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**: Following oral administration, capsaicin may be absorbed by a nonactive process from the stomach and whole intestine with an extent of absorption ranging between 50 and 90%, depending on the animal. The peak blood concentration can be reached within 1 hour following administration. Capsaicin may undergo minor metabolism in the small intestine epithelial cells post-absorption from the stomach into the small intestines. While oral pharmacokinetics information in humans is limited, ingestion of equipotent dose of 26.6 mg of pure capsaicin, capsaicin was detected in the plasma after 10 minutes and the peak plasma concentration of 2.47 ± 0.13 ng/ml was reached at 47.1 ± 2.0 minutes. **Systemic**: Following intravenous or subcutaneous administration in animals, the concentrations in the brain and spinal cord were approximately 5-fold higher than that in blood and the concentration in the liver was approximately 3-fold higher than that in blood. **Topical**: Topical capsaicin in humans is rapidly and well absorbed through the skin, however systemic absorption following topical or transdermal administration is unlikely. For patients receiving the topical patch containing 179 mg of capsaicin, a population analysis was performed and plasma concentrations of capsaicin were fitted using a one-compartment model with first-order absorption and linear elimination. The mean peak plasma concentration was 1.86 ng/mL but the maximum value observed in any patient was 17.8 ng/mL.
It is proposed that capsaicin mainly undergoes renal excretion, as both the unchanged and glucuronide form. A small fraction of unchanged compound is excreted in the feces and urine. _In vivo_ animal studies demonstrates that less than 10 % of an administered dose was found in faces after 48 h.
Prescription and nonprescription products for topical management of pain, including cream, lotion and patch forms, contain capsaicin (CAP) and dihydrocapsaicin (DHC). There are few in vivo studies on absorption, bioavailability, and disposition of CAP and DHC. We established a sensitive and rapid LC-MS/MS assay to determine CAP and DHC levels in rabbit plasma and tissue. Bio-samples prepared by liquid-liquid extraction using n-hexane-dichloromethane-isopropanol (100: 50: 5, v/v/v) mixture were separated by isocratic chromatography with an Extend C18 column. The mobile phase was acetonitrile-water-formic acid (70: 30: 0.1, v/v/v). The method was linear from 0.125 to 50 ng/mL for a 100 uL bio-sample, and the lower quantification limit was 0.125 ng/mL. Total run time to analyze each sample was 3.5 min. We used this validated method to study pharmacokinetics and tissue distribution of CAP gel administered topically to rabbits. A very small amount of CAP and DHC was absorbed into the systemic circulation. The highest plasma concentration was 2.39 ng/mL, and the mean peak plasma concentration value after 12 h of CAP gel application was 1.68 ng/mL. Drug concentration in treated skin was relatively high, with low concentration in other tissues. Thus, topical CAP gel had strong local effects and weaker systemic effects.

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Metabolism / Metabolites
Capsaicin metabolism after oral administration is unclear, however it is expected to undergo metabolism in the liver with minimal metabolism in the gut lumen. _In vitro_ studies with human hepatic microsomes and S9 fragments indicate that capsaicin is rapidly metabolized, producing three major metabolites, 16-hydroxycapsaicin, 17-hydroxycapsaicin, and 16,17-hydroxycapsaicin, whereas vanillin was a minor metabolite. It is proposed that cytochrome P450 (P450) enzymes may play some role in hepatic drug metabolism. _In vitro_ studies of capsaicin in human skin suggest slow biotransformation with most capsaicin remaining unchanged.
