The chronotropic cardiac effects of
alinidine were studied in the conscious dog with chronic
atrioventricular block.
Alinidine at 0.5 - 4 mg/kg, i.e., at plasma concentrations between 42 +/- 2 and 1625 +/- 371 ng/ml, initially increased atrial rate dose-dependently. This effect fell off rapidly, but atrial
bradycardia was never observed. After
atropine and
pindolol, which raised basal atrial rate,
alinidine (2 mg/kg) decreased atrial rate, whereas after phenoxy-benzamine,
yohimbine or
phentolamine, it produced atrial effects identical to those observed under basal conditions, i.e., initial
tachycardia and no
bradycardia.
Alinidine dose-relatedly decreased ventricular rate. None of the pretreatments modified the maximal ventricular
bradycardia, but interestingly after
pindolol or
yohimbine this effect developed more rapidly (maximal
bradycardia between 3 and 5 against 30 min) and then declined progressively.
Alinidine did not modify mean blood pressure at any dose. After
atropine,
phenoxybenzamine or
phentolamine,
alinidine remained without effect on mean blood pressure, but after
pindolol or
yohimbine, a hypotensive effect appeared concomitantly with the reduction of the ventricular
bradycardia. These results show that the initial atrial cardioacceleration due to
alinidine results from a direct vagolytic action of this
drug and that the absence of atrial
bradycardia results from buffering by the vagolytic effect and/or a relatively low basal atrial rate. They also suggest that the ventricular
bradycardia does not involve either the
muscarinic cholinoceptors or the alpha- or beta-
adrenoceptors, though the results obtained after
pindolol or
yohimbine suggest possible involvement of a fall in sympathetic tone by stimulation of presynaptic or central alpha2-adrenoceptors, particularly in the persistence of the bradycardic effect.(ABSTRACT TRUNCATED AT 250 WORDS)