Study on the antidepressant activity of (2R,6R; 2S,6S)-Hydroxynorketamine (HNK) and its derivatives.
Dongdong Zang, Xuemei Yang, Hao Wang, Zhenxing Li, Yanjun Ma, Jianxi Liu, Xi Mei, Shupeng Li, Jinxing Feng, Xin Shi, Zhen Tan
Clinics (Sao Paulo, Brazil) January 1, 2024 DOI: 10.1016/j.clinsp.2024.100435 via PubMed
Summary
AI-generated from the abstractFour compounds derived from (2R,6R;2S,6S)-hydroxynorketamine (HNK) were tested for antidepressant effects in mice. In the forced swimming test, mice given 10 mg of HNK, compound I5, or compound I6 showed significantly less immobility time at 1 hour and 7 days compared to saline controls. Compounds C and D also reduced immobility in a glass cylinder test. In the locomotor sensitization test, compounds C and D increased movement distance on days 7 and 15 relative to day 1. Both compounds induced conditioned place preference, indicating rewarding effects. The results suggest compounds C and D may have some antidepressant activity, while HNK itself produced a rapid but short-lived antidepressant effect within one week.
Study at a glance
| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | (2R 6R; 2S 6S)-HNK compound C compound D |
| Dose | 10 mg |
| Duration | 7 days |
| Keywords | Behavioral sensitization test Forced swimming test Antidepressants antidepressant medication Depression medication Mood medication |
| Citations | 4 |
| Key finding | Compounds C and D derived from HNK may have antidepressant activity, while HNK itself produces a rapid but short-lived antidepressant effect within one week. |
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.