SB-269970 hydrochloride (SB-269970A) , a hydrochloride salt form of SB-269970, is a 5-HT7 receptor antagonist (pKi of 8.3) and exhibits >50-fold selectivity against other receptors.

SB-269970 inhibits 5-CT-stimulated adenylyl cyclase activity in guinea-pig hippocampal membranes. SB-269970 (0.03 μM, 0.1 μM, 0.3 μM and 1 μM) produces a concentration-related rightward-shift of the 5-CT concentration-response curve with no significant alteration in the maximal response to 5-CT. [1] SB-269970 (1 μM) has any effect on 5-HT efflux when superfused alone. [2]

SB-269970 (10 mg/kg and 30 mg/kg) significantly reduces the effects of amphetamine by 25 and 27%, respectively, and blocks the effects of ketamine by 38% (10 mg/kg) and 30% (30 mg/kg). SB-269970 significantly reduces amphetamine-induced hyperactivity in wild-type mice and is without effects in 5-HT7 knockout mice. Systemic administration of SB-269970 (30 mg/kg) significantly reverses amphetamine disruption of PPI and did not enhance PPI by itself compared to control. [3] SB-269970 significantly reverses the deficits induced by MK-801, but not by scopolamine. SB-269970 normalizes MK-801-induced glutamate but not dopamine release in the cortex. [4] SB-269970 (in one medium dose of 0.5 or 1 mg/kg) exerts a specific antianxiety-like effect in the Vogel drinking test in rats, in the elevated plus-maze test in rats and in the four-plate test in mice. Moreover, SB-269970 (in one medium dose of 5 or 10 mg/kg) reveals antidepressant-like activity in the forced swimming and the tail suspension tests in mice. [5] SB-269970 at doses of 0.3, 1 and 3 μg exhibits an anticonflict effect which is weaker than that of diazepam (40 μg), whereas SB-269970 at doses of 3 and 10 μg had marked anti-immobility action comparable to that of imipramine (0.1 μg). [6]