Studies on the cardiovascular depressant effects of N-ethyl- and N-benzyl-1,2-diphenylethanolamines in the rat: elucidation of the mechanisms of action.
The influence and mechanisms of action of N-ethyl- and N-benzyl-1,2-diphenylethanolamines (compounds E and B, respectively) on the arterial blood pressure and the heart rate of the rat together with their effects on CaCl2-induced arrhythmias in the rat were investigated. Both E and B in doses of (1.5-12 micromol/kg IV) decreased the arterial blood pressure and the heart rate in a dose-dependent manner. Studies with various receptor blockers, enzyme inhibitors and CaCl2 revealed that E-induced cardiovascular depressant effects were mainly due to CaCl2 channel blocking action and activation of cyclic guanylyl cyclase or release of NO whereas the cardiovascular effects of B seemed to involve both blockade of Ca2+ channels and activation of parasympathetic ganglia. Both compounds (12-14.5 micromol/kg) completely protected the rat against CaCl2 (60 mg kg(-1))-induced tachyarrhythmias. The B compound seemed to be several times more potent than the E compound in its cardiovascular depressant actions. The results suggest the potential usefulness of both compounds in the treatment of hypertension and supraventricular arrhythmias.
Bakheet
D M
DM
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia.
El Tahir
K E
KE
Al-Sayed
M I
MI
El-Obeid
H A
HA
Al-Rashood
K A
KA
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control; D001794:Blood Pressure / Q000187:drug effects; D002122:Calcium Chloride / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000503:physiopathology / Q000517:prevention & control; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D011738:Pyrilamine / Q000494:pharmacology; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D002317:Cardiovascular Agents; D016861:Cyclooxygenase Inhibitors; D004983:Ethanolamines; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; C120418:N-benzyl-1,2-diphenylethanolamine; C120417:N-ethyl-1,2-diphenylethanolamine; D011899:Ranitidine; D011738:Pyrilamine; D002122:Calcium Chloride; D007213:Indomethacin