Does homocarnosine mediate the dyskinetic movements induced by gaba-transaminase inhibitors.
Unilateral application of gamma-aminobutyric acid (GABA) antagonists on the motor cortex of conscious rats produces myoclonic movements. Paradoxically, the same behaviour can be observed with high concentrations of some GABA-transaminase (GABA-T) inhibitors. Since the GABA conjugate homocarnosine is increased in the brain following GABA-T inhibition and since homocarnosine is known to displace [3H]-GABA from its binding sites at high concentration, we investigated whether homocarnosine might explain the dyskinetic movements produced by these GABA-T inhibitors. We found that homocarnosine produces dyskinesia similar to that observed with GABA antagonists and GABA-T inhibitors when applied directly to the cortex. However, this property of homocarnosine is unlikely to be the basis of the dyskinetic effect of GABA-T inhibitors since we found no relationship between brain homocarnosine levels and the appearance of abnormal movements following GABA-T inhibition.
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors; D000818:Animals; D001640:Bicuculline / Q000008:administration & dosage / Q000494:pharmacology; D002336:Carnosine / Q000031:analogs & derivatives / Q000378:metabolism*; D004151:Dipeptides / Q000378:metabolism*; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism*; D007276:Injections, Intraventricular; D010852:Picrotoxin / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats
D000612:4-Aminobutyrate Transaminase; D001640:Bicuculline; D002336:Carnosine; D004151:Dipeptides; D010852:Picrotoxin; C005038:homocarnosine