title: Is SDZ NVI-085 an alpha 1-adrenoceptor subtype-selective agonist?
abstract: 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.
authors.affiliation: Dept. Medicine, University of Essen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Büscher
authors.forename: P A
authors.initials: PA
authors.lastname: Insel
authors.forename: M C
authors.initials: MC
authors.lastname: Michel
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000378:metabolism / Q000494:pharmacology*; D001952:Bridged-Ring Compounds; D002417:Cattle; D002460:Cell Line; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D010078:Oxazines / Q000378:metabolism / Q000494:pharmacology*; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D014162:Transfection
chemical_list: D000316:Adrenergic alpha-Agonists; D001643:Bridged Bicyclo Compounds; D001952:Bridged-Ring Compounds; D007295:Inositol Phosphates; D010078:Oxazines; D011942:Receptors, Adrenergic, alpha; C074349:SDZ NVI-085; C051731:chlorethylclonidine; D003000:Clonidine; D009638:Norepinephrine; D011224:Prazosin