Article date: 1985/1/1
PubMed ID: 2932364
Journal name: General pharmacology (ISSN: 0306-3623)
THPO, a GABA uptake inhibitor, when given in doses of up to 4 mmol/kg (i.p.) to mice, had only a marginal protective effect against seizures induced 1 hr later by 3-mercaptopropionic acid (MPA). THPO (4 mmol/kg), when given in combination with 10 mmol/kg of glycine, protected 60% of the mice from MPA-induced convulsions. The combination of THPO and glycine delayed the onset of metrazol-induced clonic convulsions and protected 30% of the animals from seizures, although neither glycine or THPO alone had a significant anticonvulsant effect against metrazol induced seizures. In agreement with earlier findings, the results presented in this work seem to indicate that the synergistic anticonvulsant effects of glycine and GABAergic agents are independent of their mode of action: the effects of GABA agonists (muscimol) GABA-T inhibitors (vinylGABA), or an inhibitor of glial GABA uptake (THPO) are similarly amplified by glycine.
Author List: Seiler N, Sarhan S, Krogsgaard-Larsen P, Hjeds H, Schousboe A
Publication Types: Journal Article; Research Support, Non-U.S. Gov't
Substances mentioned in the article: Anticonvulsants; Isoxazoles; Neurotransmitter Uptake Inhibitors; Oxazoles; 4,5,6,7-tetrahydroisoxazolo(4,5-c)pyridin-3-ol; gamma-Aminobutyric Acid; 3-Mercaptopropionic Acid; Glycine; Pentylenetetrazole;
Mesh terms: 3-Mercaptopropionic Acid; Animals; Anticonvulsants; Brain Chemistry/drug effects; Drug Synergism; Glycine/metabolism; Isoxazoles/metabolism; Male; Mice; Neurotransmitter Uptake Inhibitors/metabolism; Oxazoles/pharmacology; Pentylenetetrazole; Seizures/chemically induced; gamma-Aminobutyric Acid/physiology;