Further evidence for the interactions between angiotensin II and GABAergic transmission in pentylenetetrazol kindling seizures in mice.
The effects of the GABAergic drugs nipecotic acid, Gabrene, baclofen and metatolylcarbamide (MTC), when given alone or in combination at subthreshold doses with AT II also at a subthreshold dose effective 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. Nipecotic acid (100 and 200 micrograms/mouse intracerebroventricularly [i.c.v.]) tended to decrease seizure intensity. Gabrene (25, 50, 100 and 250 mg/kg i.p.) inhibited PTZ-kindled seizures. Baclofen at a doses of 2.5 and 5 mg/kg i.p. tended to decrease seizure intensity and at a dose of 10 mg/kg was ineffective at all. MTC (50 and 75 mg/kg i.p.) tended to decrease and at a dose of 100 mg/kg significantly decreased seizure intensity. Combinations of subthreshold dose of AT II (0.05 micrograms/mouse i.c.v.) and subthreshold doses of nipecotic acid (100 micrograms/mouse) or Gabrene (10 mg/kg) or baclofen (10 mg/kg) or MTC (50 mg/kg) significantly decreased the intensity of PTZ-kindled seizures in mice. The observed potentiation of the anticonvulsive activity on PTZ-kindling suggests interactions of AT II receptors with GABA receptors (GABAA, GABAB or both), effected through allosteric mechanisms.
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; D001418:Baclofen / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007696:Kindling, Neurologic; D008297:Male; D051379:Mice; D009557:Nipecotic Acids / Q000494:pharmacology*; D010433:Pentylenetetrazole; D010671:Phenylurea Compounds / Q000494:pharmacology; D018079:Receptors, GABA / Q000187:drug effects*; D012640:Seizures; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000494:pharmacology
D009557:Nipecotic Acids; D010671:Phenylurea Compounds; D018079:Receptors, GABA; D000804:Angiotensin II; C017985:progabide; D005680:gamma-Aminobutyric Acid; C003616:3-tolylcarbamide; D001418:Baclofen; D010433:Pentylenetetrazole