Tetramisole (hydrochloride)

Tetramisole hydrochloride is an orally active, selective inward rectifier potassium channel agonist with an EC₅₀ of approximately 30 μM for the Kir2.1 subunit. Tetramisole hydrochloride is also an anti-nematode agent that blocks neuromuscular transmission by non-competitive depolarization. Tetramisole hydrochloride promotes the forward transport of Kir2.1 channels, hyperpolarizes the resting potential (RP), shortens the action potential duration (APD), inhibits intracellular calcium overload and the PKA signaling pathway, and exerts anti-arrhythmic and anti-myocardial remodeling activities. Tetramisole hydrochloride can be used in cardiac electrophysiology research and research related to myocardial ischemia and heart failure^[1][2]. In Vitro:Tetramisole hydrochloride (1-100 μM) enhances the inward rectifier potassium current in rat ventricular myocytes (ARVMs) in a concentration-dependent manner in whole-cell patch clamp experiments, hyperpolarizes the resting potential (RP) and shortens the action potential duration (APD₉₀), but has no significant effect on other ion channels such as L-type calcium current (I_Ca-L) and sodium current (I_Na)^[1].
Tetramisole hydrochloride (10-30 μM; 24 h) significantly inhibits isoproterenol (Iso)-induced intracellular calcium overload in H9c2(2-1) cardiomyocyte calcium imaging experiments, an effect that can be reversed by the I_K1 channel blocker BaCl2^[1].
Tetramisole hydrochloride (30 μM; 48 h) can upregulate the expression level of Kir2.1 in H9c2(2-1) cells^[1].
In Vivo:Tetramisole (0.54 mg/kg; intravenous injection; single dose; 3 minutes pretreatment) hydrochloride significantly reduces the number and duration of ventricular arrhythmias and the incidence of ventricular fibrillation in the Sprague-Dawley rat model of myocardial infarction induced by coronary artery ligation, and this effect is reversed by the I_K1 channel blocker chloroquine (CQ)^[2].
Tetramisole (0.54 mg/kg; intraperitoneal injection; once a day; 10 days) hydrochloride improves cardiac contractile function, reduces cardiomyocyte hypertrophy and interstitial fibrosis, and inhibits the activation of the PKA signaling pathway in the Sprague-Dawley rat model of isoproterenol (Iso)-induced cardiac remodeling, and the effect is dependent on the I_K1 channel activity^[2].