Alpidem is an anxiolytic agent.1 It selectively binds to α1β2γ2 subunit-containing GABAA receptors over α5β2γ2 subunit-containing GABAA receptors in HEK293 cells (IC50s = 0.017 and ≥10 µM, respectively, for the recombinant rat receptors).2 Alpidem also binds to the GABAA/benzodiazepine receptor complex and translocator protein 18 kDa (TSPO) with IC50 values of 0.028 and 0.0079 µM, respectively.3 It reduces marble burying in mice, indicating anxiolytic activity, with a minimum effective dose (MED) of 10 mg/kg.4 Unlike the benzodiazepine alprazolam, alpidem does not induce sedation in mice when administered at doses up to 2 mg/kg.5 Formulations containing alpidem have previously been used in the treatment of generalized anxiety disorder.
1.Skolnick, P.Anxioselective anxiolytics: On a quest for the holy grailTrends Pharamacol. Sci.33(11)611-620(2012) 2.Faure-Halley, C., Graham, D., Arbilla, S., et al.Expression and properties of recombinant α1β2γ2 and α5β2γ2 forms of the rat GABAA receptorEur. J. Pharmacol.246(3)283-287(1993) 3.Trapani, G., Franco, M.C., Ricciardi, L., et al.Synthesis and binding affinity of 2-phenylimidazo[1,2-alpha]pyridine derivatives for both central and peripheral benzodiazepine receptors. A new series of high-affinity and selective ligands for the peripheral typeJ. Med. Chem.40(19)3109-3118(1997) 4.Zivkovic, B., Morel, E., Joly, D., et al.Pharmacological and behavioral profile of alpidem as an anxiolyticPharmacopsychiatry23(Suppl. 3)108-113(1990) 5.HascoËt, M., and Bourin, M.Anticonflict effect of alpidem as compared with the benzodiazepine alprazolam in ratsPharmacol. Biochem. Behav.56(2)317-324(1997)