| Autor: |
Maack, C., Tyroller, S., Schnabel, P., Cremers, B., Dabew, E., Südkamp, M., Maack, C. |
| Zdroj: |
British Journal of Pharmacology; April 2001, Vol. 132 Issue: 8 p1817-1826, 10p |
| Abstrakt: |
1 Intrinsic activity and β1-selectivity are important features of β-blockers in the treatment of patients with coronary syndromes and heart failure. In human myocardium, intrinsic activity and β1-selectivity of the novel β-adrenoceptor antagonist nebivolol have not yet been determined. 2 The study examines intrinsic activity, β-adrenoceptor-G-protein coupling and β1-selectivity of nebivolol and bisoprolol in human ventricular myocardium. Furthermore, intrinsic activity of both compounds is compared to the one of bucindolol, carvedilol and metoprolol in human atrial myocardium. 3 Radioligand binding studies ([125I]-lodocyanopindolol) were performed on membrane preparations of human failing and nonfailing myocardium and on COS-7 cells transfected with human β1- and β2-adrenoceptors, respectively. Functional experiments were carried out on isolated muscle preparations of human left ventricular and right atrial myocardium from failing and nonfailing hearts. 4 Radioligand binding studies reveal 3 – 4 fold β1-selectivity for nebivolol and 16 – 20 fold β1-selectivity for bisoprolol in human myocardium. In COS-7-cells, β1-selectivity is 3 fold for nebivolol and 15 fold for bisoprolol. 5 Neither the binding of nebivolol nor of bisoprolol is affected by the presence of guanylylimidodiphosphate (Gpp(NH)p). 6 Nebivolol and bisoprolol exert similar inverse agonist activity in human ventricular as well as atrial myocardium. In atrial myocardium, inverse agonism of both compounds is higher compared to bucindolol, equal to carvedilol and lower compared to metoprolol. 7 Favourable haemodynamic effects of nebivolol in humans are not due to β1-selectivity or partial agonist activity of this agent. Other mechanisms, i.e. the production of nitric oxide, may thus be responsible for its unique haemodynamic profile. British Journal of Pharmacology (2001) 132, 1817 – 1826 |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
Plný text