(-)-Timolol is a more potent antagonist of the positive inotropic effects of (-)-adrenaline than of those of (-)-noradrenaline in human atrium

T. Wang, A. J. Kaumann, M. J. Brown

    Research output: Contribution to journalArticlepeer-review

    Abstract

    1. The affinity of (-)-timolol for β1- and β2-adrenoceptors was determined on isolated atrial preparations from patients undergoing open heart surgery. The times for onset and offset of antagonism of the positive inotropic effects of (-)-adrenaline and (-)-noradrenaline by (-)-timolol were measured. 2. The antagonism of the positive inotropic effects of (-)-adrenaline and (-)-noradrenaline by (-)-timolol (0.1-100 nM) was simple competitive in human atrium tissue. The slope of Schild-plots was not significantly different from 1.0 [0.93 ± 0.09 for (-)-adrenaline, 0.97 ± 0.09 for (-)-noradrenaline]. 3. The inotropic effects of(-)-adrenaline were antagonized significantly more by each concentration of (-)-timolol than those of (-)-noradrenaline. K(B)-values (-log M) were 10.10 ± 0.09 against (-)-adrenaline and 9.43 ± 0.07 against (-)-noradrenaline (P <0.001). 4. Blocking kinetics of (-)-timolol for the β-adrenoceptor were relatively slow. Half-times for the onset of blockade by 10 times K(B) of (-)-timolol were approximately 30 min for both (-)-adrenaline and (-)-noradrenaline; offset times were similar. 5. It is concluded that (-)-timolol has a higher affinity for the β2-adrenoceptor than for the β1-adrenoceptor in human atrium. This property may be beneficial clinically in protecting against the β2-adrenoceptor hypersensitivity induced by cardiac β1-adrenoceptor blockade, but also explain why severe asthma can occur after administration of very low intra-ocular doses of the drug.
    Original languageEnglish
    Pages (from-to)217-223
    Number of pages6
    JournalBritish Journal of Clinical Pharmacology
    Volume42
    Issue number2
    Publication statusPublished - 1996

    Keywords

    • β1- and β2 adrenoceptors
    • Adrenaline
    • Human atrium
    • Noradrenaline
    • Timolol

    Fingerprint

    Dive into the research topics of '(-)-Timolol is a more potent antagonist of the positive inotropic effects of (-)-adrenaline than of those of (-)-noradrenaline in human atrium'. Together they form a unique fingerprint.

    Cite this