Capsaicin is a topical analgesic that is FDA approved for the treatment of neuropathic pain associated with postherpetic neuralgia. Capsaicin is most often used as a topical analgesic and exists in many formulations of cream, liquid, and patch preparations of various strengths; however, it may also be found in some dietary supplements. Capsaicin is a naturally-occurring botanical irritant in chili peppers, synthetically derived for pharmaceutical formulations. Capsaicin is an agonist for the transient receptor potential vanilloid I receptor (TRPVI), which is an ion channel-receptor complex expressed on nociceptive nerve fibers in the skin. Common adverse reactions include erythema, rash, pruritus, nausea.

ABT-102 is a selective antagonist of transient receptor potential vanilloid type 1 (TRPV1), designed for the treatment of nociceptive pain. ABT-102 potently blocks multiple modes of TRPV1 receptor activation and effectively attenuates downstream consequences of receptor activity.

AMG-517, a potent and selective vanilloid receptor (VR1) antagonist, was in clinical trials with Amgen for the treatment of pain. AMG 517 inhibits CAP- (500 nM), acid- (pH 5.0), or heat-(45 °C) induced 45Ca2+ influx into human TRPV1-expressing CHO Cells with IC50 of 0.76 nM, 0.62 nM and 1.3 nM. AMG-517 blocks capsaicin-, proton-, and heat-induced inward currents in TRPV1-expressing cells similarly. AMG-517 inhibits native TRPV1 activation by capsaicin in rat dorsal root ganglion neurons with an IC50 value of 0.68 nM. Oral administration of AMG-517 produces a dose-dependent increase in plasma concentrations, it also produces a dose-dependent decrease in the number of flinches induced by capsaicin treatment. The minimally effective dose (MED), based on a statistically significant difference in number of flinches from the vehicle versus capsaicin-administered group, is 0.3 mg/kg for AMG 517. The corresponding plasma concentrations are 90 to 100 ng/mL for AMG-517. AMG-517 (3 mg/kg) exhibits significant reductions in capsaicin-induced flinch up to 24 h after dosing. AMG 517 blocks thermal hyperalgesia in CFA model of pain. Unfortunately, clinical studies of AMG-517 were discontinued due to the hyperthermia observed after exposure to single and multiple doses.

Dihydrocapsaicin is a capsaicinoid and analog and congener of capsaicin in chili peppers. Like capsaicin, it contributes to the spicy taste of chili peppers, although it is less potent than capsacian. Dihydrocapsaicin has been shown to induce hypothermia in rats, a property which may help protect victims of stroke and cardiac arrest.