The effect of propoxazepam on development of thiosemicarbazide-induced GABA-deficient seizures in mice
Keywords:propoxazepam, thiosemicarbazide, convulsions, GABA-deficiency
Aim. To study the mechanisms of action for propoxazepam, a new compound with the analgesic action, on the model of thiosemicarbazide-induced GABA-deficient seizures.
Matherials and methods. A chemoconvulsive agent was injected subcutaneously (20 mg/kg) 0.5 hours after intraperitoneal introduction of propoxazepam. The number and the time of appearance of different types of convulsions, as well as the relative number of survived animals (for ED50 calculation) were registered.
Results. The first seizure manifestations in animals began to appear at the first minute after thiosemicarbazide introduction (control), while introduction of propoxazepam already in the dose of 0.01 mg/kg increased this time up to 70 min. Against the background of propoxazepam introduction (0.1 mg/kg) there was an increase in the animals’ life duration up to 128 ± 16 min, with the doses above 0.3 mg/kg the survival was longer than 3-hour period of observation. The increase of the propoxazepam dose led to redistribution between the clonic and tonic convulsions. In the experimental groups there was a decrease in the time of occurrence of myoclonic convulsions and an increase in their number along with a reduction in the number of tonic convulsions. It indicates the increase in efficiency of inhibitory processes in the CNS.
Conclusions. The mean effective dose of propoxazepam as a protective effect on the model of thiosemicarbazide-induced seizures is 0.18 ± 0.10 mg/kg (0.31 ± 0.05 mmol/kg) with the “dose–effect” curve slope of 0.6 corresponding to the rapid development of the protective effect and antagonistic interactions at the receptor level.
Danilov, A. B., Davydov, O. S. (2007). Neiropaticheskaia bol.Moscow: Borges, 2007. – 198.
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 (5–6), 427–432. doi: 10.1007/s11062–013–9389–y
Blommel, M. L., Blommel, A. L. (2007). Pregabalin: An antiepileptic agent useful for neuropathic pain. American Journal of Health–System Pharmacy, 64 (14), 1475–1482. doi: 10.2146/ajhp060371
Taylor, C. P., Gee, N. S., Su, T.–Z., Kocsis, J. D., Welty, D. F., Brown, J. P., Singh, L. (1998). A summary of mechanistic hypotheses of gabapentin pharmacology. Epilepsy Research, 29 (3), 233–249. doi: 10.1016/s0920–1211(97)00084–3
Golovenko, N. Ya., Golovenko, V. B., Reder, A. S. et al. (2016). Zhurnal Natcionalnoi akademii meditcinskikh nauk Ukrainy, 3, 247–252.
Roa, P. D., Tews, J. K., Stone, W. E. (1964). A neurochemical study of thiosemicarbazide seizures and their inhibition by amino–oxyacetic acid. Biochemical Pharmacology, 13 (3), 477–487. doi: 10.1016/0006–2952(64)90168–6
Urbakh, V. Yu. (1975). Statisticheskii analiz v biologicheskikh i meditcinskikh issledovaniiakh.Moscow: Meditcina, 297.
Panosyan, E. H., Lin, H. J., Koster, J., Lasky, J. L. (2017). In search of druggable targets for GBM amino acid metabolism. BMC Cancer, 17 (1). doi: 10.1186/s12885–017–3148–1
Ben–Menachem, E. (2011). Mechanism of action of vigabatrin: correcting misperceptions. Acta Neurologica Scandinavica, 124, 5–15. doi: 10.1111/j.1600–0404.2011.01596.x
Holovenko, M. Ya., Larionov, V. B., Reder, A. S. et al. (2017). Odeskyi medichnyi zhurnal, 6, 9–15.
Copyright (c) 2017 National University of Pharmacy
This work is licensed under a Creative Commons Attribution 4.0 International License.Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).