Cf. Cartheuser et al., EFFECTS OF DOTARIZINE ON PERIPHERAL AND PULMONARY CIRCULATION AND CARDIAC DYNAMICS IN DOGS, Pharmacology, 48(3), 1994, pp. 187-193
The cardiovascular effects of dotarizine in 10-min intravenous infusio
ns were studied in thiopental-anesthetized dogs. The effects of dotari
zine 0.024 mg/kg/min almost paralleled those of saline controls; 0.079
mg/kg/min dotarizine significantly raised the stroke index and ejecti
on fraction, and, at a rate of 0.25 mg/kg/min, further effects appeare
d and were dose-dependent. Dotarizine produced arterial dilation in bo
th systemic and pulmonary circulation: the total peripheral resistance
dropped, femoral artery flow rose; aortic and pulmonary artery mean a
nd diastolic pressures declined, and systolic pressures remained almos
t stable. A trend of bradycardia and pulmonary artery pressure reducti
on persisted for 30 min. As compared with the reduced total peripheral
resistance, aortic pressure fell only moderately because of rising ca
rdiac output due to a higher ejection fraction and stroke volume. Card
iac preload tended to decline; contractility tended to increase. Cardi
ac performance remained stable while myocardial oxygen consumption ten
ded to fall, as did the pressure-rate product and the tension time ind
ex. Dotarizine exerted direct cardiovascular effects similar to those
of the 5-HT2-receptor antagonist ketanserin and, more generally, to ca
lcium channel blockers rather than to alpha-adrenoceptor blockers.