Jpn. J. Pharmacol. 86 (2), 189-195 (2001)

Affinity of Serotonin Receptor Antagonists and Agonists to Recombinant and Native a1-Adrenoceptor Subtypes

Rika Yoshio1,2, Takanobu Taniguchi1, Harumi Itoh2 and Ikunobu Muramatsu1,*

Departments of 1Pharmacology and 2Radiology, School of Medicine, Fukui Medical University, Matsuoka, Fukui 910-1193, Japan

*Corresponding author. FAX: +81-776-61-8130, E-mail:

Abstract: Binding affinities of serotonin (5-HT)-receptor antagonists and agonists at human recombinant a1-adrenoceptor subtypes (a1a-, a1b- and a1d-subtypes) were examined and compared with the functional affinities obtained in rat caudal artery (a1A-subtype), dog carotid artery (a1B-subtype) and rat thoracic aorta (a1D-subtype). Most of the 5-HT-receptor antagonists and agonists tested showed relatively high affinity to three a1-adrenoceptor subtypes. The highest affinity close to 1 nM was seen for NAN-190 (5-HT1A antagonist) in binding and functional studies. 5-Methylurapidil (5-HT1A agonist) and BMY7378 (5-HT1A agonist) showed, respectively, a1a(a1A)- or a1d(a1D)-subtype selectivity in both binding and functional affinities, but spiperone (5-HT2A antagonist) showed a1b-selectivity only in binding affinity. Functional affinity of ritanserin (5-HT2A antagonist) to the a1B-subtype was approximately 500-fold lower than that of affinity to the a1b-subtype. The present results show that many 5-HT-receptor antagonists and agonists have high affinity to a1-adrenoceptors, but suggest that there is deviation between their functional affinities and binding affinities for some drugs.

Keywords: Serotonin receptor antagonist, Serotonin receptor agonist, a1-Adrenoceptor, Selectivity
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