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COMPARATIVE ANTIDYSRHYTHMIC AND HAEMODYNAMIC EFFECTS OF ORALLY OR INTRAVENOUSLY ADMINISTERED MEXILETINE AND ORG 6001 IN THE ANAESTHETIZED RAT
Author(s) -
MARSHALL R.J.,
MUIR A.W.,
WINSLOW E.
Publication year - 1981
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1981.tb09982.x
Subject(s) - mexiletine , disopyramide , pharmacology , procainamide , anesthesia , medicine , ventricular fibrillation
1 The antidysrhythmic and haemodynamic effects of the aminosteroid, Org 6001, were studied in the rat anaesthetized with pentobarbitone. Mexiletine was used for comparison 2 Both Org 6001 (2–10 mg/kg) and mexiletine (1 mg/kg) given intravenously antagonized the development of dysrhythmias evoked by acute coronary artery ligation in rats 3 In antidysrhythmic doses, Org 6001 and mexiletine exerted only moderate and transient hypotension and depression of cardiac contractility (assessed from LV d P /d tmax ). Org 6001 did, however, induce a more sustained bradycardia 4 Effective oral doses of Org 6001 (20–100 mg/kg) were similar to those of mexiletine, disopyramide and propafenone 5 Oral Org 6001 (100 mg/kg) was effective for 18 h whereas mexiletine (100 mg/kg) failed to protect against evoked dysrhythmias 3 h after dosing 6 Org 6001 and mexiletine differed in their actions on ventricular fibrillation threshold (VFT). Org 6001 (100 mg/kg orally 12 h before ligation) prevented the decrease in VFT produced by coronary ligation whereas mexiletine (100 mg/kg orally) had no effect. When administered intravenously, mexiletine (but not Org 6001) increased VFT in normal ventricular muscle.