The effect of propoxazepam on development of thiosemicarbazide-induced GABA-deficient seizures in mice

Authors

  • M. Ya. Golovenko A. V. Bogatskiy Physical-Chemical Institute of the NAS of Ukraine, Ukraine
  • A. S. Reder A. V. Bogatskiy Physical-Chemical Institute of the NAS of Ukraine, Ukraine
  • V. B. Larionov A. V. Bogatskiy Physical-Chemical Institute of the NAS of Ukraine, Ukraine
  • I. P. Valivodz` A. V. Bogatskiy Physical-Chemical Institute of the NAS of Ukraine, Ukraine

DOI:

https://doi.org/10.24959/cphj.17.1419

Keywords:

propoxazepam, thiosemicarbazide, convulsions, GABA-deficiency

Abstract

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.

Author Biographies

M. Ya. Golovenko, A. V. Bogatskiy Physical-Chemical Institute of the NAS of Ukraine

academician of NAMS of Ukraine, doctor of sciences in biology, professor, Head of Department of A. V. Bogatskiy
Physical-Chemical Pharmacology

A. S. Reder, A. V. Bogatskiy Physical-Chemical Institute of the NAS of Ukraine

PhD in chemistry, Senior Researcher

V. B. Larionov, A. V. Bogatskiy Physical-Chemical Institute of the NAS of Ukraine

doctor of sciences in biology, Senior Researcher of Department of Physical-Chemical Pharmacology

I. P. Valivodz`, A. V. Bogatskiy Physical-Chemical Institute of the NAS of Ukraine

PhD student of A.V. Bogatskiy Physical-Chemical Institute of NAS of Ukraine

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Published

2017-06-14

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Section

Pre-clinical studies of new drugs