Capsaicin and dihydrocapsaicin are the major active components in pepper spray products, which are widely used for law enforcement and self-protection. The use of pepper sprays, due to their irreversible and other health effects has been under a strong debate. In this study, we compared metabolism and cytotoxicity of capsaicin and dihydrocapsaicin using human and pig liver cell fractions and human lung carcinoma cell line (A549) in vitro. Metabolites were screened and identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Using liver cell fractions, a novel aliphatic hydroxylated metabolite (m/z 322) was detected to dihydrocapsaicin but no structure was found corresponding to capsaicin. Instead, a novel phase I metabolite of capsaicin, corresponding to the structure of aliphatic demethylation and dehydrogenation (m/z 294) was identified. In addition, two novel conjugates, glycine conjugates (m/z 363 and m/z 365) and bi-glutathione (GSH) conjugates (m/z 902 and m/z 904), were identified for both capsaicin and dihydrocapsaicin. The medium of the exposed A549 cells contained omega-hydroxylated (m/z 322) and alkyl dehydrogenated (m/z 304) forms, as well as a glycine conjugate of capsaicin. As to dihydrocapsaicin, an alkyl dehydrogenated (m/z 306) form, a novel alkyl hydroxylated form, and a novel glycine conjugate were found. In A549 cells, dihydrocapsaicin evoked vacuolization and decreased cell viability more efficiently than capsaicin. Furthermore, both compounds induced p53 protein and G1 phase cell cycle arrest. Usefulness of the found metabolites as biomarkers for capsaicinoid exposures will need further investigations with additional toxicity endpoints.
... Dehydrogenation of capsaicin was a novel metabolic pathway and produced unique macrocyclic, diene, and imide metabolites. Metabolism of capsaicin by microsomes was inhibited by 1-aminobenzotriazole (1-ABT). Metabolism was catalyzed by CYP1A1, 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4. Addition of GSH (2 mM) to microsomal incubations stimulated the metabolism of capsaicin and trapped several reactive electrophilic intermediates as their GSH adducts. /Study conducted with recombinant P450 enzymes and hepatic and lung microsomes from various species, including humans/
The objectives of this study are to characterize capsaicin glucuronidation using liver microsomes and to determine the contribution of individual UDP-glucuronosyltransferase (UGT) enzymes to hepatic glucuronidation of capsaicin. The rates of glucuronidation were determined by incubating capsaicin with uridine diphosphoglucuronic acid-supplemented microsomes. Kinetic parameters were derived by model fitting. Determination of the relative activity factors, expression-activity correlation and activity correlation analysis were performed to identify the main UGT enzymes contributing to capsaicin metabolism. Capsaicin was efficiently glucuronidated in pooled human liver microsomes (pHLM). UGT1A1, 1A9 and 2B7 (as well as the gastrointestinal enzymes UGT1A7 and 1A8) showed considerable activities. Capsaicin glucuronidation was significantly correlated with 3-O-glucuronidation of beta-estradiol (r=0.637; p=0.014) and with UGT1A1 protein levels (r=0.616; p=0.019) in a bank of individual HLMs (n=14). Also, capsaicin glucuronidation was strongly correlated with zidovudine glucuronidation (r=0.765; p<0.01) and with UGT2B7 protein levels (r=0.721; p<0.01). UGT1A1, 1A9 and 2B7 contributed 30.3, 6.0 and 49.0% of total glucuronidation of capsaicin in pHLM, respectively. Further, glucuronidation of capsaicin by liver microsomes showed marked species difference.

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Biological Half-Life
Following oral ingestion of equipotent dose of 26.6 mg of pure capsaicin, the half life was approximately 24.9 ± 5.0 min. Following topical application of 3% solution of capsaicin, the half-life of capsaicin was approximately 24 h. The mean population elimination half-life was 1.64 h following application of a topical patch containing 179 mg of capsaicin.

