@article {SCHUSTER213, author = {DANIEL P. SCHUSTER and BENEDICT R. LUCCHESI and NANCY L. NOBEL and MICHAEL N. MIMNAUGH and RAYMOND E. COUNSELL and FRANK J. KNIFFEN}, title = {THE ANTIARRHYTHMIC PROPERTIES OF UM-272, THE DIMETHYL QUATERNARY DERIVATIVE OF PROPRANOLOL}, volume = {184}, number = {1}, pages = {213--227}, year = {1973}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {The quaternary derivative of propranolol, UM-272, [N,N-dimethyl-1-isopropylamino-3-(1-naphthyloxy)-propan-2-ol], was evaluated for its antiarrhythmatic effects. Ouabaininduced ventricular tachycarcdia in the anesthetized dog was reversed by UM-272 in a dose of 2 to 3 mg/kg i.v. Pretreatment of anesthetized dogs with UM-272, 10 mg/kg i.v., lowered the incidence of ventricular fibrillation associated with acute occlusion or release of the left anterior descending coronary artery. The antifibrillatory action of UM-272 was accompanied by a significant reduction in the frequency of ventricular premature beats during the periods of ischemia or upon restoration of blood flow to the ischemic myocardium. Ectopic ventricular rate in conscious dogs 48 hours after two-stage coronary artery ligation averaged 103 {\textpm} 14 (S.E.M.) beats/min before and 16 {\textpm} 11 beats/min after UM-272 (2.5-10 mg/kg i.v.). The duration of antiarrhythmic activity was in excess of 60 minutes. UM-272 (10-8 M) prevented or reversed acetylstraphanthidin-induced arrhythmias in the isolated rabbit heart. Nerve impulse transmission in the desheathed or myelinated frog sciatic nerve trunk was not prevented by UM-272 (1O-8 M), which suggests a lack of local anesthetic activity. The pA2, value for UM-272 calculated from chranotropic concentration-effect curves to isopraterenol in spontaneously beating rabbit atnial strips was 4.35 (cf. propranolol 8.7). Inatropic dose-response curves to isoproterenol in the dog demonstrated a lack of beta adrenergic receptor blocking activity for UM-272. The results indicate that UM-272, a quaternary compound without demonstrable beta adrenergic receptor blocking activity and local anesthetic activity, possesses anti-arrhythmic properties. {\textcopyright} 1973 by The Williams \& Wilkins Company}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/184/1/213}, eprint = {https://jpet.aspetjournals.org/content/184/1/213.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }