Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033377 (prolapse)
 11,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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. This finding prompted us to study the effects of minaprine in animal models for depression. Like most antidepressants minaprine antagonizes behavioral despair, but the effect exhibits a slow onset and maximal activity is reached 24 h after administration. Minaprine also antagonizes reserpine-induced ptosis, this effect has a rapid onset, and is long-lasting. In contrast, minaprine poorly antagonizes reserpine-induced hypothermia. Unlike most antidepressants minaprine does not potentiate yohimbine-induced lethality. Minaprine potently antagonizes prochlorperazine-induced catalepsy in rats and potentiates amphetamine-induced stereotyped behavior, suggesting that the drug may enhance dopaminergic transmission. Finally, minaprine does not antagonize either oxotremorine-induced tremors or physiostigmine-induced lethality. Taken together the results of the present study indicate that minaprine is active on certain, but not all, animal models for depression and suggest the drug may have a potential clinical utility in the treatment of human depressions.
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PMID:Pharmacological evaluation of minaprine dihydrochloride, a new psychotropic drug. 689 Mar 59

A series of 4,6-diaryl pyridazin-3-ones substituted in the 2-position by [4-(4-aryl piperazin-1-yl]-but-2-ynyl moieties was synthesized and evaluated for antidepressant activity. The structures of these new pyridazine derivatives were confirmed by IR, 1H-NMR spectra and by elementary analysis. At 150 mg/kg i.p., they induced little or no reduction of the duration of immobility of mice in the forced swimming test. Head twitches produced by L-5-hydroxytryptophan in mice pretreated with pargyline were significantly potentiated by most of the tested compounds. In addition, pyridazine derivatives did not antagonize reserpine-induced palpebral ptosis or enhance the toxic effects of yohimbine and were almost devoid of anticholinergic properties in mice.
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PMID:Synthesis of new serotonergic 2-substituted 4,6-diaryl pyridazin-3-ones. 748 10

The potential antidepressant effects of two pyridazine derivatives, 5-benzyl 6-methyl 2-[4-(3-trifluoro-methyl phenyl) piperazin-1-yl] methylpyridazin-3-one (PC4) and 5-benzyl 6-methyl 2-[4-(3-chlorophenyl) piperazin-1-yl] methylpyridazin-3-one (PC13), were evaluated using classical psychopharmacological tests in mice. The intraperitoneal LD50 values of PC4 and PC13 were respectively 1125.8 and 429.6 mg kg-1. Only at intraperitoneal doses of 100 mg kg-1 did PC4 or PC13 significantly decrease locomotor activity. Both compounds (5-20 mg kg-1, i.p.) reduced the duration of immobility of mice in the forces swimming test, antagonized reserpine (2.5 mg kg-1, i.p.)-induced ptosis, and potentiated reserpine (2.5 mg kg-1, i.p.)-induced hypothermia. PC4 and PC13 (20 mg kg-1, i.p.) partly reversed hypothermia induced by low dose apomorphine (5 mg kg-1, s.c.) but were less effective for higher doses of apomorphine (16 mg kg-1, s.c.). At 200 mg kg-1, intraperitoneal PC13 enhanced the toxic effects of yohimbine (30 mg kg-1, s.c.), while PC4 was inactive. Head twitches produced either by L-5-hydroxytryptophan (4 mg kg-1, i.p.) in mice pretreated with pargyline (100 mg kg-1, i.p.) or by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (3 mg kg-1, i.p.) were antagonized by both pyridazine derivatives (20 mg kg-1, i.p.). PC4 and PC13 showed analgesic properties in the phenylbenzoquinone-induced abdominal constriction test (5.0 < ED50 < 5.5 mg kg-1, i.p.) and in the hot-plate test (10 to 37% of analgesia at 10 mg kg-1, i.p.).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Behavioural profile of two potential antidepressant pyridazine derivatives including arylpiperazinyl moieties in their structure, in mice. 760 73