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.) injec...

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Bibliographic Details
Published in:Neuropeptides (Edinburgh) 1995, Vol.28 (1), p.29-34
Main Authors: Georgiev, V.P, Lazarova, M.B, Kambourova, T.S
Format: Article
Language:English
Subjects:
Angiotensin II - pharmacology
Animals
Anticonvulsants. Antiepileptics. Antiparkinson agents
Baclofen - pharmacology
Biological and medical sciences
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Interactions
gamma-Aminobutyric Acid - analogs & derivatives
gamma-Aminobutyric Acid - pharmacology
Kindling, Neurologic
Male
Medical sciences
Mice
Neuropharmacology
Nipecotic Acids - pharmacology
Pentylenetetrazole
Pharmacology. Drug treatments
Phenylurea Compounds - pharmacology
Receptors, GABA - drug effects
Seizures
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Summary: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 μg/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 μg/mouse i.c.v.) and subthreshold doses of nipecotic acid (100 μg/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 (GABA A, GABA B or both), effected through allosteric mechanisms.
ISSN:0143-4179
1532-2785
DOI:10.1016/0143-4179(95)90071-3