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This study reports pharmacological and physiological effects of cis- and trans-(3-aminocyclopentanyl)butylphosphinic acid (cis- and trans-3-ACPBPA). These compounds are conformationally restricted analogs of the orally active GABA_B/C receptor antagonist (3-aminopropyl)-n-butylphosphinic acid (CGP36742 or SGS742). cis-[IC₅₀(ρ1) = 5.06 μM and IC₅₀(ρ2) = 11.08 μM; n = 4] and trans-3-ACPMPA [IC₅₀(ρ1) = 72.58 μM and IC₅₀(ρ2) = 189.7 μM; n = 4] seem competitive at GABA_C receptors expressed in Xenopus laevis oocytes, having no effect as agonists (1 mM) but exerting weak antagonist (1 mM) effects on human GABA_A and GABA_B receptors. cis-3-ACPBPA was more potent and selective than the trans-compound, being more than 100 times more potent at GABA_C than GABA_A or GABA_B receptors. cis-3-ACPBPA was further evaluated on dissociated rat retinal bipolar cells and dose-dependently inhibited …