Tolerance and pharmacodynamics of the angiotensin converting enzyme inhibitor 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S,5S)-2- azabicyclo[3.3.0]octane-3-carboxylic acid (Hoe 498) in healthy volunteers.
In healthy volunteers a single oral dose of 5 mg 2-[N-[(S)-1-Ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S, 5S)-2-azabicyclo[3.3.0]octane-3-carboxylic acid (Hoe 498) was well tolerated. Following 5 mg Hoe 498 plasma angiotensin converting enzyme (ACE) activity was inhibited by almost 100% up to 8 h. A marked effect on plasma ACE was observed for more than 8 days. Plasma renin activity increased whereas aldosterone plasma levels decreased only slightly. Sodium and potassium excretion was not influenced by the compound. Systolic and diastolic blood pressure was slightly lowered by Hoe 498, whereas no relevant changes in pulse rate were observed.
D000328:Adult; D000450:Aldosterone / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000009:adverse effects / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011188:Potassium / Q000652:urine; D017257:Ramipril; D012083:Renin / Q000097:blood; D012964:Sodium / Q000652:urine; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001643:Bridged Bicyclo Compounds; D001952:Bridged-Ring Compounds; D000450:Aldosterone; D012964:Sodium; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D017257:Ramipril; D011188:Potassium