In:
British Journal of Clinical Pharmacology, Wiley, Vol. 47, No. 1 ( 1999-01), p. 59-66
Abstract:
Aims To study whether desensitization occurs after long‐term administration of the β 1 ‐adrenoceptor partial agonist xamoterol and, if so, whether this can be influenced by ketotifen. Methods In a double‐blind, randomized design 10 young, healthy males received ketotifen (2×1 mg day −1 p.o.) or placebo for 3 weeks with xamoterol (2×200 mg day −1 p.o.) administered concomitantly during the last 2 weeks. β 1 ‐adrenoceptor mediated responses were assessed as exercise‐induced tachycardia and isoprenaline‐induced shortening of heart rate corrected electromechanical systole (QS 2 c); isoprenaline‐induced tachycardia was measured as a mixed β 1 ‐/β 2 ‐adrenoceptor‐mediated effect. Results The first dose of xamoterol significantly increased resting heart rate and systolic blood pressure and significantly shortened QS 2 c. The last dose of xamoterol after 2 weeks of treatment still produced the same responses. Ketotifen did not influence these effects of xamoterol on resting haemodynamics. The first dose of xamoterol caused a rightward shift of the exercise‐ and isoprenaline‐induced tachycardia (mean dose ratios±s.e.mean: 1.20±0.05 and 2.46±0.23) and the isoprenaline‐evoked shortening of QS 2 c (dose ratio 3.59±0.68). This rightward shift was even more pronounced after 2 weeks xamoterol treatment. This additional rightward shift after 2 weeks of xamoterol was not affected by ketotifen (mean difference (95% CI) of log transformed dose ratios between placebo and ketotifen: exercise tachycardia 0.001 (−0.03; 0.04); isoprenaline tachycardia 0.03 (−0.15; 0.21); isoprenaline induced shortening of QS 2 c 0.13 (−0.22; 0.48)). Conclusions In humans xamoterol is a partial β 1 ‐adrenoceptor agonist with positive chrono‐ and inotropic effects at rest and antagonistic properties under conditions of β‐adrenoceptor stimulation. These effects were well maintained after chronic dosing with no signs of β 1 ‐adrenoceptor desensitization. Ketotifen does not change the β‐adrenoceptor mediated responses of xamoterol after chronic dosing.
Type of Medium:
Online Resource
ISSN:
0306-5251
,
1365-2125
DOI:
10.1046/j.1365-2125.1999.00854.x
Language:
English
Publisher:
Wiley
Publication Date:
1999
detail.hit.zdb_id:
1498142-7
SSG:
15,3
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