ISSN:
1432-1912
Keywords:
α1-Adrenoceptor subtyes
;
Kidney
;
Alfuzosin
;
Naftopidil
;
Tamsulosin
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary We have used radioligand binding and inositol phosphate accumulation studies to determine the affinity at mixed α1A- and α1B-adrenoceptors (rat cerebral cortex and kidney), α1A-adrenoceptors (rat cerebral cortex and kidney following inactivation of α1B-adrenoceptors by chloroethylclonidine treatment) and α1B-adrenoceptors (rat spleen) for drugs currently under investigation for the treatment of benign prostatic hypertrophy, alfuzosin, naftopidil and (−)- and (+)-tamsulosin. Alfuzosin and naftopidil had similar affinities in all model systems (approximately 10 nM and 130 nM, respectively) and lacked relevant selectivity for α1-adrenoceptor subtypes. Their potency to inhibit noradrenaline-stimulated inositol phosphate formation in cerebral cortex matched their affinities as determined in the binding studies. Tamsulosin had higher affinity at α1A- than at α1B-adrenoceptors, and was slightly more potent than alfuzosin and naftopidil at α1B- and considerably more potent at α1A-adrenoceptors. However, the interaction of the tamsulosin isomers with chloroethylclonidine-insensitive (α1A-like) adrenoceptors was complex. A detailed analysis of the tamsulosin data and those obtained with other drugs, most notably noradrenaline and oxymetazoline, suggested that chloroethylclonidine-insensitive α1-adrenoceptors may be heterogenous and that this heterogeneity may differ between cerebral cortex and kidney of the rat.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00171338
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