GABA Receptor Antagonist

GABA (γ-aminobutyric acid) is the main inhibitory neurotransmitter in the mammalian central nerve system and GABA_A, GABA_B, and GABA_C receptors have been identified as the major receptors.¹⁾ GABA_A and GABA_C receptors are members of transmitter-gated ion channels, and GABA_B receptors are the receptors that are coupled to G-protein and activate secondary messenger systems and Ca²⁺ and K⁺ ion channels.¹⁾
Bicuculline (1) is a phthalide isoquinoline alkaloid isolated from a variety of plants, Dicentra, Corydalis, and Adlumia, genera of the Fumariaceae family. GABA_A receptors are selectively blocked by 1.^1-3) Affinity of 1 and the receptors have been studied by using mutational forms of recombinant receptor proteins.³⁾ 1 and its quaternary salts also have actions other than as GABA-receptor antagonists including inhibition of cholinesterase, effects on 5-HT₃, nicotinic, and N-methyl-D-aspartate (NMDA) receptors.^2,3)