Zinterol

Zinterol (MJ 9184) is a potent and selective β2-adrenoceptor agonist[1]. Zinterol increases ICa in a concentration-dependent manner with an EC50 of 2.2 nM[2].

Research Areas >> Cardiovascular Disease

Signaling Pathways >> GPCR/G Protein >> Adrenergic Receptor

β2-adrenoceptor[1]

Zinterol (2.5 μg/kg i.v. bolus over 5 s) leads to ventricular arrhythmias including premature ventricular complexes (PVCs) and runs of ventricular tachycardia (VT) in heart failure (HF) rabbits. Zinterol at a lower dose (1 μg/kg i.v, n=4) does not induce ventricular arrhythmias in HF rabbits[3]. Animal Model: In New Zealand White HF rabbits of either sex[3] Dosage: 1.0 or 2.5 μg/kg Administration: Intravenous bolus administration; over 5 seconds Result: 2.5 μg/kg did not significantly alter heart rate or mean arterial blood pressure in either control or HF rabbits. 2.5 μg/kg led to ventricular arrhythmias including PVCs and runs of VT (up to 13 beats long) in 4 of 6 HF rabbits (vs 0 of 5 controls, p<0.01). 1 μg/kg did not induce ventricular arrhythmias in HF rabbits.

[1]. Gwee MC, et al. Pharmacological actions of a new -adrenoceptor agonist, MJ-9184-1, in anaesthetized cats. Br J Pharmacol. 1972 Nov;46(3):375-85.

[2]. Skeberdis VA, et al. Beta-2 adrenergic activation of L-type Ca²⁺ current in cardiac myocytes. J Pharmacol Exp Ther. 1997 Nov;283(2):452-61.

[3]. Desantiago J, et al. Arrhythmogenic effects of beta2-adrenergic stimulation in the failing heart are attributable to enhanced sarcoplasmic reticulum Ca load. Circ Res. 2008 Jun 6;102(11):1389-97.