Protective Effect of R(—)-1-(Benzo[b]thiophen-5-yl)-2-[2-(A£A-diethylamino)ethoxy]ethanol Hydrochloride (T-588), a Novel Cerebral Activator, against Experimental Cerebral Anoxia

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Abstract
α1-Adrenoceptors in the rat prostate were characterized by a binding assay using the newly synthesized radioligand [3H]-YM617 (5-[2-[[2[ethoxyring(n)-3H](o-ethoxyphenoxy)ethyl]amino] propyl]-2-methoxybenzenesulfonamide HCl) and an in vitro assay. Specific [3H]-YM617 binding in the rat prostate was saturable and of high affinity (KD = 61.5±5.9 pM) with 23.2±6.9 fmol/mg of protein as the maximal number of binding sites (Bmax). α-Adrenoceptor agonists and antagonists inhibited the binding of the radioligand with the following order of effectiveness: YM617 > prazosin = bunazosin > WB4101 >5-methyl-urapidil = phenoxybenzamine > phentolamine > S(+)-isomer of YM617 > yohimbine > norepinephrine > phenylephrine>methoxamine. α1-Adrenoceptors in the rat prostate preferred the R(-)-isomer of YM617 to the S(+)-isomer. Preincubation with chlorethylclonidine (CEC; 10-5M, 10 min) just slightly changed the Bmax value for [3H]-YM617 without changing the KD value in the prostate; however, CEC reduced the Bmax in the aorta. In the isolated tissue, pretreatment with CEC (10-5M, 10 and 30 min) time-dependently shifted to the right the dose-response curve for phenylephrine and decreased the maximal contraction of aortas induced by phenylephrine, but did not shift or decrease those of prostates. The present results indicate that the α1-adrenoceptors in the rat prostate are mainly CEC-insensitive (α1A), whereas those in the aorta are CEC-sensitive (α1B).