Pharmacological profile of the new antidepressant levoprotiline.
The pharmacological properties of a new antidepressant, levoprotiline ((-)-R-a-[(methylamino)methyl]-9,10-ethanoanthracene-9(10H)- ethanol hydrochloride, CGP 12103 A, CAS 76496-69-0) were investigated. 1. Central nervous system: Levoprotiline did not have any marked effects on the general behaviour of mice and rats at low doses, however it slightly suppressed the righting reflex and spontaneous motor activity of mice at higher doses. In rats, chewing behaviour and salivation were observed at higher doses. Levoprotiline had no effects on the traction test (mice) and inclined screen test (rats). Levoprotiline induced a slight drowsy EEG pattern, the effect being similar to that of typical antidepressants such as maprotiline or imipramine but the degree of potency of levoprotiline was less than that of the latter two drugs. Levoprotiline and maprotiline did not inhibit the arousal response induced by physostigmine, while imipramine clearly suppressed the response. 2. Respiratory and cardiovascular system: Heart rate decrease and QT prolongation were observed in anesthetized dogs. In an in vitro study, levoprotiline caused only slight stimulation of noradrenaline transmission in the isolated guinea pig atrium. 3. Smooth muscle: The effects of levoprotiline on the contractile response to histamine, acetylcholine and serotonin in the isolated guinea pig ileum were compared with those of maprotiline or imipramine. While levoprotiline potently inhibited the contractile response to histamine, its inhibition of acetylcholine-induced contraction was the weakest of the three compounds studied. No remarkable effect was observed in serotonin induced contractions.(ABSTRACT TRUNCATED AT 250 WORDS)
Noguchi
S
S
Pre-clinical Research Department, Ciba-Geigy Limited, Takarazuka, Japan.
Okada
M
M
Inukai
T
T
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001777:Blood Coagulation / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D002319:Cardiovascular System / Q000187:drug effects; D004285:Dogs; D004569:Electroencephalography / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D007082:Ileum / Q000187:drug effects; D008055:Lipids / Q000097:blood; D008297:Male; D008376:Maprotiline / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D009130:Muscle, Smooth / Q000187:drug effects; D010830:Physostigmine / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D012137:Respiratory System / Q000187:drug effects; D014563:Urodynamics / Q000187:drug effects
D000928:Antidepressive Agents; D001786:Blood Glucose; D008055:Lipids; D008376:Maprotiline; C027299:hydroxymaprotilin; D010830:Physostigmine