Toxicity Summary
IDENTIFICATION AND USE: Capsaicin is a pure dark red solid. It is used as a topical medication and a tool in neurobiological research. A number of health benefits have been ascribed to capsaicin and its derivatives, including anticancer activity, anti-inflammatory activity, anti-obesity activity, and analgesia. Topical capsaicin is used in the treatment of postherpetic neuralgia, osteoarthritis, and painful diabetic neuropathy. However, the strong pungency of these substances and potential for neurotoxicity limit their use in food, nutritional supplements, and pharmaceuticals. HUMAN EXPOSURE AND TOXICITY: Capsaicin is a powerful irritant; initial administration causes intense pain. Prolonged treatment causes insensitivity to painful stimuli and induces selective degeneration of certain primary sensory neurons. Painful exposures to capsaicin-containing peppers are among the most common plant-related exposures presented to poison centers. They cause burning or stinging pain to the skin, and if ingested in large amounts by adults or small amounts by children, can produce nausea, vomiting, abdominal pain, and burning diarrhea. Eye exposure produce intense tearing, pain, conjunctivitis, and blepharospasm. The irritating effect on the eyes has been utilized in pressurized dog repellent sprays which incorporate capsaicin. One boy accidentally had his eyes sprayed with this material. His eyes immediately smarted, teared, and became red, but were normal by the next day. "Hunan hand" is a contact dermatitis resulting from the direct handling of chili peppers containing capsaicin. In human lung and prostate cancer cells capsaicin stimulated both DNA double strand breaks and micronuclei production. Capsaicin was also found to be a DNA hypermethylating agent in A549 cells. ANIMAL STUDIES: Fifty ug/mL applied on the eyes of rats has caused obvious pain and blepharospasm. The blood vessels of the conjunctivae and lids became abnormally permeable to Evans blue dye injected intravenously. Application of local anesthetic prevented pain, but did not alter the vascular reaction. Intravitreal injection of capsaicin in rabbits causes miosis and breakdown of the blood-aqueous barrier. Oral LD50 values were 118.8 mg/kg for male and 97.4 mg/kg for female mice, and 161.2 mg/kg for male and 148.1 mg/kg for female rats. Major toxic symptoms in mice were salivation, erythema of skin, staggering gait, bradypnea, and cyanosis. Some animals showed tremor, clonic convulsion, dyspnea and lateral or prone position and then died 4 to 26 min after dosing. Survivors recovered within 6 hr in mice and 24 hr in rats. Toxic symptoms of rats were almost the same as mice, but rats showing higher incidence of cyanosis, clonic or tonic convulsion, dyspnea and lateral position, and the recovery was later than mice. Capsaicin caused developmental neurotoxicity in rats. The results of genotoxicity testing confirm the absence of genotoxic activity of high-purity capsaicin in the bacterial mutation and chromosome aberration tests. In addition, no evidence of cytotoxicity or genotoxicity was seen in the rat bone marrow micronucleus test. Repeated applications of capsaicin onto the shaven backs of female mice following a single-initiation dose of 7,12-dimethylbenz(a)anthracene did not cause any significant increase in papilloma formation and abnormal hyperplastic or inflammatory skin lesions, compared with the solvent control. Topical application of capsaicin did not induce the epidermal ornithine decarboxylase activity. The compound ameliorated the mouse skin carcinogenesis when given simultaneously with the tumor promoter, 12-o-tetradecanoylphorbol-13-acetate.
The burning and painful sensations associated with capsaicin result from its chemical interaction with sensory neurons. Capsaicin, as a member of the vanilloid family, binds to the vanilloid receptor 1 (VR1). VR1 permits cations to pass through the cell membrane and into the cell when activated. The resulting depolarization of the neuron stimulates it to signal the brain. By binding to the VR1 receptor, the capsaicin molecule produces the same sensation that excessive heat or abrasive damage would cause, 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 (Intratracheal, Mouse) (T13)

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Interactions
... after capsaicin (0.3 uM; 30 min) treatment of guinea pig tracheal smooth muscle preparations, the maximal contraction of the trachea after methacholine stimulation was strongly increased (capsaicin: 1.147 +/- 0.050 g vs. control: 0.717 +/- 0.047 g). This effect was completely nullified after pretreatment with capsazepine (2-[2-(4-chlorophenyl)ethyl-amino-thiocarbonyl]-7,8-dihydroxy-2,3, 4,5-tetrahydro-1H-2benzazepine; a vanilloid receptor antagonist) and YM38336 (a dual tachykinin NK1 and tachykinin NK2 receptor antagonist).
