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

• Published in: Clinics (São Paulo, Brazil) Vol. 79; p. 100435
• Main Authors: Zang, Dongdong, Yang, Xuemei, Wang, Hao, Li, Zhenxing, Ma, Yanjun, Liu, Jianxi, Mei, Xi, Li, Shupeng, Feng, Jinxing, Shi, Xin, Tan, Zhen
• Format: Journal Article
• Language: English; Portuguese
• Published: United States Elsevier España, S.L.U 01.01.2024; Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo; Faculdade de Medicina / USP
• Subjects: Antidepressant; Behavioral Sensitization Test; Conditioned Place Preference Test; Forced Swimming Test; Hydroxynorketamine and its Derivatives; MEDICINE, GENERAL & INTERNAL; Original; Antidepressant; Conditioned Place Preference Test; Forced Swimming Test; Behavioral Sensitization Test; Hydroxynorketamine and its Derivatives
• ISSN: 1807-5932; 1980-5322; 1980-5322
• DOI: 10.1016/j.clinsp.2024.100435

•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. 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.