Abstract The 5-HT 7 receptor (5-HT 7 R) is a promising therapeutic target for the treatment of depression and neuropathic pain. The 5-HT 7 R antagonist SB-269970 exhibited antidepressant-like activity, whereas systemic administration of the 5-HT 7 R agonist AS-19 significantly inhibited mechanical hypersensitivity and thermal hyperalgesia. In our efforts to discover selective 5-HT 7 R antagonists or agonists, aryl biphenyl-3-ylmethylpiperazines ...