General pharmacology of the novel angiotensin converting enzyme inhibitor alacepril. 2nd communication: Effects on central nervous and sensory systems and on the other functions.
The effects of 1-[(S)-3-acetylthio-2-methylpropanoyl]-L-prolyl-L-phenylalanine (alacepril, DU-1219), an orally active angiotensin converting enzyme inhibitor, on the central nervous and sensory systems and on several other functions were compared with those of captopril in the experimental animals. Alacepril at the high oral dose of 600 mg/kg prolonged the hexobarbital sleeping time and potentiated the reserpine-induced hypothermia in mice. However, alacepril at the same dose did not affect the general behavior, convulsions induced by maximal electroshock, pentetrazol and strychnine, active avoidance in mice and body temperature in rats. In addition, alacepril (200 mg/kg i.v.) has little effect on general behavior in mice. Captopril at over 107 mg/kg p.o. produced eyelid closure and at 320 mg/kg prolonged the hexobarbital sleeping time. A metabolite of alacepril, desacetylalacepril (DU-1227) (200 mg/kg i.v.), caused salivation in mice. Alacepril and DU-1227 at 60 mg/kg i.v. were without effect on flexor reflex and spontaneous electroencephalogram (EEG) in cats, while captopril at the equimolar dose depressed the flexor reflex and showed a tendency to increase the beta 2-band relative power of the cortical EEG. Alacepril and captopril neither affected the writhing syndrome induced by acetic acid nor that by phenylquinone in mice. Local anesthetic and irritant activities in rabbits and effect on neuromuscular junction in anesthetized rats were not observed with the two compounds. Alacepril at the oral dose of 0.1 mg/kg potentiated the carrageenin-induced edema in rats. However, the effect was one third that of captopril. Alacepril and captopril did not affect the increased vascular permeability by acetic acid in mice.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D000927:Anticonvulsants; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D002216:Captopril / Q000031:analogs & derivatives* / Q000494:pharmacology; D002415:Cats; D002490:Central Nervous System / Q000187:drug effects*; D005260:Female; D008297:Male; D051379:Mice; D009469:Neuromuscular Junction / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D012018:Reflex / Q000187:drug effects; D012677:Sensation / Q000187:drug effects*; D012890:Sleep / Q000187:drug effects
D000927:Anticonvulsants; D000959:Antihypertensive Agents; C048162:desacetyl-alacepril; D002216:Captopril; C046835:alacepril