Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q96S42 (nodal)
 22,877 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Moricizine (moracizine, ethmozine) is an orally active phenothiazine derivative with direct myocardial Class I antiarrhythmic activity and minimal CNS effects. Placebo-controlled studies have confirmed its efficacy in suppressing nonmalignant ventricular arrhythmias (premature ventricular complexes, couplets and runs of nonsustained ventricular tachycardia), including those refractory to previous antiarrhythmic therapy. Preliminary findings have indicated that moricizine is also effective in suppressing atrial ectopic activity, atrioventricular nodal re-entry tachycardia and Wolff-Parkinson-White tachycardias involving accessory pathways. As with other oral antiarrhythmics, malignant ventricular arrhythmias (sustained ventricular tachycardia and ventricular fibrillation) have been shown, both on noninvasive monitoring and programmed electrical stimulation, to be less susceptible to suppression by moricizine than nonmalignant ventricular arrhythmias. The therapeutic potential of moricizine is enhanced by its relatively low incidence of extra-cardiac adverse effects (predominantly gastrointestinal and neurological) and its lack of significant cardiodepressant activity in patients with normal or mildly to moderality depressed left ventricular function. Moricizine has proved to be more effective than disopyramide and propranolol in suppressing ventricular ectopic activity, of comparable efficacy to quinidine, but less effective than encainide and flecainide. The drug appears to be particularly suited to the suppression of ventricular ectopy in patients with preexisting left ventricular dysfunction. Further studies are required to confirm its long term efficacy and effects on mortality when used prophylactically in patients at increased risk of sudden cardiac death.
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PMID:Moricizine. A review of its pharmacological properties, and therapeutic efficacy in cardiac arrhythmias. 220 81

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of the Class I antiarrhythmic agent moricizine hydrochloride are reviewed. Moricizine is chemically similar to the phenothiazines but does not appear to block dopaminergic receptors. Its major electrophysiologic actions are a concentration-dependent decrease in maximum rate of phase 0 depolarization; increased rates of phase 2 and 3 repolarization, decreased action potential duration, and decreased effective refractory period. Moricizine causes a dose-related prolongation of the PR interval and of AV nodal, infranodal, and intraventricular conduction times but has little effect on ventricular repolarization. The antiarrhythmic and electrophysiologic effects are not correlated with plasma concentrations of the drug or its metabolites. Moricizine reduces the occurrence of ventricular premature contractions (VPCs), couplets, and nonsustained ventricular tachycardia. It appears to suppress symptomatic nonsustained ventricular tachycardia, sustained ventricular tachycardia, and ventricular fibrillation or flutter. Moricizine appears to be as effective as quinidine and more effective than disopyramide, propranolol, and imipramine but less effective than flecainide and encainide at reducing VPCs. Moricizine continues to be evaluated in the Cardiac Arrhythmia Suppression Trial, which was designed to assess the long-term benefit of arrhythmia suppression in patients with left ventricular dysfunction after myocardial infarction. Moricizine seems to be better tolerated than quinidine, disopyramide, and imipramine and to have less proarrhythmic potential than flecainide or encainide. Noncardiac adverse effects include dizziness, nausea, and headache. Cimetidine appears to decrease moricizine clearance, and decreased theophylline clearance has been reported in subjects given moricizine. The usual adult dosage of moricizine hydrochloride is 600-900 mg/day given in three divided doses; an every-12-hour regimen may be used in some patients. Because of the risk of proarrhythmic effects, indications are limited to treatment of documented life-threatening arrhythmias. Moricizine will compete with other agents as first-line therapy for life-threatening arrhythmias.
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PMID:Moricizine: a new class I antiarrhythmic. 227 51

The electrophysiologic effects and antiarrhythmic efficacy of moricizine HCl (1.5 to 2.0 mg/kg intravenously, and 600 to 800 mg orally/24 hours) were studied using electrophysiologic testing, ambulatory electrocardiographic monitoring, exercise stress testing and transesophageal stimulation of the left atrium. Moricizine HCl had no significant effects on the sinus node in patients with normal nodal function and did not depress sinoatrial conduction time even in patients with serious node dysfunction. Moricizine HCl significantly lengthened the following intervals: PA (32 +/- 5 to 40 +/- 5 ms), AH (82 +/- 13 to 92 +/- 12 ms), HV (45 +/- 12 to 50 +/- 12 ms), paced cycle length 1:1 atrioventricular node conduction (340 +/- 14 to 352 +/- 14 ms) and paced cycle length 1:1 ventriculoatrial conduction (300 +/- 14 to 400 +/- 13 ms). The refractory periods of atrium, atrioventricular node and ventricular myocardium did not change significantly, and there was no alteration of the QRS or QT intervals. The drug abolished anterograde and retrograde conduction over the accessory pathway and increased the refractory period of accessory pathway in all patients. Intravenous moricizine HCl terminated and prevented tachycardia in 72% and 68% of the patients, respectively. Oral moricizine HCl (600 to 800 mg/24 hours) prevented tachycardia in 40% of patients with a preexcitation syndrome. Intravenous moricizine HCl terminated atrioventricular nodal reentrant paroxysmal tachycardia in 66% of patients, whereas 40% responded to the oral drug. Moricizine HCl 600 to 800 mg/24 hours suppressed ventricular premature beats in 60% of patients. A similar drug, Ethacizine, had the same electrophysiologic effects as moricizine HCl but was more potent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical, electrophysiologic and antiarrhythmic efficacy of moricizine HCl. 331 May 84

Moricizine HCl, an antiarrhythmic phenothiazine drug, was investigated for its efficacy against ventricular tachycardia (VT) in a group of 60 patients from 8 institutions using electrophysiologic testing before and after oral administration. Moricizine HCl significantly prolonged PR, QRS, AH and HV intervals and cycle length for atrioventricular nodal block, but had minimal or no effect on repolarization or cardiac refractory periods. Induction of sustained VT (in 33 patients) and nonsustained VT (in 14 patients) occurred at baseline. During moricizine HCl therapy, sustained VT was induced in 31 patients and nonsustained VT in 7 patients. In individual patients, suppression of VT induction was obtained in 18% of patients with sustained VT and in 27% of patients with nonsustained VT. Cycle length of induced VT was significantly prolonged by moricizine HCl therapy. During prospective follow-up of 37 patients, electrophysiologic study predicted recurrence of nonrecurrence of VT with a sensitivity value of 82% and specificity of 65%.
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PMID:Electrophysiology of Ethmozine (moricizine HCl) for ventricular tachycardia. 331 May 88