Volume 14, Issue 33, January - June, 2020

Sedative-hypnotic and muscle relaxant activities of propoxazepam in animal models and investigation on possible mechanisms

Mykola Golovenko, Vitalii Larionov^♦, Anatoliy Reder, Iryna Valivodz, Zhanna Tsapenko

A.V. Bogatsky Physico-Chemical Institute of the National Academy of Sciences of Ukraine, Odessa, Ukraine

^♦Corresponding author
Vitalii Larionov, 65080, Lyustdorfskaya Road, 86, Odessa, e-mail: vitaliy.larionov@gmail.com

ABSTRACT

Introduction: Analgesic (for both neuropathic and nociceptive pain) and anticonvulsant action of 7-bromo-5-(o-chlorophenyl)-3- propoxy-1,2-dihydro-3H-1,4-benzodiazepin-2-one (propoxazepam) make it perspective for further studying. Objectives: Propoxazepam was evaluated for sedative-hypnotic-like activity in mice and involved mechanisms in a battery of tests: acute oral toxicity, motor coordination and muscle relaxation studies. Materials and Methods: Acute toxicity (rats) and thiopental-induced sleeping (mice) were determined as motor coordination and muscle relaxation. Results: As relatively nontoxic substance (LD50>5000 mg/kg) propoxazepam belong to fifth category according to GHS toxicity classification. At high doses (700, 1100 and 1300 mg/kg, i.p.) a delay in the righting reflex was observed but not a total loss. The results indicated that substance induces hypnotic effects. Because propoxazepam produces any effect on rotarod test, seems that its effects on sleeping time and sleep latency are mediated by affecting motor movement. Conclusion: Based on previous results and present data, it should be presumed that GABAergic mechanisms may be involved in the potentiating effect of propoxazepam on thiopental-induced sleeping time and sleep latency in mice. Propoxazepam potentiates sleep induced by hypnotics like thiopental, but can not induce hypnosis by itself

Keywords: propoxazepam; acute oral toxicity; hypnotic; motor coordination; muscle relaxation

Drug Discovery, 2020, 14(33), 155-162

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