Potentiation by glycine of anticonvulsant drugs in maximal electroshock seizures in rats.
This study evaluated the potentiation by glycine of anticonvulsant drugs in maximal electroshock seizures in rats. Administered alone, glycine (40 mmol/kg, p.o.) induced no anticonvulsant effect or neurotoxicity. Administered together with the anticonvulsants, glycine significantly enhanced the anticonvulsant potency of phenobarbital and carbamazepine. Glycine also potentiated the anticonvulsant actions of MK-801 and diazepam but did not improve the selectivity of the drugs, as effective doses were still associated with neurotoxicity. Glycine did not potentiate phenytoin or sodium divalproate. Administration together with glycine had no significant effect on the concentrations of phenobarbital or carbamazepine in the brain. Administration together with phenobarbital had no relevant effect on the concentration of glycine in the brain but administration of glycine and carbamazepine together resulted in an increased concentration of glycine in the hippocampus and brainstem. These findings indicate a possible glycine-sensitive component in the mechanism of action of phenobarbital, carbamazepine and diazepam in maximal electroshock seizures. Although the mechanism may not be mediated by a glycine-GABA interaction, the evidence does implicate a possible interaction between glycine and anticonvulsant drugs at NMDA receptors.
Peterson
S L
SL
Department of Medical Pharmacology and Toxicology, Texas A&M University, College Station 77843.
Trzeciakowski
J P
JP
Frye
G D
GD
Adams
H R
HR
D000818:Animals; D000927:Anticonvulsants / Q000378:metabolism / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects; D002220:Carbamazepine / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003975:Diazepam / Q000494:pharmacology; D004347:Drug Interactions; D004357:Drug Synergism; D004597:Electroshock; D005998:Glycine / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D009422:Nervous System Diseases / Q000139:chemically induced; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000503:physiopathology*; D013654:Taurine / Q000097:blood / Q000378:metabolism
D000927:Anticonvulsants; D013654:Taurine; D002220:Carbamazepine; D003975:Diazepam; D005998:Glycine; D010634:Phenobarbital