Effects of betaxolol, a new beta 1 selective blocker, on canine ventricular arrhythmias.

Abstract

Abstract-Antiarrhythmic effects of a new beta 1 selective adrenoceptor blocker, betaxolol, were examined in comparison with those of atenolol using two canine ventricular arrhythmia models (adrenaline arrhythmia and digitalis arrhythmia). Both betaxolol and atenolol suppressed adrenaline arrhythmia, and the minimum effective plasma concentration of betaxolol for this arrhythmia model was deter mined to be less than 10 ng/ml.However, on digitalis arrhythmia, both beta blockers were ineffective, even though the high doses used in these experiments, 3 mg/kg for betaxolol and 5 mg/kg for atenolol, showed significant hypotensive effects.The present results suggest that betaxolol and atenolol may be expected to be clinically effective on arrhythmias related to increased sympathetic tone.

Effects of antiarrhythmic drugs on canine ventricular arrhythmia models: Which electrophysiological characteristics of drugs are related to their effectiveness?

“…As reported earlier [1,2,[5][6][7][8][9][11][12][13][14][15][16][17][18]20,21,[23][24][25][26][27][28][29][30][31][32], mongrel and beagle dogs of either sex, as well as female beagle dogs, weighing about 7-15 kg, were anesthetized initially with thiopental sodium. After intubation, 1.0% halothane, vaporized with 100% oxygen, was administered with a volume-limited ventilator (20 ml/kg, 15 strokes/min).…”

“…Carvedilol is an investigational beta blocker and was effective on digitalis and adrenaline arrhythmias [19], and the IC~0 for digitalis arrhythmia was 4.6 (2.9-30; n = 44, r = -0.34, p < 0.05) ~g/ ml. N-696 is an investigational beta blocker and was effective on coronary ligation and adrenaline arrhythmias, but was not effective on digitalis arrhythmia [8], and the IC~0 for 24-hour coronary ligation arrhythmia was 28.0 (21.3-100; n = 48, r = -0.35, p < 0.05) ~g/ml.Betaxolol is an investigational beta blocker and was effective only on adrenaline arrhythmia [16], and the IC50 for adrenaline arrhythmia was 5.4 (3.2-7.9; n = 15, r = -0.59, p < 0.01) ng/ml. Bepridil, diltiazem, gallopamil and verapamil were effective only on adrenaline arrhythmia [9,11,23], and the ICs0 s for adrenaline arrhythmia were 0.43 (0.41-2; n --26, r = -0.45, p < 0.05), 0.032 (0.022-0.053; n = 21, r = -0.63, p < 0.01), 0.032 (0.024-0.040; n = 19, r = -0.61, p < 0.01), and 0.036 (0.028-0.047; n = 27, r = -0.75, p < 0.01) ~g/ml, respectively.…”

Arrhythmia Models for Drug Research: Classification of Antiarrhythmic Drugs

“…-channel-blocking drugs verapamil (10) and gallopamil (44) did not suppress these arrhythmias and also β-blockers were not effective unless high doses to produce Na + -channel-blocking effects were given (10,13,14,17,19,45). Pure K + -channel-blocking drugs that we tested did not suppress these arrhythmias (6, 46 -49), but amiodarone given intravenously suppressed the two-stage coronary ligation arrhythmia, but the plasma concentration was not determined in this experiment (50).…”

“…In this model, Na + -channel blockers were tested, including bisaramil, disopyramide, lidocaine, and flecainide, which also suppressed this DAD-induced PVC. β-Blockers were not effective unless high doses to suppress Na + channels were given (17,19,45,69). K + -channel-blocking drugs did not suppress this arrhythmia (6, 46 -49), but intravenous amiodarone, probably by its Na + -channel-blocking effect, suppressed this digitalis arrhythmia (50).…”

“…Since adrenaline stimulates cardiac β receptors, all the β blockers were thought to be and actually were effective in low β-blocking doses at low plasma concentrations (13,17,19,45,69). Other important drugs that were effective were Ca 2+ -channel blockers.…”