General pharmacology of ramipril.
General pharmacological properties of (+)-(1S,3S,5S)-2-[(S)-N-[(S)-1-ethoxycarbonyl-3-phenyl-propyl] alanyl]-2-azabicyclo[3.3.0]octane-3-carboxylic acid (ramipril, Hoe 498), a new prodrug non-sulfhydryl angiotensin converting enzyme inhibitor and its active diacid metabolite, ramiprilat, were examined. Both ramipril and ramiprilat were without effect on basal central and autonomic nervous systems in rats and mice. Ramipril given intravenously to anaesthetized normotensive dogs produced a slight fall in blood pressure but did not significantly alter other cardio-hemodynamic functions. Also, ramiprilat was without effect on isolated atria and airway resistance of guinea pigs. Oral administration of ramipril to dogs increased renal blood flow but did not significantly affect other renal parameters, for example, glomerular filtration rate and electrolyte excretion. Ramipril produced a competitive inhibition of late proximal tubular secretion which points to in part renal secretory excretion of ramipril and/or its metabolites. Compared to urea-induced diuresis in rats, ramipril was without direct diuretic activity. Ramipril exerted little, if any, influence on gastric bile and pancreatic secretion or intestinal transit in rats, as well as on concentration of glucose and lipoproteins, blood coagulation, platelet aggregation and vascular permeability in rats, rabbits or dogs. The carrageenin-induced rat paw edema was enlarged by ramipril, but there was no such effect on serotonin-, dextran- or ovalbumin-induced edemas which in contrast to carrageenin do not involve bradykinin. Thus, undesired cutaneous reactions might result from locally released bradykinin.(ABSTRACT TRUNCATED AT 250 WORDS)
Omosu
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Pharma Research Laboratories, Hoechst Japan Limited, Saitama.
Komine
I
I
Becker
R H
RH
Schölkens
B A
BA
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001341:Autonomic Nervous System / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D002319:Cardiovascular System / Q000187:drug effects; D002415:Cats; D002490:Central Nervous System / Q000187:drug effects; D004064:Digestive System / Q000187:drug effects; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D008297:Male; D008660:Metabolism / Q000187:drug effects; D051379:Mice; D011758:Pyrroles / Q000494:pharmacology; D011817:Rabbits; D017257:Ramipril / Q000031:analogs & derivatives; D051381:Rats; D013045:Species Specificity
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001643:Bridged Bicyclo Compounds; D001952:Bridged-Ring Compounds; D011758:Pyrroles; C052549:ramiprilat; D017257:Ramipril