title: Pharmacological profile of moclobemide, a short-acting and reversible inhibitor of monoamine oxidase type A.
abstract: The novel antidepressant moclobemide is a reversible inhibitor of monoamine oxidase (MAO), preferentially of type A. Moclomide was active in three animal models considered predictive for antidepressant activity: 1) it prevented dose-dependently akinesia and blepharospasm induced in mice and rats by Ro 4-1284, a short-acting amine releasing agent. Prevention of akinesia by moclobemide also depended upon the dose of Ro 4-1284. For comparison also, effects of cimoxatone, harmaline, tranylcypromine and clorgyline are presented: 2) in cats, it selectively and dose-dependently suppressed rapid eye movement sleep without disturbing the sleep-wakefulness cycle; and 3) in the behavioral despair test in mice, it decreased the immobility score to a similar degree as amitriptyline or imipramine. In addition, moclobemide potentiated 5-hydroxytryptophan-induced stereotypies in rats with a potency similar to cimoxatone and with a duration of action of less than 24 hr. Moclobemide had almost no effect on the spontaneous behavior in mice, rats, cats and monkeys. Only in higher doses, marginal sedation and slight impairment in motor performance were seen. Moclobemide did not prevent pilcarpine-induced salivation in mice, demonstrating the absence of anticholinergic activity. Blood pressure and heart rate of freely moving, spontaneously hypertensive rats were only slightly decreased for less than 3 hr. Moclobemide moderately potentiated the pressor effect of p.o. tyramine in rats. In conclusion, the reversible MAO inhibitor moclobemide is active in animal models sensitive to all major drugs used in the treatment of depression. In contrast to imipramine-like antidepressants, it lacks anticholinergic activity and it differs from classic MAO inhibitors by potentiating only weakly the pressor effect of p.o. tyramine.
authors.affiliation: Pharmaceutical Research Department F. Hoffmann-La Roche & Co., Ltd., Basel, Switzerland.
authors.forename: W P
authors.initials: WP
authors.lastname: Burkard
authors.forename: E P
authors.initials: EP
authors.lastname: Bonetti
authors.forename: M
authors.initials: M
authors.lastname: Da Prada
authors.forename: J R
authors.initials: JR
authors.lastname: Martin
authors.forename: P
authors.initials: P
authors.lastname: Polc
authors.forename: R
authors.initials: R
authors.lastname: Schaffner
authors.forename: R
authors.initials: R
authors.lastname: Scherschlicht
authors.forename: F
authors.initials: F
authors.lastname: Hefti
authors.forename: R K
authors.initials: RK
authors.lastname: Müller
authors.forename: P C
authors.initials: PC
authors.lastname: Wyss
mesh_terms: D012369:2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-hexahydro-3-isobutyl-9,10-dimethoxy- / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D020912:Moclobemide; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D012472:Salivation / Q000187:drug effects; D012895:Sleep, REM / Q000187:drug effects; D013239:Stereotyped Behavior / Q000187:drug effects; D014439:Tyramine / Q000494:pharmacology
chemical_list: D000928:Antidepressive Agents; D001549:Benzamides; D008996:Monoamine Oxidase Inhibitors; D012369:2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-hexahydro-3-isobutyl-9,10-dimethoxy-; D020912:Moclobemide; D014439:Tyramine