... Treatment of HL-60 cells with 5-30 ug/mL capsaicin for 72 hr inhibited cell proliferation and induced a small increase in cell differentiation. Synergistic induction of HL-60 cell differentiation was observed when capsaicin was combined with either 5 nM 1,25-(OH)2D3 or 50 nM all-trans retinoic acid. Flow cytometric analysis indicated that combinations of 1,25-(OH)2D3 and capsaicin stimulated differentiation predominantly to monocytes whereas combinations of all-trans retinoic acid and capsaicin stimulated differentiation predominantly to granulocytes. Capsaicin enhanced protein kinase C activity in 1,25-(OH)2D3- and all-trans retinoic acid-treated HL-60 cells. In addition, inhibitors for protein kinase C [bisindolylmaleimide (GF-109203X), chelerythrine, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7)] and an inhibitor for extracellular signal-regulated kinase [2-(2'-amino-3'-methoxyphenyl)-oxanaphthalen-4-one (PD-098059)] significantly inhibited HL-60 cell differentiation induced by capsaicin in combination with either 1,25-(OH)2D3 or all-trans retinoic acid.
... Capsaicin and nonivamide significantly enhanced the flux of indomethacin across nude mouse skin. ... Histological examination coupled with visual scores indicated the safety of capsaicin and nonivamide on skin structure. Simultaneous application of ultrasound and enhancers significantly increased skin permeation of indomethacin compared with either ultrasound or enhancers alone.
Treatment of neonatal rats with the transient receptor potential vanilloid 1 (TRPV1) channel agonist, capsaicin, produces life-long loss of sensory neurons expressing TRPV1 channels. Previously it was shown that rats treated on day 2 of life with capsaicin had behavioral hyperactivity in a novel environment at 5-7 weeks of age and brain changes reminiscent of those found in subjects with schizophrenia. The objective of the present study was to investigate brain and behavioral responses of adult rats treated as neonates with capsaicin. It was found that the brain changes found at 5-7 weeks in rats treated as neonates with capsaicin persisted into adulthood (12 weeks) but were less in older rats (16-18 weeks). Increased prepulse inhibition (PPI) of acoustic startle was found in these rats at 8 and 12 weeks of age rather than the deficit commonly found in animal models of schizophrenia. Subjects with schizophrenia also have reduced flare responses to niacin and methylnicotinate proposed to be mediated by prostaglandin D2 (PGD2). Flare responses are accompanied by cutaneous plasma extravasation. It was found that the cutaneous plasma extravasation responses to methylnicotinate and PGD2 were reduced in capsaicin-treated rats. In conclusion, several neuroanatomical changes observed in capsaicin-treated rats, as well as the reduced cutaneous plasma extravasation responses, indicate that the role of TRPV1 channels in schizophrenia is worthy of investigation.
