In vitro receptor specificity of the 5HT1A selective phenylpiperazine, LY165163.
LY165163, a ligand reported to be selective for the 5HT1A subtype of serotonin receptor, was examined for its ability to interact with 5HT2 receptors in the rat jugular vein and alpha-receptors in the rat aorta. In these smooth muscle preparations, no agonist activity of LY165163 occurred in concentrations up to 10(-5) M. However, LY165163 was an antagonist of serotonin-induced contractions in the jugular vein and of norepinephrine-induced contractions in the rat aorta. The dissociation constant calculated for LY165163 at 5HT2 receptors in the rat jugular vein was 10(-8) M and at alpha-receptors in the rat aorta was 2 X 10(-7) M. Thus, LY165163 is a relatively potent antagonist at vascular 5HT2 sites and possesses appreciable affinity at alpha-receptors. Based on these data, the multiple receptor interactions of LY165163 must be taken into consideration when utilizing this agent as a probe for the 5HT1A subtype of serotonin receptor.
D000317:Adrenergic alpha-Antagonists; D000818:Animals; D001681:Biological Assay; D002540:Cerebral Cortex / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D010879:Piperazines / Q000378:metabolism*; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000145:classification / Q000378:metabolism*; D012701:Serotonin / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D011942:Receptors, Adrenergic, alpha; D011985:Receptors, Serotonin; D012701:Serotonin; C044643:LY 165163