Anticholinergics antiarrhythmic activity

Disopyramide phosphate is used orally for the treatment of certain ventricular and atrial arrhythmias. Despite its structural dissimilarity to procainamide (Fig. 26.10), its cardiac effects are very similar. Disopyramide is rapidly and completely absorbed from the gastrointestinal tract. Peak plasma level is usually reached within 1 to 3 hours, and a plasma half-life of 5 to 7 hours is common. Approximately half of an oral dose is excreted unchanged in the urine. The remaining drug undergoes hepatic metabolism, principally to the corresponding N-dealkylated form. This metabolite retains approximately half the antiarrhythmic activity of disopyramide and also is subject to renal excretion. Adverse effects of disopyramide frequently are observed. These effects are primarily anticholinergic in nature and include dry mouth, blurred vision, constipation, and urinary retention. 

Because of the relationship of the reduced ring system to piperazine, various derivatives have been studied and found to have activity on the central nervous system (CNS). Thus the compound 68 was found to be more active than the corresponding pyrido compound (69) in the mouse amphetamine-induced toxicity and hypermotility tests. Certain phenothiazine derivatives are the subject of recent patents. " Various other 2-substituted perhydropyrrolo[l,2-a]pyrazines have been patented as sympatholytics, antihistaminic, anticholinergic, and antitremorine compounds, CNS depressants,antiarrhythmics, ° coronary dilators, and anticonvulsants and analgesics. " ... 

---