Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

On the grounds of different pharmacological properties and possibly different clinical effects, two antidepressants, Anafranil (clomipramine) and Pertofran (desipramine) were compared in the management of depression in general practice. A further comparison was made to ascertain whether a combination of the two antidepressants was more effective than the drugs given alone. One hundred and seventy-three patients were admitted to a double-blind clinical trial, conducted on a multicentre basis in general practice, in which a double-dummy technique was employed. One hundred and forty-one patients completed the study. Of these, 49 received Anafranil, 49 received Pertofran and 43 the combination. Although there were no statistically significant differences between the three treatment regimes, there was a consistent trend in favour of the combination regime. Ninety-one per cent of the patients who completed treatment on the combination showed satisfactory improvement compared with 81% on the Anafranil regime and 78% on Pertofran. An attempt was made to identify three symptom clusters--anxiety, 'anergia' and biological depression. There was no significant difference in the response of these three clusters to the three treatment regimes, nor was there any difference in the incidence and severity of side-effects.
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PMID:A comparative trial of Anafranil, Pertofran and an Anafranil/Pertofran combination. 32 30

Cardiovascular effects of several imipramine analogs were investigated in the anesthetized mongrel dogs. Significant reduction in the cardiac output produced by lower doses (2.5 mg/kg, i.v.) of imipramine and 2-OH-DMI was not due to a depression of myocardial contractility. In contrast, 2-OH-imipramine (1.25 mg/kg) and DMI (2.5 mg/kg) significantly reduced contractility within 10 min after i.v. administration; however, significant decrease in the cardiac output did not occur until after 60 min. Higher doses (5 mg/kg) of imipramine, DMI and 2-OH-DMI significantly attenuated cardiac rate, contractility and output within 5 min after i.v. administration. 2-OH-imipramine, 2.5 mg/kg, i.v., depressed contractility and cardiac output to a degree equivalent to that produced by 5 mg/kg of imipramine, DMI and 2-OH-DMI. 3-Chloro-imipramine (5 mg/kg, i.v.) induced decrease in the cardiac output was essentially due to a significant reduction in the heart rate since the effects of this compound on the contractility were transient in nature. 3-Cl-8-OH-metabolite of this compound had no significant effects on the cardiovascular system. The results of this investigation demonstrated that the complex cardiovascular effects of tricyclic antidepressants observed in these studies were perhaps due to a direct and/or autonomically mediated effects on the heart and vasculature. Further, the data support the conclusions that the activity of the parent compounds together with that of the metabolites contributes to overall changes observed. While all the agents are capable of reducing cardiac output, 2-OH-metabolite of imipramine appears to be most toxic on the myocardium and 3-Cl-imipramine possessed only transient effects on the contractile properties.
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PMID:Effects of several tricyclic antidepressants on the hemodynamics and myocardial contractility of the anesthetized dogs. 85 16

24 depressed impatients received a standardized treatment by imipramine, 6 among them receiving also levomepromazine. Plasma concentration of imipramine and DMI were controlled weekly during the study, and standardized assessment of clinical state were made by a psychiatrist who was unware of biochemical findings. Interaction between the antidepressant and neuroleptic metabolism is shown by a significant increase of DMI levels, though the clinical effect of the drug association could not be asserted. The therapeutic effect seems mainly dependant of etiology of depression. Endogeneous depressions improve more than other types. Among endogenous depressions a significant correlation was found between the degree of clinical improvement after three weeks and DMI level, sum of imipramine + DMI level, but not with concentration of imipramine alone.
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PMID:[Plasma levels of imipramine and desmethylimipramine and antidepressant effect during controlled therapy(author's transl)]. 115 7

