Description
Xamoterol fumarate is a cardioselective partial beta-agonist, the first of its class to be
developed for use in heart failure. The main advantage of xamoterol fumarate as a
cardiotonic lies in the fact that its beta-blocking effect exerted during high sympathetic
drive will protect the heart from overstimulation. It is claimed to be a viable but safer
alternative to digoxin.
Description
Xamoterol is a partial agonist of β
1-adrenergic receptors (β
1-ARs) with an EC
50 value of 80 nM for the generation of cyclic AMP (cAMP) in neonatal rat cardiomyocyte cultures. It increases spontaneous contraction of isolated rat right atria (EC
50 = 4.67 nM).
In vivo, xamoterol increases heart rate in beagle dogs (ED
50 = 3.2 μg/kg) and in a rat model of spontaneous heart failure (ED
50 = 6 μg/kg), an effect that is reversed by the selective β
1-AR antagonist betaxolol but not the selective β
2-AR antagonist ICI 118551 . Formulations containing xamoterol have been used in the treatment of heart failure.
Chemical Properties
Crystallizes in ethanol, melting point 168-169℃ (decomposition).
Originator
ICI (United Kingdom)
Uses
Xamoterol Hemifumarate, is a β1-adrenoceptor-selective partial agonist.
Uses
Stimulant (cardiac).
Biological Activity
β 1 -adrenoceptor-selective partial agonist (pA 2 values are 7.4-7.8 and 5.2-6.2 at β 1 - and β 2 -adrenoceptors respectively).
References
[1] R N WILLETTE. In vitro and in vivo characterization of intrinsic sympathomimetic activity in normal and heart failure rats.[J]. Journal of Pharmacology and Experimental Therapeutics, 1999, 289 1: 48-53.
[2] M T KOWALSKI. Comparison of the effects of xamoterol and isoprenaline on rat cardiac beta-adrenoceptors: studies of function and regulation.[J]. British Journal of Pharmacology, 1990, 99 1: 27-30. DOI:
10.1111/j.1476-5381.1990.tb14648.x[3] A. NUTTALL H. M S. THE CARDIOVASCULAR EFFECTS OF ICI 118,587: A β1-ADRENOCEPTOR PARTIAL AGONIST[J]. British Journal of Pharmacology, 1982, 77 2: 381-388. DOI:
10.1111/j.1476-5381.1982.tb09309.x
