In:
British Journal of Pharmacology, Wiley, Vol. 133, No. 8 ( 2001-08), p. 1330-1338
Abstract:
The present study investigated whether or not there may be differences in the direct cardiac actions of the novel, highly β 1 ‐selective adrenoceptor antagonist nebivolol (NEB) in comparison to metoprolol (MET), bisoprolol (BIS), carvedilol (CAR) and bucindolol (BUC) in human myocardium ( n =9). The rank order of β 1 ‐selectivity as judged by competition experiments to 3 H‐CGP 12.1777 in the presence of CGP 207.12 A (300 nmol l −1 , K i β 2 ) or ICI 118.551 (50 nmol l −1 , K i β 1 ) were NEB( K i β 2 / K i β 1 : 40.7) 〉 BIS(15.6) 〉 MET(4.23) 〉 CAR(0.73) 〉 BUC(0.49). The rank order of the negative inotropic potency of the β ‐adrenoceptor antagonists measured in left ventricular trabeculae (dilated cardiomyopathy, DCM) as judged by the concentration needed to induce a 50% decrease in isoprenaline (1 μmol l −1 )‐stimulated force (IC 50 ) was: MET (0.6 μmol l −1 ) 〉 CAR (4.1 μmol l −1 ) 〉 NEB (7.0 μmol l −1 ). NEB, BUC, MET and CAR did not not exert an intrinsic sympathomimetic activity (ISA) as determined by measurements of force development in forskolin (0.3 μmol l −1 ) pre‐treated left ventricular trabeculae, nor by measuring adenylate cyclase activity in forskolin (0.3 μmol l −1 )‐stimulated assays (crude membranes). This also holds true for radioligand binding assays with or without guanine nucleotide guanyl‐5′‐yl imidodiphosphate (Gpp(NH)p). Although all studied β ‐adrenoceptor antagonists lack intrinsic sympathomimetic activity (ISA), they differ in the β 1 ‐selectivity as well as in their direct negative inotropic action. These differences as well as the mode of extracardiac action may have an impact on outcome of patients treated with β ‐adrenoceptor antagonists. British Journal of Pharmacology (2001) 133 , 1330–1338; doi: 10.1038/sj.bjp.0704188
Type of Medium:
Online Resource
ISSN:
0007-1188
,
1476-5381
DOI:
10.1038/sj.bjp.0704188
Language:
English
Publisher:
Wiley
Publication Date:
2001
detail.hit.zdb_id:
2029728-2
SSG:
15,3
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