Nipradilol displays a unique pharmacological profile of affinities for the different alpha 1-adrenoceptor subtypes.
The selectivity of antagonistic effects of nipradilol, its four isomers and denitronipradilol, a major metabolite of nipradilol, on alpha 1-adrenoceptor subtypes in rat heart, brain and spleen were examined by radioligand binding assay with [3H]-prazosin. Pharmacological characteristics of these compounds were determined in isolated aortae from rats and guinea pigs. The order of the pKi values for alpha 1High-affinity sites in the heart, spleen and brain was SR > nipradiolol > or = RR > or = SS-RS >> denitronipradilol, but the order of the pKi values for the alpha 1Low-affinity sites was different in the heart and brain. There were good correlations between the pKi values of these compounds for the alpha 1High-affinity sites and the pA2 values for the contractile inhibition of the phenylephrine-induced response in rat aorta. There was no correlation between the pKi values of these compounds for the alpha 1Low-affinity sites and the pA2 values. These results indicate that: 1) alpha 1High-Affinity sites are related to vasoconstriction mediated by alpha 1-adrenoceptors; 2) Nipradilol and its isomers possess low affinity to alpha 1-adrenoceptors; and 3) The nitroxy group in nipradilol is important for its alpha 1-blocking activity.
Kinami
J
J
Department of Pharmacology, Niigata College of Pharmacy, Japan.
Tsuchihashi
H
H
Maruyama
K
K
Sasaki
K
K
Nagatomo
T
T
D000317:Adrenergic alpha-Antagonists / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D004983:Ethanolamines / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007536:Isomerism; D007741:Labetalol / Q000494:pharmacology; D008297:Male; D011224:Prazosin / Q000378:metabolism; D011412:Propanolamines / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism; D000096926:Benzenesulfonamides
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D007741:Labetalol; D011224:Prazosin; D011412:Propanolamines; D011942:Receptors, Adrenergic, alpha; C024523:arotinolol; C038539:3,4-dihydro-8-(2-hydroxy-3-isopropylaminopropoxy)-2H-1-benzopyran-3-ol; C032473:amosulalol; D000096926:Benzenesulfonamides; C036089:nipradilol