3-[2-Cyano-3-(trifluoromethyl)phenoxy]phenyl-4,4,4-trifluoro-1-butanesulfonate (BAY 59-3074) is a novel, selective cannabinoid CB 1 /CB 2 receptor ligand (K i ϭ 55.4, 48.3, and 45.5 nM at rat and human cannabinoid CB 1 and human CB 2 receptors, respectively), with partial agonist properties at these receptors in guanosine 5- [␥ 35 S]-thiophosphate triethyl-ammonium salt ([ 35 S]GTP␥S) binding assays. In rats, generalization of BAY 59-3074 to the cue induced by the cannabinoid CB 1 receptor agonist (Ϫ)-(R)-3-(2-hydroxymethylindanyl-4-oxy)phenyl-4,4,4-trifluoro-1-butanesulfonate (BAY 38-7271) in a drug discrimination procedure, as well as its hypothermic and analgesic effects in a hot plate assay, were blocked by the cannabinoid CB 1 receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride (SR 141716A). BAY 59-3074 (0.3-3 mg/kg, p.o.) induced antihyperalgesic and antiallodynic effects against thermal or mechanical stimuli in rat models of chronic neuropathic (chronic constriction injury, spared nerve injury, tibial nerve injury, and spinal nerve ligation models) and inflammatory pain (carrageenan and complete Freund's adjuvant models). Antiallodynic efficacy of BAY 59-3074 (1 mg/kg, p.o.) in the spared nerve injury model was maintained after 2 weeks of daily administration. However, tolerance developed rapidly (within 5 days) for cannabinoid-related side effects, which occur at doses above 1 mg/kg (e.g., hypothermia). Uptitration from 1 to 32 mg/kg p.o. (doubling of daily dose every 4th day) prevented the occurrence of such side effects, whereas antihyperalgesic and antiallodynic efficacy was maintained/increased. No withdrawal symptoms were seen after abrupt withdrawal following 14 daily applications of 1 to 10 mg/kg p.o. It is concluded that BAY 59-3074 may offer a valuable therapeutic approach to treat diverse chronic pain conditions.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.