(-)-Stepholidine

(-)-Stepholidine is a dopamine receptor antagonist and a partial agonist of the serotonin (5-HT) receptor subtype 5-HT1A.{45111,45112,45113} (-)-Stepholidine binds to dopamine D1, D2, D3, D4, and D5 receptors (Kis = 5.1, 11.6, 24, 1,450, and 5.8 nM, respectively) as well as 5-HT1A, 5-HT2B, a2C-adrenergic receptors (a2C-ARs), and sigma-2 (?2) receptors in a radioligand binding assay (Kis = 143, 226, 215, and 53 nM, respectively).{45111} It inhibits dopamine-induced cAMP accumulation in HEK293 cells expressing dopamine D1, D2, and D5 receptors with IC50 values of 20.5, 128, and 27 nM, respectively. (-)-Stepholidine inhibits forskolin-induced cAMP production in CHO cells expressing rat 5-HT1A receptors (EC50 = 1.2 ?M).{45112} In vivo, (-)-stepholidine (1 mg/kg, i.v.) increases dopamine neuron firing rates, the number of spikes in bursts, and the amplitude of slow oscillations by 20, 155, and 126%, respectively, in the rat ventral tegmental area (VTA), effects that can be blocked by the 5-HT1A antagonist WAY-100635 (Item No. 14599).{45113} Pretreatment with (-)-stepholidine inhibits amphetamine- and phencyclidine-induced locomotor activity in rats (ED50s = 2.4 and 6.5 mg/kg, respectively).{45114}