title: Further evidence for the interactions between angiotensin II and GABAergic transmission in pentylenetetrazol kindling seizures in mice.
abstract: 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.
authors.affiliation: Department of Experimental Pharmacology, Bulgarian Academy of Science, Sofia.
authors.forename: V P
authors.initials: VP
authors.lastname: Georgiev
authors.forename: M B
authors.initials: MB
authors.lastname: Lazarova
authors.forename: T S
authors.initials: TS
authors.lastname: Kambourova
mesh_terms: 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
chemical_list: 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