Synthetic peripherally-restricted cannabinoid suppresses chemotherapy-induced peripheral neuropathy pain symptoms by CB1 receptor activation.

Synthetic peripherally-restricted cannabinoid suppresses chemotherapy-induced peripheral neuropathy pain symptoms by CB1 receptor activation. Neuropharmacology. 2018 Jul 04;: Authors: Mulpuri Y, Marty VN, Munier JJ, Mackie K, Schmidt BL, Seltzman HH, Spigelman I Abstract Chemotherapy-induced peripheral neuropathy (CIPN) is a severe and dose-limiting side effect of cancer treatment that affects millions of cancer survivors throughout the world and current treatment options are extremely limited by their side effects. Cannabinoids are highly effective in suppressing pain symptoms of chemotherapy-induced and other peripheral neuropathies but their widespread use is limited by central nervous system (CNS)-mediated side effects. Here, we tested one compound from a series of recently developed synthetic peripherally restricted cannabinoids (PRCBs) in a rat model of cisplatin-induced peripheral neuropathy. Results show that local or systemic administration of 4-{2-[-(1E)-1[(4-propylnaphthalen-1-yl)methylidene]-1H-inden-3-yl]ethyl}morpholine (PrNMI) dose-dependently suppressed CIPN mechanical and cold allodynia. Orally administered PrNMI also dose-dependently suppressed CIPN allodynia symptoms in both male and female rats without any CNS side effects. Co-administration with selective cannabinoid receptor subtype blockers revealed that PrNMI's anti-allodynic effects are mediated by CB1 receptor (CB1R) activation. Expression of CB2Rs was reduc...
Source: Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Neuropharmacology Source Type: research