A pharmacological profile of propoxazepam — a new antiepileptic substance
DOI:
https://doi.org/10.15407/dopovidi2018.12.098Keywords:
chemical and electrical convulsants, propoxazepam, safety factor, therapeutic index, therapeutic interval, therapeutic widenessAbstract
The analysis of the dose-effect pharmacological action for propoxazepam on the models of chemically and electrically induced seizures is carried out. The peculiarities of the compound influence on the different genesis seizures manifestations and their redistribution are determined. Pharmacological indices (therapeutic index, wideness, interval, and safety factor) have been calculated, which characterize the efficacy and safety of propoxazepam. The data presented suggest that the future use of propoxazepam as an antiepileptic agent is more secure in those pathologies that are more relevant to the GABA- and glycine-ergic mechanisms.
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Sauro, K. M., Wiebe, S., Dunkley, C., Janszky, J., Kumlien, E., Moshé, S., Nakasato, N., Pedley, T. A., Perucca, E., Senties, H., Thomas, S. V., Wang, Y., Wilmshurst, J. & Jetté, N. (2016). The current state of epilepsy guidelines: A systematic review. Epilepsia, 57, No. 1, pp. 13-23. doi: https://doi.org/10.1111/epi.13273
Löscher, W. & Schmidt, D. (1988). Which animal models should be used in the search for new antiepileptic drugs? A proposal based on experimental and clinical considerations. Epilepsy Res., 2, No. 3, pp. 145-181. doi: https://doi.org/10.1016/0920-1211(88)90054-X
Deshmukh, R., Thakur, A. S. & Dewanga, D. (2011). Mechanism of action of anticonvulsant drugs: a review. Int. J. Pharm. Sci. Res., 2, No. 2, pp. 225-236.
Pavlovsky, V. I., Tsymbalyuk, O. V., Martynyuk, V. S., Kabanova, T. A., Semenishyna, E. A., Khalimova, E. I. & Andronati, S. A. (2013). Analgesic effects of 3-substituted derivatives of 1,4-benzodiazepines and their possible mechanisms. Neurophysiology, 45, No. 5/6, pp. 427-432. doi: https://doi.org/10.1007/s11062-013-9389-y
Sills G.J. (2006). The mechanisms of action of gabapentin and pregabalin. Curr. Opin. Pharmacol., 6, No. 1, pp. 108-113. doi: https://doi.org/10.1016/j.coph.2005.11.003
Golovenko, N. Ya., Larionov, V. B., Andronati, S. A., Valivodz', I. P. & Yurpalova, T. A. (2018). Rharmacodynamic analysis of propoxazepam interaction with GABA-benzodiazepine-receptor-ionophore complex. Neuro phy siology, 50, No. 1, pp. 2-10. doi: https://doi.org/10.1007/s11062-018-9711-9
Golovenko, N. Ya., Larionov, V. B., Reder, A. S. & Valivodz', I. P. (2017). An effector analysis of the interaction of propoxazepam with antagonists of GABA and glycine receptors. Neurochem. J., 11, No. 4, pp. 302-308. doi: https://doi.org/10.1134/S1819712417040043
Golovenko, M. Ya., Reder, A. S., Larionov, V. B. & Balivodz', I. P. (2017). Propoxazepam influence on thiosemicarbazide-induced GABA-deficient seizures development in mice. Clin. Pharm., 21, No. 2, pp. 34-40.
Urbakh, V. Yu. (1975). Statistical analysis in medical studies. Moscow: Meditsina (in Russian).
Varden, B. (1960). Mathematical Statistics. Moscow: Izd-vo Inostr. Lit. (in Russian).
Cramer, C. L., Stagnitto, M. L., Knowles, M. A. & Palmer, G. C. (1994). Kainic acid and 4-aminopyridine seizure models in mice: evaluation of efficacy of anti-epileptic agents and calcium antagonists. Life Sci., 54, No. 16, pp. 271-275. doi: https://doi.org/10.1016/0024-3205(94)00845-0
Koella, W. P. (1985). Animal experimental methods in the study of antiepileptic drugs. In.: Antiepileptic drugs (pp. 283-340). Berlin, Heidelberg: Springer. doi: https://doi.org/10.1007/978-3-642-69518-6_12
Bloom, P., Madeja, M., Mushhoff, U., & Specmann, E.-J. (1996). Effects of pentylenetetrazole on GABA receptors expressed in oocytes of Xenopus laervus: extra- and intracellular sites of action. Neurosci. Let., 205, pp. 115-118. doi: https://doi.org/10.1016/0304-3940(96)12391-0
Clayton, T., Chen, J. L., Ernst, M., Richter, L., Cromer, B. A., Morton, C. J., Ng, H., Kaczorowski, C. C., Helmstetter, F. J., Furtmüller, R., Ecker, G., Parker, M. W., Sieghart, W. & Cook, J. M. (2007).An updated unified pharmacophore model of the benzodiazepine binding site on γ-aminobutyric acida receptors: correlation with comparative models. Curr. Med. Chem., 14, pp. 2755-2775. doi: https://doi.org/10.2174/092986707782360097
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