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.
Muramatsu
I
I
Department of Pharmacology, Fukui Medical School, Japan.
Takita
M
M
Suzuki
F
F
Miyamoto
S
S
Sakamoto
S
S
Ohmura
T
T
D000317:Adrenergic alpha-Antagonists / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003408:Cresols / Q000378:metabolism*; D006224:Cricetinae; D004285:Dogs; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011224:Prazosin / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000145:classification / Q000378:metabolism*; D013045:Species Specificity
D000317:Adrenergic alpha-Antagonists; D003408:Cresols; D011942:Receptors, Adrenergic, alpha; C101291:JTH 601; D011224:Prazosin