-16(20)17(12-15)22-3/h6,8,10-12,14,20H,4-5,7,9,13H2,1-3H3,(H,19,21)/b8-6+

8-Methyl-N-vanillyl-(trans)-6-nonenamide

(E)-Capsaicin Capsicine Capsicin PS C (E)Capsaicin; Zostrix; CAPSAICINE; Qutenza; Styptysat; Axsain;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~327.43 mM)

Solubility in Formulation 1: ≥ 20 mg/mL (65.49 mM) (saturation unknown) in 10% EtOH + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 200.0 mg/mL clear EtOH stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (8.19 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (8.19 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 4: ≥ 2.5 mg/mL (8.19 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)