For more Interactions (Complete) data for CAPSAICIN (21 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Mouse oral >2500 mg/kg
LD50 Rat ip 9500 ug/kg
LD50 Mouse oral 47200 ug/kg
LD50 Mouse ip 6500 ug/kg
For more Non-Human Toxicity Values (Complete) data for CAPSAICIN (13 total), 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 it is uncertain whether the effect has a dose response, is consistent across joints, or changes over time. Randomized controlled trials of topical capsaicin use in OA were identified from PubMed, EMBASE, and ISI Web of Knowledge. Effect on pain scores, patient global evaluation of treatment effectiveness and application site burning were assessed by standardised mean differences (SMD), using RevMan. Five double-blind randomized controlled trials and one case-crossover trial of topical capsaicin use were identified. Formulations ranged from 0.025 to 0.075%, and trial durations from 4 to 12 weeks. Trials assessed OA of the knee (n=3), hand (n=1), and a mix of joints (n=2). Capsaicin treatment efficacy (vs. placebo) for change in VAS pain score was moderate, at 0.44 (95% CI: 0.25-0.62) over 4 weeks of treatment. There was no heterogeneity between studies, indicating no between-study differences, including effect of OA site or treatment concentration. Two studies reported treatment beyond 4 weeks, with divergent results. One study reported an effect size of -9 mm after 12 weeks, and maximal between-group differences at 4 weeks. A second study reported that between-group differences increased over time, up to 20 weeks. Capsaicin was reported as being safe and well-tolerated, with no systemic toxicity. Mild application site burning affected 35-100% of capsaicin-treated patients with a risk ratio of 4.22 (95% CI: 3.25-5.48, n=5 trials); incidence peaked in week 1, with incidence rates declining over time. Topical capsaicin treatment four times daily is moderately effective in reducing pain intensity up to 20 weeks regardless of site of application and dose in patients with at least moderate pain and clinical or radiologically defined OA, and is well tolerated.
Cough hypersensitivity has been common among respiratory diseases. /The study objective was/ to determine associations of capsaicin cough sensitivity and clinical parameters in adults with clinically stable bronchiectasis. We recruited 135 consecutive adult bronchiectasis patients and 22 healthy subjects. History inquiry, sputum culture, spirometry, chest high-resolution computed tomography (HRCT), Leicester Cough Questionnaire scoring, Bronchiectasis Severity Index (BSI) assessment and capsaicin inhalation challenge were performed. Cough sensitivity was measured as the capsaicin concentration eliciting at least 2 (C2) and 5 coughs (C5). Despite significant overlap between healthy subjects and bronchiectasis patients, both C2 and C5 were significantly lower in the latter group (all p<0.01). Lower levels of C5 were associated with a longer duration of bronchiectasis symptoms, worse HRCT score, higher 24-hour sputum volume, BSI and sputum purulence score, and sputum culture positive for P. aeruginosa. Determinants associated with increased capsaicin cough sensitivity, defined as C5 being 62.5 umol/L or less, encompassed female gender (OR: 3.25, 95%CI: 1.35-7.83, p<0.01), HRCT total score between 7-12 (OR: 2.57, 95%CI: 1.07-6.173, p=0.04), BSI between 5-8 (OR: 4.05, 95%CI: 1.48-11.06, p<0.01) and 9 or greater (OR: 4.38, 95%CI: 1.48-12.93, p<0.01). Capsaicin cough sensitivity is heightened in a subgroup of bronchiectasis patients and associated with the disease severity. Gender and disease severity, but not sputum purulence, are independent determinants of heightened capsaicin cough sensitivity. Current testing for cough sensitivity diagnosis may be limited because of overlap with healthy subjects but might provide an objective index for assessment of cough in future clinical trials.
Chronic unexplained cough triggered by environmental irritants is characterized by increased cough reflex sensitivity, which can be demonstrated by means of inhaled capsaicin. Topical capsaicin can be used to improve non-allergic rhinitis and intestinal hypersensitivity and to reduce neuropathic pain. We established whether an oral intake of natural capsaicin (chilli) could desensitize the cough reflex and improve unexplained coughing. Twenty-four patients with irritant-induced, unexplained chronic cough and 15 controls were included in the study. For 4 weeks, the participants took capsules with pure capsaicin, and for 4 weeks, they took placebo capsules. The protocol was crossover, randomized, and double blind. Cough sensitivity during the study was evaluated by a standardized capsaicin inhalation cough test that assessed the capsaicin concentration required to reach two coughs (C2) and five coughs (C5). Participants were also administered questionnaires on cough and cough-related symptoms. Three patients withdrew before the study end, one during the active treatment period and two during the placebo period. After treatment with capsaicin, the thresholds for C2 were higher (improved) both in patients (p<0.020) and in controls (p<0.0061) compared to after the placebo period. Among patients, the concentration needed to reach C2 (p<0.0004) and C5 (p<0.0009) increased after the period with the active substance compared to cough thresholds at baseline. The cough symptom scores improved after 4 weeks of active treatment (p<0.0030) compared to the baseline scores. Capsaicin powder taken orally decreased capsaicin cough sensitivity and cough symptoms. The findings suggest a desensitization of the cough-sensitive transient receptor potential vanilloid-1 (TRPV1).
