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Year : 1973  |  Volume : 5  |  Issue : 3  |  Page : 349-373

Pharmacology of GABA-Like compounds in relation to the brain dopaminergic system


Correspondence Address:
I L Bonta


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Gamma-amino-butyric-acid (GABA). Received little attention until 1950 when its occurrence as a normal constituent of the central nervous system in mammal organism was established. There is little doubt today that the aminoacids CABA and glycine have in mammals the function to inhibit some central neuronal processes, while to glutamate, excitatory functions have been ascribed. Many investigators call these substances as neuromodulators but others denote them as neurotransmitters (Cooper, Bloom and Roth, 1970). The evidence, however, that these amino acids are transmitters according to criteria as applied to monoamines like noradrenaline or dopamine, is still inconclusive. When administered to an intract organism these aminoacids do not reach the central nervous system and their pharmacological importance remained largely limited to changes in their level or function after treatment with other agents. Pharmacological interest in the GABA-system was increased however after the observation that gamma-hydroxy- butyrate (GHB) (Roth and Suhr, 1970) -which being a GABA-metabolite is a normal component of brain tissue-after systematic administration has marked neuro-depressive properties along with important effects on dopaminergic nerve terminals. Such effects are also described for gamma-butyro-lacton (GBL) (Roth and Suhr, 1970), 1, 4-butanediol (Gessa, Spano, Vagiu , Grabai. Tagliamonte arid Mameli, 1968), a n d more recently for 1-hydroxy-3 aminopyrrolidone-2 (HR-966) (Bonta, Devos, Grijsen, Hillern, Noach and Sim, 1971), which are also chemically related to GABA. This chemical relation together with the combined property of neurodepression and selective influence on brain dopamine avoke pharmacological interest for the following reasons: I. To study the correlation between "eurosedation (motor hypokinesia, sleep) and dopaminergic mechanisms; II. To investigate the possibility of a functional connection between the GABA-system and the dopaminergic system; III. To explore the clinical implications of this new class of compounds.






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