Add time:09/24/2019         Source:sciencedirect.com

Ethyl 2-(4-bromophenyl)-1-(2,4-dichlorophenyl)-1H-4-imidazolecarboxylate (TG41) enhanced the binding both of γ-aminobutyric acid (GABA) and of flunitrazepam to rat cerebral cortical membranes. Electrophysiological recordings from Xenopus oocytes expressing various recombinant GABAA receptor subtypes revealed that TG41 enhanced the function of all receptor subunit combinations tested. The potency of TG41 at receptors containing α1, β2, and γ2L subunits was greater than that of alphaxalone, etomidate, propofol, or pentobarbital. The potency of TG41 was also greater at receptors containing α1 or α2 subunits than at those containing α4 and it was markedly higher at receptors containing β2 or β3 subunits than at those containing β1. This drug induced a reversible loss of the righting reflex in Xenopus tadpoles and it elicited hypnosis (5 mg/kg) after intravenous administration in rats. These results indicate that the pharmacological profile of TG41 is similar to that of general anesthetics which potentiate the activity of GABAA receptors containing the β2 or β3 subunit.

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