Ethyl 2-(4-bromophenyl)-1-(2,4-dichlorophenyl)-1H-4-imidazolecarboxylate (TG41) enhanced the binding both of gamma-aminobutyric acid (GABA) and of flunitrazepam to rat cerebral cortical membranes. Electrophysiological recordings from Xenopus oocytes expressing various recombinant GABA(A) receptor subtypes revealed that TG41 enhanced the function of all receptor subunit combinations tested. The potency of TG41 at receptors containing alpha 1, beta 2, and gamma 2L subunits was greater than that of alphaxalone, etomidate, propofol, or pentobarbital. The potency of TG41 was also greater at receptors containing alpha 1 or alpha 2 subunits than at those containing alpha 4 and it was markedly higher at receptors containing beta 2 or beta 3 subunits than at those containing beta 1. 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 GABA(A) receptors containing the beta 2 or beta 3 subunit. (c) 2005 Elsevier B.V. All rights reserved.
Ethyl 2-(4-bromophenyl)-1-(2,4-dichlorophenyl)-1H-4-imidazolecarboxylate is a novel positive modulator of GABA(A) receptors
BUSONERO, FABIO;TALANI, GIUSEPPE;SANNA, ENRICO;
2005-01-01
Abstract
Ethyl 2-(4-bromophenyl)-1-(2,4-dichlorophenyl)-1H-4-imidazolecarboxylate (TG41) enhanced the binding both of gamma-aminobutyric acid (GABA) and of flunitrazepam to rat cerebral cortical membranes. Electrophysiological recordings from Xenopus oocytes expressing various recombinant GABA(A) receptor subtypes revealed that TG41 enhanced the function of all receptor subunit combinations tested. The potency of TG41 at receptors containing alpha 1, beta 2, and gamma 2L subunits was greater than that of alphaxalone, etomidate, propofol, or pentobarbital. The potency of TG41 was also greater at receptors containing alpha 1 or alpha 2 subunits than at those containing alpha 4 and it was markedly higher at receptors containing beta 2 or beta 3 subunits than at those containing beta 1. 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 GABA(A) receptors containing the beta 2 or beta 3 subunit. (c) 2005 Elsevier B.V. All rights reserved.
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