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 microM 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.