MDR-652

MDR-652 is a highly specific and efficacious transient receptor potential vanilloid 1 (TRPV1) ligand with agonist activity. The Kis are 11.4 and 23.8 nM for hTRPV1 and rTRPV1, respectively. The EC50s are 5.05 and 93 nM for hTRPV1 and rTRPV1, respectively. Potent topical analgesic activity[1].

Signaling Pathways >> Membrane Transporter/Ion Channel >> TRP Channel

Research Areas >> Neurological Disease

hTRPV1:11.4 nM (Ki)

rTRPV1:23.8 nM (Ki)

hTRPV1:5.05 nM (EC50)

rTRPV1:93 nM (EC50)

MDR-652 (0.5 and 5 mg/kg) displays a dose-dependent decrease of body temperature, supporting that MDR-652 displays TRPV1 agonism in the intact animal[1]. MDR-652 (5-10 mg/kg; i.p. and s.c.) blocks the neuropathic pain completely, indicating 100% maximum possible effect (MPE) [1]. MDR-652 has a promising topical pharmacokinetic profile[1]. MDR-652 has no significant toxicity. In a single-dose toxicity study, the LD50 of MDR-652 is higher than 200 and 2000 mg/kg in i.p. and p.o. administration, respectively[1]. Animal Model: ICR mouse[1] Dosage: 0.5 and 5 mg/kg Administration: Administered intraperitoneally; 7 hours Result: Decreased body temperature in a dose-dependent manner. Animal Model: Rats with spinal nerve ligation (SNL) model[1] Dosage: 1, 2, 5, and 10 mg/kg Administration: Administered intraperitoneally and subcutaneously; 24 hours Result: 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.

[1]. Jihyae Ann, et al. Discovery of Nonpungent Transient Receptor Potential Vanilloid 1 (TRPV1) Agonist as Strong Topical Analgesic. J Med Chem. 2020 Jan 9;63(1):418-424.