The influence of Desmethylimipramin (PertofranR) on the regional uptake of 3H-leucine in different areas of rat brains has been investigated with autoradiographic methods. Male rats were injected 10 m/kg Desmethylimipramin (DMI, PertofranR) i.m. and 1 hr later 8,33 mCi 3H-leucine i.p.. 1 and 7 hrs after application 3H-leucine the animals were sacrificed. Concentrations of silvergrains of 3H-leucine activity were countered under surface illumination in varions brain areas by means of strippingfilmautoradiograms. DMI markedly depressed the concentrations of 3H-leucine-activity in all layers of the parietal cortex after 8 hrs and the depression was greater with the increase of nerv- and gliacellvolumendensity of the layers. Within 2 hrs such an influence of DMI on 3H-leucine uptake could not be found. There was a smaller decrease of 3H-leucine incorporation after DMI applications in some layers of ammon's horn, dentate gyrus and cerebellum. Some further effects of DMI and IP (Imipramine) on components concerned with protein metabolism are discussed.
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PMID:[Autoradiographic studies of the effect of desmethylimipramine (DMI, Pertofran) on the incorporation of 3H-leucine into the rat brain]. 123 14

The drug l-deprenyl has been reported to have antidepressant properties, and in the present study three possible mechanisms of action were investigated in animal experiments. l-Deprenyl, which is a type B monoamine oxidase (MAO) inhibitor, was compared to clorgyline, an MAO A inhibitor with regard to its inhibitory effect on the formation of three major catecholamine metabolites, homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC) and 3-methoxy-4-hydroxyphenylglycol (MOPEG) in the rat brain in vivo. Apart from a difference in dose levels the two drugs showed no difference in the dose--response pattern of all three metabolites. Clorgyline inhibited the formation of HVA, DOPAC and MOPEG with an ED50 of about 0.2 mg/kg s.c. and l-deprenyldopamine and noradrenaline are formed by the same type of monoamine oxidase(s), probably type A, in the rat brain in vivo. Antidepressant properties of l-deprenyl therefore seem to be independent of catecholamine deamination. l-Deprenyl but not clorgyline (2 or 8 mg/kg s.c.) potentiated the stereotyped sniffing behaviour induced by beta-phenylethylamine, a specific substrate for type B monoamine oxidase. This result is discussed in relation to a new hypothesis of phenylethylamine and dopamine involvement in depression. l-Deprenyl was 10,000 times less potent than DMI as inhibitor of noradrenaline uptake in crude synaptosomes from the occipital cortex of rat brain. Inhibition of noradrenaline uptake was therefore excluded as a possible mechanism for the antidepressant action of l-deprenyl.
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PMID:The monoamine oxidase B inhibitor deprenyl potentiates phenylethylamine behaviour in rats without inhibition of catecholamine metabolite formation. 124 62

Depression in feed intake during the final week before calving was hypothesized to be a major factor in the etiology of fatty liver development near parturition. Eleven cows were allowed to eat for ad libitum intake prior to calving (control), and 11 cows were maintained at the same level of DMI recorded during d 21 to 17 prior to calving by force feeding the feed refusals via rumen cannulas. Feed intake by control cows decreased 28% during the final 17 d prior to calving. Lipid triglyceride increased 227 and 75% for control and force-fed cows between d 17 prior to parturition and d 1 following calving. Dry matter intake prior to calving was correlated negatively with liver triglyceride immediately after calving (r = -.80). Plasma glucose concentrations for control and force-fed cows were 63 and 76 mg/dl 2 d prior to calving and also were related closely to liver triglyceride immediately after calving (r = -.50). By d 28 after calving, there were no differences in liver triglyceride between treatments. Cows that were force-fed prior to calving tended to yield milk with greater fat percentage (4.22 vs. 3.88%) and to yield more 3.5% FCM (46.1 vs. 41.7 kg/d) during the first 28 d postpartum.
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PMID:Effect of prepartum dry matter intake on liver triglyceride concentration and early lactation. 150 May 87

