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-hydro xy-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.