Affinity of serotonin receptor antagonists and agonists to recombinant andnative alpha(1)-adrenoceptor subtypes

Binding affinities of serotonin (5-HT)-receptor antagonists and agonists at human recombinant alpha (1)-adrenoceptor subtypes (alpha (1a)-, alpha (1b) - and alpha (1d)-subtypes) were examined and compared with the functional a ffinities obtained in rat caudal artery (alpha (1A)-subtype), dog carotid a rtery (alpha (1B)-subtype) and rat thoracic aorta (alpha (1D)-subtype). Mos t of the 5-HT-receptor antagonists and agonists tested showed relatively hi gh affinity to three alpha (1)-adrenoceptor subtypes. The highest affinity close to 1 nM was seen for NAN-190 (5-HT1A antagonist) in binding and funct ional studies. 5-Methylurapidil (5-HT1A agonist) and BMY7378 (5-HT1A agonis t) showed, respectively, alpha (1a)(alpha (1A))- or alpha (1d)(alpha (1D))- subtype selectivity in both binding and functional affinities, but spiperon e (5-HT2A antagonist) showed alpha (1b)-selectivity only in binding affinit y. Functional affinity of ritanserin (5-HT2A antagonist) to the alpha (1B)- subtype was approximately 500-fold lower than that of affinity to the alpha (1b)-subtype. The present results show that many 5-HT-receptor antagonists and agonists have high affinity to alpha (1)-adrenoceptors, but suggest th at there is deviation between their functional affinities and binding affin ities for some drugs.