Molecular Conformation of GABA

Abstract

CURTIS et al.^1,2 have described evidence suggesting that the alkaloid bicuculline is a specific antagonist to the action of γ-aminobutyric acid (GABA), a possible inhibitory transmitter in the mammalian brain^3,4. By considering structural models, they suggested³ as a stereochemical basis for this antagonism a geometrical configuration in which the N and Ol=C1—O2 of GABA is isosteric with the N and C2—Cl—Ol in bicuculline (Fig. 1a and b). An alternative configuration of GABA, which would give a greater degree of stereochemical similarity to bicuculline, is depicted in Fig. 1c. In both molecules the N is now seen to be isosterically related to Ol=Cl—O2 and located at an angle of about 40° to the plane of the O=Cl—O group viewed towards C2 (Fig. 2). In contrast to Curtis's suggestion, there is now not only geometrical congruence but also identical matching of atomic species.