Xamoterol (hemifumarate)

Xamoterol (Corwin; ICI 118587) hemifumarate is an orally active and selective β₁-adrenoceptor partial agonist. Xamoterol hemifumarate acts as agonist at low sympathetic tone, antagonist at high sympathetic tone, with context-dependent cardiovascular effects including modulated heart rate, blood pressure, and cardiac output. Xamoterol hemifumarate can be used for the research of heart failure, postural hypotension, and ischemic heart disease^{[1][2][3][4][5][6][7]}. In Vitro:Xamoterol (0.5 nM-50 μM; 2 min) hemifumarate produces weak β₂-adrenoceptor-mediated relaxant effects in progesterone-pretreated rat uterus, and non-specific, non-β-adrenoceptor-mediated inhibitory effects in guinea-pig ileal and tracheal preparations, with no β-adrenoceptor-mediated activity in oestrogen-pretreated uterine or rat vas deferens preparations^[2].
Xamoterol (70 min) hemifumarate displays selective affinity for β₁-adrenoceptors, with a pK_D of 7.25 in guinea-pig left atrial membranes (β₁) and a pK_D of 5.24 in guinea-pig uterine membranes (β₂), representing a 100-fold preference for β₁ sites^[2].
Xamoterol (0.2 nM-6 μM) hemifumarate acts as a β₁-selective partial agonist in isolated male AP rat right atria, producing a maximal rate stimulation response 65-70% that of isoprenaline with an EC₅₀ of 4.67 nM^[3]. In Vivo:Xamoterol (0.1-33 μg/kg; i.v.; single bolus injection) hemifumarate acts as a β₁-selective partial agonist in anaesthetised, catecholamine-depleted rats with an ED₅₀ of 0.361 μg/kg^[3].
Xamoterol (600 μg/kg/h; s.c.; continuous infusion; 6 days) hemifumarate does not induce cardiac β-adrenoceptor down-regulation or alter receptor-adenylate cyclase coupling in normal rats^[3].
Xamoterol hemifumarate acts as a β₁-adrenoceptor partial agonist in anaesthetised areflexic dogs, demonstrating 43% of isoprenaline's intrinsic sympathomimetic activity at β₁-receptors without β₂-receptor stimulation^[5].