The gamma-aminobutyrate content of nerve endings (synaptosomes) in mice after the intramuscular injection of gamma-aminobutyrate-elevating agents: a possible role in anticonvulsant activity.
The intramuscular administration of L-cycloserine, gabaculine, and aminooxyacetic acid caused significant, time-dependent increases in the gamma-aminobutyric acid (GABA) content of both whole brain and synaptosomal-enriched preparations obtained from the tissue, a linear relationship being observed between the two parameters. In contrast, the administration of hydrazine resulted in a large increase in whole brain GABA level, with little change in the synaptosomal GABA content. The key factor in these different responses appeared to be the degree of inhibition of glutamic acid decarboxylase by the drugs. Pretreatment of mice with the GABA-elevating agents resulted in a delay in the onset of seizures, which was related directly to the increase in synaptosomal GABA content. Although the seizures were delayed, they occurred while the GABA content of nerve endings (synaptosomes) was above that in preparations from untreated animals. The decrease in GABA content at the onset of seizures, expressed as a percentage of the level at the time of injection of the convulsant agent, was, however, reasonably constant. A hypothesis to explain these results is proposed.
D000085:Acetates / Q000494:pharmacology*; D000625:Aminooxyacetic Acid / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants; D001921:Brain / Q000378:metabolism*; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D003514:Cyclohexylamines / Q000494:pharmacology; D003523:Cycloserine / Q000494:pharmacology*; D006834:Hydrazines / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051379:Mice; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000085:Acetates; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D003514:Cyclohexylamines; D006834:Hydrazines; D000625:Aminooxyacetic Acid; C012987:gabaculine; D005680:gamma-Aminobutyric Acid; D003523:Cycloserine