Diazepam potentiation by glycine in pentylenetetrazol seizures is antagonized by 7-chlorokynurenic acid.

Abstract

This study evaluated a possible mechanism by which glycine potentiates the activity of diazepam (DZP) and valproic acid (VAL) against the clonic seizures induced by pentylenetetrazol (PTZ) in rats. Neither 7-chlorokynurenic acid (7-CLKYNA) nor strychnine in doses of 10, 50, or 100 nmol ICV significantly altered the clonic seizure response to PTZ. However, 7-CLKYNA (100 nmol, ICV), but not strychnine (100 nmol, ICV), antagonized the anticonvulsant activity induced by coadministration of DZP (1.0 mg/kg, IP) and glycine (40 mmol/kg, PO). Neither 7-CLKYNA (100 nmol, ICV) nor strychnine (100 nmol, ICV) significantly altered the anticonvulsant activity induced by coadministration of VAL and glycine. 7-CLKYNA (100 nmol, ICV) had no effect on the anticonvulsant activity of DZP or VAL in the absence of glycine. These results provide evidence that the glycine potentiation of the anticonvulsant activity of DZP in clonic seizures induced by PTZ may be mediated by the strychnine-insensitive glycine receptor.

• Authors: S L Peterson
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 47 Issue 2 Pg. 241-6 (Feb 1994) ISSN: 0091-3057 [Print] United States
• PMID: 8146214 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Receptors, Glycine
• Receptors, N-Methyl-D-Aspartate
• Kynurenic Acid
• Strychnine
• Diazepam
• 7-chlorokynurenic acid
• Glycine
• Pentylenetetrazole

Topics

• Animals
• Diazepam (pharmacology)
• Drug Synergism
• Glycine (antagonists & inhibitors, pharmacology)
• Injections, Intraventricular
• Kynurenic Acid (administration & dosage, analogs & derivatives, pharmacology)
• Male
• Pentylenetetrazole
• Rats
• Rats, Sprague-Dawley
• Receptors, Glycine (drug effects)
• Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors)
• Seizures (chemically induced, prevention & control)
• Strychnine (administration & dosage, pharmacology)