Analogues of Glutamic and γ-Amino-n-butyric acids having Potent Actions on Mammalian Neurones

Abstract

NUMEROUS investigations have shown that certain amino-acids, including several which are present in the mammalian central nervous system, strongly influence the behaviour of neurones when applied extracellularly^1–4. These amino-acids fall into two groups; neutral amino-acids related to γ-amino-n-butyric acid (GABA), which depress the activity of neurones, and acidic amino-acids related to glutamic acid, which excite neurones³. An analysis of the effects of these substances on mammalian spinal neurones indicates that whereas the mechanism of action of GABA differs from that of mammalian inhibitory transmitters⁵, the action of L-glutamie acid has certain features in common with that of excitatory transmitter substances^3,6. Recently, several substances were found to have a much greater potency than GABA and glutamic acid as depressants and excitants respectively of neurones within the isolated and sagitally hemisected spinal cord of the toad⁷. In particular, N-methylaspartic acid and homocysteic acid were found to be potent excitants, and 3-amino-1-propanesulphonic acid was a powerful depressant. The potencies of these and related amino-acids on mammalian spinal and cortical neurones have now been determined.