An effector analysis of the interaction of propoxazepam with antagonists of GABA and glycine receptors
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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.
Keywordspropoxazepam chemoconvulsants antiseizure action GABA antagonists
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- 2.Golovenko, N.Ya., Larionov, V.B., and Reder, A.S., Voloshchuk N.I., Valivodz I.P., Taran I.V, Zhurn. Natsional’noi Akademii Meditsinskikh Nauk Ukrainy, 2016, no. 3, pp. 251–260.Google Scholar
- 4.Pavlovskii, V.I., Kabanova, T.A., Khalimova, E.I., and Andronati, S.A., Vestnik Odesskogo Natsional’nogo Universiteta. Seriya “Khimiya”, 2013, vol. 18, no. 3, pp. 28–38.Google Scholar
- 5.Urbakh, V.Yu., in Statisticheskii analiz v biologicheskikh i meditsinskikh issledovaniyakh (Statistical Analysis in Medical Studies), Moscow: Meditsina, 1975.Google Scholar
- 6.Varden, B., in Matematicheskaya statistika (Mathematical Statistics), Moscow: Izd-vo Inostr. Lit, 1960.Google Scholar
- 10.Amakhin, D.V. and Veselkin, N.P., Tsitologiya, 2012, no. 6, pp. 469–477.Google Scholar
- 11.Danilov, A.B. and Davydov, O.S., in Neiropaticheskaya bol’ (Neuropathic Pain), Moscow: Borges, 2007.Google Scholar