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  • Title: Anticonvulsant actions of fominoben: possible involvement of benzodiazepine receptors.
    Author: Baldino F, Krespan B, Geller HM.
    Journal: Pharmacol Biochem Behav; 1984 Jul; 21(1):137-43. PubMed ID: 6087374.
    Abstract:
    The purpose of this study was to examine the benzodiazepine-like activity of fominoben-HCl, a compound with prominent antitussive and respiratory stimulant actions. Towards this end we examined the anticonvulsant actions of fominoben as well as its ability to displace benzodiazepine (BDZ) binding from brain membranes. Scatchard analysis of binding data demonstrated that fominoben displaced 3H-flunitrazepam binding from rat cortical membrane preparations. Furthermore when tested against 3H-ethyl-beta-carboline-3-carboxylate, the addition of GABA resulted in a mean (+/- SE) shift of the IC50 from 4.05 +/- 0.10 microM to 2.2 +/- 0.05 microM, a characteristic of benzodiazepine agonists. Seizures were induced in male, Swiss Webster mice with pentylenetetrazol (PTZ) or 3-mercaptoproprionic acid (3-MP). Fominoben (50 and 100 mg/kg) completely protected mice from seizures induced by 50 mg/kg PTZ and elevated the seizure latency against 75 mg/kg of PTZ. The anticonvulsant effects of fominoben were less pronounced against 3-MP-induced seizures. The benzodiazepine antagonist Ro 15-1788 antagonized the anticonvulsant action of fominoben against both convulsants. Taken together, these data suggest that the anticonvulsant action of fominoben may be mediated by agonistic actions at benzodiazepine binding sites.
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