Alpha 2-agonist activity of the dopamine DA2-agonist LY171555

LY171555 is the active enantiomer of the racemate LY141865, a selective DA2-receptor agonist. LY171555 (10(-7)-10(-4) M) inhibited the twitch response to field stimulation in the adrenergically innervated rat vas deferens, a response due to activation of alpha 2-receptors as evidenced by total blockade with yohimbine (10(-6) M). The dopamine receptor antagonist sulpiride (10(-5) M) produced a small shift in the concentration-response curve to LY171555, consistent with the modest alpha 2-antagonist activity of sulpiride. LY171555 (10(-10)-10(-8) M) inhibited prolactin release from the anterior pituitary in vitro, a response due to activation of DA2-receptors as indicated by total blockade with sulpiride (10(-6) M). Thus, in addition to its predominant DA2-agonist activity, LY171555 can activate alpha 2-receptors in concentrations similar to those necessary for activation of histamine H2-receptors. Such concentrations were approximately 2,250-fold higher than necessary for DA2-receptor activation.