TRPV1 antagonist 3

TRPV1 antagonist 3 (Compound 7q) is a highly potent TRPV1 receptor antagonist with an IC50 of 2.66 nM against capsaicin. It exhibits selectivity in its mode of action, is orally bioavailable (60%), and can penetrate the central nervous system [1].

TRPV1 (human):2.66 nM, TRPM8:7.45 μM

TRPV1 antagonist 3 (Compound 7q) exhibits high selectivity for the TRPV1 receptor over other TRP channels and demonstrates acceptable aqueous solubility, measuring 26 μg/mL at pH 7.4 [1].

TRPV1 antagonist 3 (Compound 7q), administered intraperitoneally (0-30 mg/kg; 30 min before testing), exhibits significant anti-nociceptive effects primarily by inhibiting the capsaicin (CAP)-activated channel, with no evident thermal impact when given orally (0-100 mg/kg). A notable concentration of 2311 ng/g was observed in the brain 0.5 hours after intravenous administration (10 mg/kg), indicating effective central nervous system (CNS) penetration, evidenced by a brain/plasma ratio of 1.66. In experiments involving KM male mice (18-22 g) subjected to capsaicin, acetic acid, and thermal pain models, results showed a dose-dependent decrease in licking time in capsaicin-induced pain and an increase in latency time for thermal-induced nociceptive responses at doses of 10 and 30 mg/kg. However, no significant anti-nociceptive activity was observed in acid-induced pain compared to controls. Pharmacokinetic analysis in Sprague-Dawley male rats (220-250 g) following either intravenous (10 mg/kg) or oral (20 mg/kg) administration revealed various absorption and elimination parameters, demonstrating the compound's favorable pharmacokinetics, including a half-life suggesting rapid clearance from the body.