Qutenza is a high-dose capsaicin patch used to relieve neuropathic pain from postherpetic neuralgia (PHN) and HIV-associated neuropathy (HIV-AN). In clinical studies, some patients had a dramatic response to the capsaicin patch. Our objective was to determine the baseline characteristics of patients who best benefit from capsaicin patch treatment. We conducted a meta-analysis of 6 completed randomized and controlled Qutenza studies by pooling individual patient data. Sustained response was defined as >50% decrease in the mean pain intensity from baseline to weeks 2 to 12, and Complete Response as an average pain intensity score=1 during weeks 2 to 12. Logistic regression was used to identify predictors of response and Complete Response, and subgroups of patients who respond best to the capsaicin patch. Baseline pain intensity score (BPIS)=4 was a predictor of Sustained and Complete Response in PHN and HIV-AN patients; absence of allodynia and presence of hypoesthesia, and a McGill Pain Questionnaire (MPQ) sensory score <22 were predictors of Sustained Response in PHN patients; female sex was a predictor of Sustained and Complete Response in HIV-AN patients. Thus, characteristics associated with the highest chance of responding to the capsaicin patch were, for PHN, BPIS=4, MPQ sensory score=22, absence of allodynia, and presence of hypoesthesia; for HIV-AN, they were female sex and BPIS=4. Patients with these characteristics had a statistically significantly greater chance of responding to the capsaicin patch than other patients.
For more Therapeutic Uses (Complete) data for CAPSAICIN (21 total), please visit the HSDB record page.

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Drug Warnings
A mild to moderate burning sensation is experienced following application and, in some patients, can be pronounced enough to require discontinuation of treatment.
/Capsaicin must be prevented/ from entering the eyes, open lesions, or mucous membranes.
... Capsaisin is for external use only. It should not be applied to wounds or to damaged or irritated skin. It should not be wrapped tightly. Capsaisin should not come in contact with mucous membranes, eyes, or contact lenses. If this occurs, the affected area should be rinsed thoroughly with water. This produc should be discontinued and a health care provider consulted if condition worsens or does not improve after regular use. If blistering occurs, or if severe burning persists. Heat should not be applied to the treated area immediately before or after applications, because this may increase the burning sensation. /Over the counter capsaicin/
Do not apply prescription capsaicin to the face or scalp to avoid risk of exposure to the eyes or mucous membranes.
For more Drug Warnings (Complete) data for CAPSAICIN (14 total), please visit the HSDB record page.

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Pharmacodynamics
Capsaicin is a TRPV1 receptor agonist. TRPV1 is a trans-membrane receptor-ion channel complex activated by temperatures higher than 43 degrees Celsius, pH lower than 6, and endogenous lipids. When activated by a combination of these factors, the channel can transiently open and initiate depolarization due to the influx of calcium and sodium ions. Because TRPV1 is commonly expressed in A-delta and mostly C fibers, depolarization results in action potentials which send impulses to the brain and spinal cord. These impulses result in capsaicin effects of warming, tingling, itching, stinging, or burning. Capsaicin also causes more persistent activation of these receptors compared to the environmental agonists, resulting in a loss of response to many sensory stimuli, described as "defunctionalization". Capsaicin is associated with many enzymatic, cytoskeletal, and osmotic changes, as well as disruption of mitochondrial respiration, impairing nociceptor function for extended periods of time.

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.)