Interactions between angiotensin II, diazepam, clonazepam and di-n-propylacetate in pentylenetetrazol kindling seizures in mice.
The effects of AT II alone and in combinations with the anticonvulsants diazepam, clonazepam and di-n-propylacetate (depakine) on PTZ-kindling in mice were studied. PTZ-kindling was provoked by intraperitoneal (i.p.) injections of PTZ (40 mg/kg) every other day in male albino mice until clonic seizures appeared. AT II in doses 0.1 and 1 microgram/mouse intracerebronventricularly (i.c.v.) decreased the intensity of seizures in PTZ-kindled mice. Diazepam (0.25 and 1 mg/kg i.p.), clonazepam (0.05 and 0.1 mg/kg i.p.) and depakine (75 mg/kg) inhibited PTZ-kindled seizures. Combinations of ineffective doses of AT II (0.05 microgram/mouse) and ineffective doses of diazepam (0.1 mg/kg) or clonazepam (0.01 mg/kg) or depakine (50 mg/kg) significantly decreased the intensity of seizures in PTZ-kindled mice. The seizure-decreasing effect of diazepam, clonazepam and depakine on PTZ-kindling in mice, which was potentiated by AT II, suggests interactions of AT II receptors with GABA and benzodiazepine receptors or with the GABA-benzodiazepine receptor-ionophore complex, probably effectuated through alsoteric mechanisms. A more efficient coupling of the GABA-benzodiazepine receptor-ionophore complex with AT II receptors might also be the reason for the decrease of the intensity of seizures in PTZ-kindled mice.
Georgiev
V P
VP
Department of Experimental Pharmacology, Bulgarian Academy of Science, Sofia.
Lazarova
M B
MB
Kambourova
T S
TS
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002998:Clonazepam / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation; D007476:Ionophores / Q000378:metabolism; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D010433:Pentylenetetrazole / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism; D012640:Seizures / Q000188:drug therapy*; D014635:Valproic Acid / Q000494:pharmacology
D007476:Ionophores; D011963:Receptors, GABA-A; D000804:Angiotensin II; D002998:Clonazepam; D014635:Valproic Acid; D003975:Diazepam; D010433:Pentylenetetrazole