A STUDY OF GABA AND ITS ANALOGS USING THE MOLECULAR-ORBITAL METHOD

GABA is a major neurotransmitter in the central nervous system. Data o n GABA and its analogues calculated by using the ab initio and the MND O method were compared with data obtained experimentally. The structur es of GABA analogues calculated by the ab initio method agree well wit h the experimental data. This finding suggests the high reliability of this method. However, the structures of GABA analogues calculated by the MNDO method reflect only some aspects of the experimental data. Th erefore the MNDO method should be used only for carefully selected che mical compounds. The amino group in GABA and its analogues was proved to be the major active site. The electrostatic potential around the am ino group in these compounds seems to be related to their biological a ctivity. The difference in the electrostatic potential between the rec eptor binding molecules and the neuronal uptake molecules suggests tha t the structure of post-synaptic receptors might differ from that of u ptake receptors. This finding suggests that there are at least two GAB A-A receptors. GABA molecules seem to have a high potential for bindin g to the two receptors because they are highly flexible and can readil y change their conformation. These results indicate a high reliability of the data calculated by the molecular orbital method and suggest th at this method provides us with useful information that cannot be obta ined experimentally.