Affinity of various ligands for GABAA receptors containing alpha 4 beta 3 gamma 2, alpha 4 gamma 2, or alpha 1 beta 3 gamma 2 subunits.

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Scholze P, Ebert V, Sieghart W

Affinity of various ligands for GABAA receptors containing alpha 4 beta 3 gamma 2, alpha 4 gamma 2, or alpha 1 beta 3 gamma 2 subunits.

Eur J Pharmacol. 1996 May 23;304(1-3):155-62.

PubMed ID

8813598 [ View in PubMed

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Abstract

The potency of 30 benzodiazepine binding site ligands from 14 different structural classes for inhibition of [3H]Ro 15-4513 (ethyl-8-azido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4] benzodiazepine-3-carboxylate) binding to human embryonic kidney (HEK) 293 cells transiently transfected with alpha 4 beta 3 gamma 2S or alpha 1 beta 3 gamma 2S subunits of GABAA receptors was investigated. Most of these compounds were unable to significantly inhibit [3H]Ro 15-4513 binding to alpha 4 beta 3 gamma 2S receptors under conditions where they potently inhibited binding to alpha 1 beta 3 gamma 2S receptors. Nevertheless, compounds from four different structural classes were identified which exhibited a high affinity for alpha 4 beta 3 gamma 2S receptors. Variation of the structure of these compounds could lead to new ligands selectively interacting with alpha 4 beta 3 gamma 2S receptors. Compounds interacting with alpha 4 beta 3 gamma 2S receptor were also able to inhibit [3H]Ro 15-4513 binding to receptors consisting of alpha 4 gamma 2S subunits with comparable potency. These results support the conclusion that the alpha subunit is a major determinant of the benzodiazepine binding site properties of GABAA receptors containing alpha and gamma subunits.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Flumazenil	Gamma-aminobutyric acid receptor subunit alpha-1	Ki (nM)	2.9	N/A	N/A	Details
Zolpidem	Gamma-aminobutyric acid receptor subunit alpha-1	Ki (nM)	41	N/A	N/A	Details