Rotigaptide is a novel antiarrhythmic peptide that enhances gap junction (GJ) intercellular conductance between cardiomyocytes without changing membrane conductance. rotigaptide could suppress the onset of arrhythmogenic spatially discordant alternans (SDA) and may protect guinea pig hearts against ischemia-induced arrhythmia. Other animal studies found that rotigaptide could hinder spontaneous ventricular arrhythmia and prevent ventricular tachyarrhythmia during acute ischemia in open chest dogs. These findings support that ventricular arrhythmias could be prevented by enhancing cell-to-cell coupling with rotigaptide. Rotigaptide's Molecular Formula is C28H39N7O9, and the chemical structure is shown in Fig 1.
Fig 1. The general chemical structure of rotigaptide (Liu et al. 2014).
Pharmacologic action
At the concentration of atrial conduction, rotigaptide had no obvious blocking activity in cardiac refractory phase and did not cause any arrhythmia. This drug has no effect on cardiac contractility, heart rate and blood pressure, and does not exert negative muscle effect on people. After rotigaptide treatment, there was no increase in infarct volume. In fact, infarct volume decreased after medication.
Function
The gap junction (GJ) modifier rotigaptide protects the heart against ventricular arrhythmias during 33oC and 30oC by increasing ventricular conduction velocity (CV), delaying the onset of arrhythmogenic spatially discordant alternans (SDA), reducing repolarization heterogeneity, but it does not affect the expression of gap connexin. Enhancing cell-to-cell coupling by rotigaptide might be a novel approach to prevent recurrent ventricular arrhythmias in patients undergoing therapeutic hypothermia (TH).
Pharmacokinetics and metabolism
Whether it is experiment or theory, this drug all maymay affect connexin gating, expression and distribution, and increase atrial gap junctional intercellular communication (GJIC). This drug can specifically inhibit the dephosphorylation of connexin (Cx) 43 terminal serine residues, that is, important regulators of connexin gating.the serine residue at the end of connexin (Cx)43, an important regulator of connexin gating. The phosphorylation of connexin not only affects gating but also affects the expression and renewal of connexin. Therefore, it is not possible to exclude the effect of this drug on connexin expression. Experiments have shown that this drug can increase the expression of connexin (Cx) 43 in neonatal rat myocardium, thus increasing gap junction formation.the formation of gap junctions. Roitgitde reduced ventricular effective refractory period (ERP), increased ventricular fibrillation threshold (VFT) and decreased ventricular arrhythmia induced by heart failure, but did not affect connexin expression.
References:
Yu-Cheng Hsieh, Jiunn-Cherng Lin, Chen-Ying Hung, Cheng-Hung Li, Shien-Fong Lin, Hung-IYeh, Jin-Long Huang, Chu-Pin Lo, KetilHaugan, Bjarne D Larsen, Tsu-JueyWu, Gap junction modifier rotigaptide decreases the susceptibility to ventricular arrhythmia by enhancing conduction velocity and suppressing discordant alternans during therapeutic hypothermia in isolated rabbit hearts Heart Rhythm 2016; 13(1): 251–261.
