An effector analysis of the interaction of propoxazepam with antagonists of GABA and glycine receptors

详细

Using effector analysis, we studied the mechanism of anti-seizure activity of the alcoxy-derived benzodiazepine (propoxazepam). In models of chemically induced seizures we determined the average molar and weight effective doses (ED₅₀) of propoxazepam as an antagonist of picrotoxin (4.10 ± 0.21 μmol/kg, 1.67 ± 0.09 mg/kg), pentylenetetrazole (2.24 ± 0.93 μmol/kg, 0.9 ± 0.04 mg/kg), and strychnine (40.33 ± 14.91 μmol/kg, 14.24 ± 0.47 mg/kg), which reflect the high activity level of the substance. On the basis of dose–effect curves, using comparative quantile analysis for chemoconvulsants with different mechanisms of action, we showed different stages of interaction of propoxazepam with GABA and glycine receptors under in vivo conditions. We evaluated the partial contribution of myoclonic and toxic components to the general structure of seizures induced by various chemoconvulsants. We believe that the results we obtained indicate that the anti-seizure action of propoxazepam is predominantly mediated by a GABAergic mechanism. Glycinergic components of the inhibition of strychnine-induced seizures by propoxazepam occur at doses that exceed the ED₅₀ and seem to be an additional means of anti-seizure action.