Pharmacological and biochemical evaluation of triethyltin's anticonvulsant effects.
Acute treatment of mice with triethyltin (TET) causes dose dependent anticonvulsant effects as determined by the maximal electroshock (MES) test: grade 1 (minimal) to grade 5 (maximal) seizures. Thirty minutes following 1 or 5 mg/kg TET mice exhibit 20% grade 4 and 80% grade 5 seizures or 90% grade 2 and 10% grade 3 seizures, respectively. These studies were designed to examine the neuropharmacological and neurochemical basis of this anticonvulsant effect. For MES testing, mice were injected with either reserpine, yohimbine, propranolol, haloperidol or metergoline prior to dosing with TET. Only reserpine and yohimbine blocked the previously noted anticonvulsant effects of TET. For chemical seizure testing, bicuculline ad picrotoxin were injected 30 minutes following TET. TET significantly decreased the convulsant effects of these GABAergic blockers. These results are interpreted to mean that TET preferentially interacts with the alpha-adrenergic and GABAergic transmitter systems to produce its anticonvulsant effects. In vitro receptor binding assays revealed no direct agonist activity of TET at either of these two sites. Possible alternative mechanisms are discussed.
D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001640:Bicuculline / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D010852:Picrotoxin / Q000633:toxicity; D011930:Reaction Time / Q000187:drug effects; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000187:drug effects; D011963:Receptors, GABA-A; D012110:Reserpine / Q000494:pharmacology; D014220:Trialkyltin Compounds / Q000494:pharmacology*; D014267:Triethyltin Compounds / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology
D000927:Anticonvulsants; D001640:Bicuculline; D010852:Picrotoxin; D011942:Receptors, Adrenergic, alpha; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D012110:Reserpine; D014220:Trialkyltin Compounds; D014267:Triethyltin Compounds; D015016:Yohimbine