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

TRPV1 antagonist 3 (Compound 7q) is highly selective for the TRPV1 receptor relative to other TRP channels [1]. TRPV1 antagonist 3 shows acceptable aqueous solubility (solubility at pH 7.4 = 26 μg/mL) [1].

TRPV1 antagonist 3 (Compound 7q) (0-30 mg/kg; i.p.; 30 min) shows anti-nociceptive effect mainly mediated by blocking CAP-activated channel [1]. TRPV1 antagonist 3 (0-100 mg/kg; i.g.) had no obvious thermal effect in rats [1]. TRPV1 antagonist 3 (10 mg/kg; i.v.) shows a good concentration in the brain at 0.5 h, with value of 2311 ng/g, and has good CNS penetration, with a brain/plasma ratio of 1.66 [1]. Animal Model: KM male mice (18-22 g), capsaicin, acetic acid, and thermal induced pain model [1] Dosage: 3, 10, and 30 mg/kg. 20 μL of solution of capsaicin (16 mg/20 mL) was injected s.c. under the skin of the dorsal surface of the right hind paw, or injected with 0.6% acetic acid (0.1 mL/10 g/mouse i.p.). Administration: Intraperitoneally administration; 30 min Result: In capsaicin-induced nociception, licking time decreased significantly in a dose-dependent manner. In acid-induced nociception, no significant anti-nociceptive activities were found compared with the control (SB-705498 and BCTC) at all dosage. In thermal-induced nociception, the latency time of nociceptive responses was increased at the doses of 10 and 30 mg/kg. Animal Model: Spragur-Dawley male rats (220-250 g) [1] Dosage: 10 mg/kg or 20 mg/kg Administration: Intravenous injection of 10 mg/kg or oral dose of 20 mg/kg (Pharmacokinetic Analysis) Result: In vivo pharmacokinetic parameters of TRPV1 antagonist 3 in rats (n=3) [1] Parameters IV PO t 1/2 (h) 0.106 ± 0.076 t 1/2, ka (h) 0.462 ± 0.096 t 1/2, k 10 (h) 0.527 ± 0.106 k a (1/h) 1.65 ± 0.364 k 10 (1/h) 12.076 ± 2.337 1.133 ± 0.358 V (L/kg) 0.003 ± 0.001 0.016 ± 0.006 CL (L/h/kg) 0.024 ± 0.013 0.022 ± 0.01 T max (h) 0.711 ± 0.144 C max (ng/mL) 311.377 ± 108.017 AUC 0-inf (ng/mL*h) 495.955 ± 214.634 598.873 ± 212.319 MRT (h)