Cardiovascular effects of amezinium in humans during passive upright tilt in comparison with norfenefrine and dihydroergotamine.
20 min after single i.v. administration of 10 mg 4-amino-6-methoxy-1-phenyl-pyridazinium methyl sulfate (ameziniummetilsulfate, LU 1631, Regulton), in the following briefly called amezinium, a new antihypotensive agent, was studied in comparison with 10 mg norfenefrine i.m. and 1 mg dihydroergotamine i.m. during orthostatic stress on a tilt table in a total group of 29 healthy volunteers with stable cardiovascular conditions. The study of each substance was preceded by a control tilting test. After amezinium a higher systolic blood pressure of 10 to 15 mmHg in comparison with the control test was maintained during 5 min upright tilt with both a smaller increase in the rise of heart rate and decrease in stroke volume. In comparison with control, pulse pressure was also clearly increased whereas cardiac output and total peripheral resistance were not significantly different. The increase in stroke volume in comparison with control was a result of the positive inotropic effect on the one hand, which could be seen in both a diminished prolongation of the preejection period and increase in the PEP/LVET ratio, and an increased venous return to the heart on the other hand. Systolic blood pressure and heart rate after norfenefrine were principally similar to those after amezinium, whereas the effect on stroke volume was of minor magnitude because of the absence of a positive inotropic action. Moreover, cardiac output decreased more with higher total peripheral resistance in comparison to control. Besides a slight reduction in heart rate, dihydroergotamine did not reveal any significant differences from control during orthostatic stress. At the dose studied, amezinium seemed to produce a better adaptation to passive upright tilt than the reference substances.
D015078:2-Hydroxyphenethylamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004087:Dihydroergotamine / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D009655:Octopamine / Q000031:analogs & derivatives*; D010627:Phenethylamines / Q000494:pharmacology*; D011187:Posture; D011724:Pyridazines / Q000494:pharmacology*; D013997:Time Factors
D010627:Phenethylamines; D011724:Pyridazines; D009655:Octopamine; D004087:Dihydroergotamine; D015078:2-Hydroxyphenethylamine; C005310:norfenefrine; C027784:amezinium