Study on the antidepressant activity of (2R,6R; 2S,6S)-Hydroxynorketamine (HNK) and its derivatives.

Summary

A promising breakthrough in rapid-acting antidepressants shows that Hydroxynorketamine and its derivatives can lift depression symptoms within hours. Through behavioral tests including forced swimming and place preference tests, researchers found two compounds that significantly reduced depressive behaviors in mice. While the effects were powerful and quick-acting, they lasted about a week, offering hope for new fast-acting depression treatments.

Abstract

This study mainly explores (2R,6R; 2S,6S)-HNK and its compounds whether there are antidepressant effects. Four HNK compounds were obtained from 2-(Chlorophenyl) Cyclopentylmethanone. Forced swimming test, locomotor sensitization test, and conditioned location preference test were used to screen the antidepressant activity of the synthesized target compounds. In the case of 10 mg HNK treatment, compared with saline, the immobile time of mice in the HNK group, I5 group and I6 group at 1 h and 7 days had statistical significance. In the case of 10 mg HNK treatment, compared with saline, the immobile time of compound C and D groups in the glass cylinder area was significantly different. In the locomotor sensitization test, the movement distance of compound C and D groups on day 15 and day 7 mice increased significantly compared with the first day. In the conditioned place preference experiment, compound C and compound D induced conditioned place preference in mice compared with the Veh group. The results of the forced swimming test, locomotor sensitization test, and conditioned location preference test showed that compounds C and D may have certain anti-depressant activity. However, HNK exerts a rapid and significant antidepressant effect within 1 week, but the duration is short.

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