Subtype selectivity of a new alpha(1)-adrenoceptor antagonist, JTH-601: Comparison with prazosin

The existence of alpha(1)-adrenoceptors with low affinity for prazosin (alpha(1L) group: alpha(1L) and alpha(1N) subtypes) has been proposed in addition to alpha(1)-adrenoceptor subtypes with high affinity for prazosin (alpha(1H) group: alpha(1A), alpha(1B) and alpha(1D) subtypes). A newly synthesized alpha(1)-adrenoceptor antagonist, JTH-601 (N-(3-hydroxy-6-methoxy-2,4,5-trimethylbenzyl)-N-methyl-2-(4- hydroxy-2-isopropyl-5-methyl-phenoxy) ethylamine hemifumarate) showed approximately a 10 times higher affinity for the alpha(1L) group, a similar affinity for the alpha(1A) subtype, but a more than 10 times lower affinity for the alpha(1B) and alpha(1D) subtypes when compared with prazosin. These results provide a further pharmacological evidence that alpha(1)-adrenoceptors with low affinity for prazosin exist in addition to those with high affinity for prazosin, suggesting that JTH-601 may be useful for characterising the alpha(1)-adrenoceptor subtypes.