Synergistic anticonvulsant effects of GABA-T inhibitors and glycine.
The anticonvulsant effect of inhibitors of GABA-T (R/S-gamma-vinyl-GABA, ethanolamine-O-sulfate, gabaculine, aminooxyacetic acid) was enhanced by 10 mmol/kg glycine in animal seizure models which are based on a functional GABA deficit. Similar to glycine in their action, although less effective, were its close structural analogues (sarcosine, N,N-dimethylglycine) and homologous omega-aminoacids (beta-alanine, taurine, gamma-aminobutyric acid, delta-aminovaleric acid). It is assumed that glycine and its structural analogues act on supraspinal glycine receptors as glycine agonists. Our observation is the first example of the synergistic interaction of two inhibitory neuronal systems resulting in the amplification of the anticonvulsant effect. Combined treatment with GABA-T inhibitors and glycine may turn out to be of practical importance in the therapy of seizure disorders and other diseases, for which treatment with GABA-T inhibitors is considered a potentially useful therapeutic approach.
D015097:3-Mercaptopropionic Acid / Q000494:pharmacology; D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors*; D000596:Amino Acids / Q000494:pharmacology; D000614:Aminocaproates / Q000494:pharmacology; D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D004357:Drug Synergism; D004983:Ethanolamines / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole / Q000494:pharmacology; D010852:Picrotoxin / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D054830:Sesterterpenes; D013331:Strychnine / Q000494:pharmacology; D020888:Vigabatrin
D015097:3-Mercaptopropionic Acid; D000612:4-Aminobutyrate Transaminase; D000596:Amino Acids; D000614:Aminocaproates; D000625:Aminooxyacetic Acid; D000927:Anticonvulsants; D001640:Bicuculline; D004983:Ethanolamines; D005998:Glycine; D010433:Pentylenetetrazole; D010852:Picrotoxin; D054830:Sesterterpenes; D013331:Strychnine; D020888:Vigabatrin; C020619:ethanolamine O-sulfate; C022961:picrotoxinin