Effect of the chromone-containing derivative allylmorpholine on behavior and temperature of small laboratory animals under stress conditions

Introduction. Chromone-containing allylmorpholine derivatives (PAMs) are a new group of biologically active compounds with putative psychotropic activity. In a series of experiments on Danio rerio, PAMs demonstrated a pronounced dose-dependent sedative effect, and compound 33a at low doses exerted anxiolytic effects in the Novel tank test. Screening by pharmacoencephalography of another molecule from the PAM series, 33b, demonstrated similarity of its effects on EEG with the dopamine blocker sulpiride and the antihistamine agent chloropyramine. Based on the results of this prediction, the molecule can be hypothesized to have sedative and antipsychotic effects.

Aim. To study the pharmacological activity of compound 33b in tests for exploratory and anxiety behavior in mice, as well as in the test "Stress-induced hyperthermia" in rats.

Materials and methods. The pharmacological activity of 33b was evaluated in the Open Field (OF), Elevated Plus Maze (EPM), Light-Dark Box test (LDB) tests in male and female mice, as well as in the Stress-Induced Hyperthermia test in male Wistar rats.

Results and discussion. In the OF, EPM and LDB tests, the studied compound 33b at doses of 50 and 80 mg/kg resulted in a persistent decrease in the number of stance in both females and males. The decrease in locomotor activity in the OF test remained at trend level without statistical significance. Suppression of vertical activity in males occurred when lower doses of 33b were administered than in females. No data on the anxiolytic action of the molecule in these tests were obtained. In the test "Stress-induced hyperthermia" a pronounced decrease in body temperature was observed in rats when 33b was administered at a dose of 60 mg/kg.

Conclusion. The data obtained demonstrated a moderate sedative effect of compound 33b, while the sensitivity of males to the action of the molecule was higher. In the test on rats for the studied PAM was shown hypothermic action under stress conditions, which may be a confirmation of its dopamine-blocking action. This allows us to consider substance 33b from the group of chromone-containing allylmorpholines as a promising compound for further studies as a potential antipsychotic agent.

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