Anticonvulsant and antilethal effects of imidazenil, a new imidazobenzodiazepine derivative, in fluostigmine (DFP; diisopropyl phosphorofluoridate) intoxications were studied and compared with the effects of diazepam on mice and rats. Special attention was payed to the myorelaxant effects of both drugs. It was stated that imidazenil (i) significantly decreased convulsion intensity in mice, (ii) quickly inhibited seizure patterns in bioelectrical activity in the rat's brain, (iii) significantly increased antilethal effectiveness of the standard therapy in mice intoxicated with DFP. These effects are comparable to those of diazepam. However, effects of imidazenil in the rota-rod test of the mouse were noted in doses 5-10 times higher than therapeutic ones, when effects of diazepam on motor co-ordination were seen in therapeutic dosage.
coupling of agonist binding to gating of the ion channel, indicating that agonist binding and subsequent ion channel opening are separate, but related processes. Phy differentially displaces [125 I]a-BGT from the chimeric nAChR, suggesting that the b subunit is not involved in Phy binding, and that Phy targets the insect agonist binding loop C.
ACKNOWLEDGEMENTSWe would like to thank Dr B Schmitt (Max-PlanckInstitut fu È r Hirnforschung, Frankfurt, Germany) and Dr M Ballivet (University of Geneva, Switzerland) for kindly providing us with cDNA encoding the SAD and the chick b2 subunit, respectively.
The therapeutic effectiveness of CGS 9896, a novel potent anxiolytic and anticonvulsant, in organophosphate intoxication was studied. It was demonstrated that this drug, used as an adjunct to a mixture of atropine and obidoxime, led to a rise in the LD50 of fluostigmine in mice of more than 150 times and more than 138 times for 2 and 24 h, respectively. After 24 h, this effect was twice that of diazepam, which served as a reference drug.
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