IS SDZ NVI-085 AN ALPHA(1)-ADRENOCEPTOR SUBTYPE-SELECTIVE AGONIST

SDZ NVI-085 has been proposed to be a centrally acting agonist with selectivity for some alpha(1)-adrenoceptor subtypes. We have investigated its selectivity and efficacy at alpha(1)-adrenoceptor subtypes in rat tissues and at cloned subtypes. SDZ NVI-085 had higher affinity for chloro-ethylclonidine-insensitive (alpha(1A)-like) than for -sensitive (alpha(1B)) (alpha(1)-adrenoceptors in rat kidney but not in cerebral cortex. SDZ NVI-085 recognized cloned alpha(1)-adrenoceptor subtypes expressed in COS cells with the order of potency bovine alpha(1C) > rat alpha(1A/D) > rat alpha(1B). Relative to 100 mu M noradrenaline, SDZ NVI-085 was only a partial agonist for stimulation of inositol phosphate formation in rat kidney and inhibited noradrenaline-stimulated inositol phosphate formation in native and chloroethylclonidine-treated tissue. We conclude that SDZ NVI-085 discriminates among multiple alpha(1)-adrenoceptor subtypes and is a partial agonist at rat renal alpha(1A)- and alpha(1B)-adrenoceptors.