MDR-652 is a highly specific and efficacious agonist of nonpungent transient receptor potential vanilloid 1 (TRPV1), with Ki values of 11.4 nM and 23.8 nM for hTRPV1 and rTRPV1, respectively, and EC50s of 5.05 nM and 93 nM for hTRPV1 and rTRPV1, respectively. MDR-652 is a potent topical analgesic.

TRPV1 (rat):93 nM (EC50), TRPV1 (rat):23.8 nM (Ki), TRPV1 (human):11.4 nM (Ki), TRPV1 (human):5.05 nM (EC50)

MDR-652 (0.5 and 5 mg/kg) demonstrates a dose-dependent decrease in body temperature, indicating TRPV1 agonism in intact animals[1]. It exhibits potent analgesic activity in neuropathic pain models and blocks capsaicin-induced allodynia, with dermal accumulation and minimal transdermal absorption. At 5-10 mg/kg (i.p. and s.c.), MDR-652 completely inhibits neuropathic pain, achieving 100% maximum possible effect (MPE)[1]. MDR-652 has a promising topical pharmacokinetic profile, shows weak systemic toxicity, and is negative in genotoxicity assays. In a single-dose toxicity study, the LD50 of MDR-652 exceeds 200 mg/kg (i.p.) and 2000 mg/kg (p.o.)[1].

MDR-652 (0.5 and 5 mg/kg; Administered intraperitoneally; 7 hours; ICR mouse) decreased body temperature in a dose-dependent manner. MDR-652 (1, 2, 5, and 10 mg/kg; Administered intraperitoneally and subcutaneously; 24 hours; Rats with spinal nerve ligation (SNL) model)The i.p. administration exhibited an excellent and dose dependent analgesic profile with an ED50 of 0.5-2 mg/kg. The subcutaneous injection (sc) also displayed an excellent analgesic outcome with maximum effect at 30 min after administration.