The α6 subunit-containing GABAA receptor: A novel drug target for inhibition of trigeminal activation.

We examined effects of these compounds on both central and peripheral TGVS responses induced by i.c. capsaicin. Compound 6 (3-10 mg/kg, i.p.) significantly attenuated the TCC neuronal activation and TG CGRP-ir elevation, and dural CGRP depletion induced by capsaicin. All these effects of Compound 6 were mimicked by topiramate, Ro15-4513 and loreclezole, but not by diazepam. The brain-impermeable furosemide antagonized the peripheral, but not central, effects of Compound 6. These results suggest that the α6GABAAR in TG is a novel drug target for TGVS activation and that α6GABAAR-selective PAMs have the potential to be developed as a novel pharmacotherapy for migraine.
PMID: 30016665 [PubMed - as supplied by publisher]

Source: Neuropharmacology - July 14, 2018 Category: Drugs & Pharmacology Authors: Fan PC, Lai TH, Hor CC, Lee MT, Huang P, Sieghart W, Ernst M, Knutson DE, Cook J, Chiou LC Tags: Neuropharmacology Source Type: research