A low NDF drought-stressed 1988 alfalfa silage (32.6% NDF) and a higher fiber 1988 alfalfa silage (46.4% NDF) were fed to lactating cows to evaluate effects on feed intake, fat test, and chewing behavior. Two groups of Holstein cows, 16 primiparous housed in tie stalls and 16 multiparous in free stalls, were assigned to diets based on parity and milk yield. The low NDF silage was fed for 6 wk in a TMR with 21.5% NDF and was compared with a TMR with 31.9% NDF. During an additional 4-wk period, one-half of each dietary group was fed a ration in which one-half of each silage was rechopped to reduce particle size. All rations contained a 1:1 ratio of forages to concentrates (DM basis) and were fed for ad libitum intake. Diets with 21.5% NDF and reduced particle size had no influence on milk fat percentage, 4% FCM yield, or plasma glucose. Cows fed these diets had reduced chewing time, due largely to decreased rumination time. Rumination and total chewing times per unit DMI and FCM also were lowest on these diets. Intake of DM on a BW basis was lowest for cows fed the low NDF rechopped silage diet. Cows fed in tie stalls had more eating bouts than those in free stalls, but total eating times were similar. Sufficient amounts of effective fiber appeared to be present in low NDF and rechopped silage diets to prevent the systemic events leading to milk fat depression but not to prevent a reduction in chewing time.
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PMID:Effect of fiber content and particle size of alfalfa silage on performance and chewing behavior. 165 45

The present study reports that long-term (18 days) administration of imipramine (IMI, 20 mg/kg) or desipramine (DMI, 15 mg/kg) produced a significant decrease in the GABA-stimulated 36Cl- uptake into membrane vesicles from the cerebral cortex of rats (experiment 1). Experiments 2A, B show that anti-immobility effects of DMI and IMI (subacute treatment) in the forced swimming test are enhanced when a single subconvulsant injection of picrotoxin or pentylenetetrazol is administered to the animals concurrently to the last antidepressant injection. These results are discussed in relation with a current GABAergic hypothesis of depression and antidepressant drug action.
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PMID:Imipramine and desipramine decrease the GABA-stimulated chloride uptake, and antigabaergic agents enhance their action in the forced swimming test in rats. 196 14

The response to lithium prophylaxis was evaluated in a sample of bipolar patients subdivided into groups, according to the previous pattern of course for their illness: MDI (sequence mania-depression-free interval), DMI (sequence depression-mania-free interval), CC-LC (continuous circular course with long cycles), CC-RC (continuous circular course with rapid cycles), IRR (irregular course). The percentage of responders to treatment was significantly different among the five groups, and the difference could be ascribed mainly to the high response rate in the MDI group and the low response rate in the DMI and CC-RC groups. These data suggest that the classification of bipolar patients on the basis of the previous pattern of their course of illness may be useful for predicting lithium response.
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PMID:Clinical prediction of response to lithium prophylaxis in bipolar patients: the importance of the previous pattern of course of the illness. 211 28

The effects of chronic administration of desimipramine (DMI, 10 mg/kg i.p. daily for 4 or 5 weeks), short-term administration of lithium (Li, 0.2% in food for 10 days) and a combination of these treatments on serotonergic receptors and second messengers were studied in the rat brain. DMI alone had no effect on [3H]5-HT binding but reduced [3H]ketanserin binding in cortical membranes, 5-HT-stimulated inositol phosphate (IP) formation in cortical slices and the degree of inhibition of forskolin-stimulated adenylate cyclase by 5-HT in hippocampal membranes. Li alone reduced [3H]5-HT binding and the degree of inhibition of forskolin-stimulated adenylate cyclase by 5-HT in hippocampal membranes, and also reduced [3H]ketanserin binding and 5-HT-stimulated IP formation in the cortex. The two treatments combined in general produced effects similar to those of Li alone, but the decrease in [3H]ketanserin binding in cortical membranes was significantly greater than that given by Li alone, whereas the reduction in the degree of inhibition of forskolin-stimulated adenylate cyclase by 5-HT in hippocampal membranes was significantly greater than that produced by DMI alone. It is concluded that the therapeutic action of Li when added to tricyclic antidepressants in the treatment of refractory depression may partly have its basis in potentiation of effects on the serotonergic system in the brain.
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PMID:Single and combined effects of desimipramine and lithium on serotonergic receptor number and second messenger function in rat brain. 213 25


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