GABA/BZ-and NMDA-receptor interaction in digoxin-induced convulsions in rats.
Digoxin (7.5 micrograms icv) induced 'pop-corn' type of convulsions and 100% mortality. The GABA-ergic agents produced varying degree of protection against digoxin-induced neurotoxicity. Diazepam (4 mg/kg) offered significant protection whereas pentobarbital (5 mg/kg) and baclofen (5 mg/kg) markedly reduced per cent mortality, but ethanol (2 g/kg), progabide (50 mg/kg) and muscimol (0.5 mg/kg) as well as GABA (50 mg/kg) could not offer significant protection in doses used. GABA-ergic agonists; GABA, baclofen, diazepam and pentobarbital when administered along with MK-801 (0.5 mg/kg) a non-competitive NMDA antagonist, a potentiation of anticonvulsant action of MK-801 was observed. MK-801 showed potent anticonvulsant profile in dose range (0.25-1 mg/kg) studied. A synergistic influence of Mg2+ and K+ ions on NMDA receptor antagonism was also observed. A role of GABA-ergic facilitation and NMDA antagonism as a potential anticonvulsant approach in digoxin-induced convulsions in rats has been suggested.
Gautam
S K
SK
Department of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Kulkarni
S K
SK
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004077:Digoxin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005260:Female; D007276:Injections, Intraventricular; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D012492:Salts / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000494:pharmacology
D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D012492:Salts; D009118:Muscimol; C017985:progabide; D005680:gamma-Aminobutyric Acid; D016291:Dizocilpine Maleate; D004077:Digoxin; D001418:Baclofen; D010424:Pentobarbital; D003975:Diazepam