minaprine

Subchronic (5 mg/kg daily for 9 consecutive days) but not acute minaprine treatment enhanced in vivo dopamine release in the limbic part of the striatum of rats as revealed by intracerebral microdialysis. Moreover, the same subchronic treatment with minaprine reduced immobility in the forced swimming test. The anti-immobility effect of minaprine was not evident after a single injection of the antidepressant. Finally, the subchronic treatment with minaprine was devoid of effects in an activity test. These results suggest that enhanced dopaminergic transmission may contribute to the pharmacological and clinical profile of this drug...

Involvement of protein kinase C (PKC) activation in the regulation of acetylcholine (ACh) release from rat hippocampal slices by minaprine, [3(2-morpholinoethylamino)-4-methyl-6-phenylpyridazine] was investigated. Phorbol esters such as 4 beta-phorbol 12,13-dibutylate (PDBu) and 12-o-tetradecanoylphorbol 13-acetate (TPA) enhanced high K(+)-evoked [3H]ACh release from rat hippocampal slices. The enhancing effect of phorbol ester was attenuated by PKC inhibitors, staurosporine and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7)...

Post-training administration of minaprine (2.5, 5 and 10 mg/kg) dose-dependently improved retention of an inhibitory avoidance response in mice. Animals receiving nine daily injections of 5 mg/kg and administered a challenge dose post-training showed an improvement in memory consolidation similar to that produced by acute injection of 10 mg/kg. The effects on retention performance induced by the drug appear to be due to an effect on memory consolidation. They were observed when drugs were given at short, but not long, periods of time after training, i...

This study examines the effect of the psychotropic drug minaprine on memory impairment in Mongolian gerbils subjected to a 5-min bilateral common carotid artery occlusion, as assessed by their performance in an 8-arm radial maze task. Gerbils were initially trained on the 8-arm radial maze until their mean error was 0-1 for 5 days. This task was repeated before the ischemia was performed and again 7 days after it. Then the animals were immediately sacrificed for histopathological examination. Severe memory impairment occurred in the control gerbils; whereas when minaprine 75 mg/kg was given orally 30 min before the 5-min occlusion, memory impairment was significantly reduced...

This multicentre study compares the therapeutic efficacy and safety of minaprine (200 mg) to that of imipramine (50, 75, 100 mg) in the treatment of patients over 40 years suffering from dysthymic disorders as diagnosed according to DSM III. After 4-7 days on placebo, 67 patients were randomly assigned to receive either drug for a period of 6 weeks in a double-blind manner. As rated by the Hamilton Depression Rating Scale and evaluated by exploratory statistics, minaprine showed similar efficacy to imipramine in these patients...

The tricyclic antidepressant desipramine impaired shuttle-box avoidance acquisition in mice of the CD-1 strain. The nootropic drug oxiracetam was unable to prevent the desipramine-induced learning impairment, while a protective action was exerted by minaprine, a psychotropic agent regarded as an atypical antidepressant drug, possessing dopaminergic and related memory-enhancing properties. It seems likely that the dopaminergic action of minaprine played a determinant role in its avoidance improving effects in desipramine treated mice, because similar effects were produced by amphetamine...

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A double-blind, crossover trial was carried out in 26 children with psychiatric disorders to assess the effectiveness of treatment with minaprine (100 mg per day) or placebo, each treatment being given in random order for 4 weeks. Patients were assessed before treatment and at 14 day intervals using a modified 34-item Hamilton rating scale. The results showed a definite therapeutic superiority of minaprine over placebo and a good response was achieved in over 50% of the children, including those showing signs of the "hyperactive syndrome'...

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Minaprine (3-[2-morpholino-ethlamino]-4-methyl-6-phenyl-pyridazine dihydrochloride; 30038CM; trade name in France: Cantor) is a new psychotropic drug. The therapeutic profile of minaprine differs from that of other known psychotropic agents; in man the drug antagonizes the "inhibitory syndrome" characterized by decreased spontaneous activity, reduction in basic drives, slowed thoughts, feelings of tiredness and social withdrawal. Preliminary clinical trials have indicated that minaprine may also be effective in certain depressive states...

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A simple and rapid high-performance liquid chromatographic method is described for the quantitative analysis of the psychotropic drug minaprine and three of its metabolites (M1, M3 and M11), including one as yet undetected metabolite (M11) known as a monoamine oxidase type A inhibitor in vitro. After selective extraction all four compounds were separated on a reversed-phase muBondapak C18 column using sodium acetate (0.03 M)-acetonitrile-methanol (88:7:5) (pH 3.3) as the mobile phase. The eluted compounds were detected with a UV detector at 254 nm...

1. [14C]Minaprine was administered as a single oral dose to five animal species and to a healthy and informed volunteer. Excretion of radioactivity was followed during 48 h in urine and faces; biliary excretion was followed only in rat. 2. Urinary metabolites were isolated and identified by mass spectrometry. 3. A quantitative comparison of metabolites in different species was made. On the basis of these data it it concluded that the dog is not a suitable model for man for pharmacological or toxicological studies...

3-(2- morpholinoethylamino )-4-methyl-6-phenyl pyridazine dihydrochloride (minaprine), has recognized clinical activity against inhibition of action. In rats, this substance antagonizes the increase of plasma corticosterone levels caused by physostigmine injection. The mechanism of this action is discussed.