5-HT2-Receptor Antagonists: a1- vs. 5-HT2-Receptor Blocking Properties in Blood Vessels: PDF Only5-HT2-Receptor Antagonists α1- vs. 5-HT2-Receptor Blocking Properties in Blood VesselsCohen, Marlene L.; Schenck, Kathyrn W.; Kurz, Ken D.Author Information Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, U.S.A. Address correspondence and reprint requests to Dr. M. L. Cohen at Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, U.S.A. Journal of Cardiovascular Pharmacology: Volume 11 - Issue - p S25-S29 Free Abstract LY53857, spiperone, ketanserin, and setoperone were potent and competitive 5-HT2-receptor antagonists in the rat jugular vein with equivalent affinities at 5-HT2 receptors. In the rat jugular vein, ritanserin blocked 5-HT2-mediated contractile responses with a depression of the maximum response in concentrations greater than 3 × 10−10M. Ketanserin, spiperone, ritanserin, and setoperone were also α1-adrenergic receptor antagonists, although affinity at α1-adrenergic receptors was less for ritanserin and setoperone than for ketanserin or spiperone. Of the 5-HT2-receptor antagonists examined, LY53857 was the most selective with respect to α1-adrenergic receptor affinity, showing 250,000-fold selectivity as an antagonist at 5-HT2 receptors. The possibility that the dual properties of 5-HT2- and α1-receptor blockade confer greater antihypertensive efficacy than α1-receptor blockade alone was also examined in vivo. However, acute administration of LY53857 at doses sufficient to abolish 5-HT2-receptor activation did not enhance blood pressure reduction produced by the α-adrenergic receptor antagonist phentolamine in normotensive or spontaneously hypertensive rats. These data argue against an important role for 5-HT2 receptors in blood pressure regulation even in combination with α-adrenergic receptor blockade. © Lippincott-Raven Publishers.