EFFECTS OF THE IRREVERSIBLE INHIBITION OF GABA TRANSAMINASE UPON SOME MORPHINE EFFECTS

The effects were investigated of two irreversible inhibitors of gamma-aminobutyric acid (GABA) transaminase on the analgesic response to morphine, on the intensity of tolerance produced by a slow release preparation of the opiate and on the degree of physical dependence to the analgesic. Both compounds, γ-acetylenic GABA and γ-vinyl GABA, produced an intensification of morphine analgesia, although large doses of γ-acetylenic GABA produced stimulant effects that masked a possible synergism. The intensification of analgesia was greater in tolerant mice as compared with the increment observed in naive animals, which may indicate a decrease in the intensity of tolerance, since the drugs per se were ineffective in the analgesic test. Physical dependence was attenuated by the two compounds assayed, except when γ-acetylenic GABA was administered in high doses. The results may indicate a relationship between some acute and chronic effects of morphine and GABA concentration in the nervous tissue. However an effect of the GABA transaminase inhibitors unrelated to GABA levels in the nervous system cannot be dismissed. © 1979.