4-Aminotetrolic Acid : New Conformational-restricted Analogue of γ-Aminobutyric Acid

摘要: RECENT studies strongly support a role for γ-aminobutyric acid (GABA) as an inhibitory transmitter at certain synapses in the mammalian central nervous system. Structure activity correlations of many GABA analogues implicate both intramolecular distance between zwitterionic centres and rotational freedom molecule important factors governing synaptic these substances1. The following observations provide pertinent information about active conformation(s) recognized by receptor. (1) Muscimol, isoxazole isolated from Amanita muscaria, seems to function analogue its action on neurones is comparable with that potency2 respect antagonism bicuculline3. Molecular orbital calculations suggest muscimol can assume similar conformations zwitterions charged (N+ 0−) least 5 and, more likely, 6 A apart4. (2) selective antagonist bicuculline exhibits some degree structural similarity particular muscimol3. (3) X-ray crystallography indicates exists partially folded conformation solid state5,6. (4) model receptor proposes adopts less than 4.4 centres7. Observations extended GABA, while conformations.