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)

The effect of the factor that inhibits the release of melanocyte stimulating hormone (MSH), i.e., L-prolyl-L-leucyl-glycinamide (MIF), and L-prolyl-N-methyl-D-leucyl-glycinamide, an analog, on brain norepinephrine (NE), dopamine (DA) and serotonin (5-HT) turnover was examined in rats. The analog (40 mg/kg i.p.), in a fashion similar to MIF (40 and 5 mg/kg i.p.), increased brain DA turnover; only MIF (40 mg/kg i.p.) increased endogenous DA levels. The analog (40 and 5 mg/kg i.p.) decreased brain NE turnover; MIF at the same doses was ineffective. Neither MIF nor the analog affected rat brain 5-HT turnover or the 5-HTP-induced behavioural syndrome in the mouse. These results indicate that the analog, like MIF, exerts effects on central catecholamine turnover. The different biochemical profile of the analog compared to MIF may be importance with regard to potential clinical use in the treatment of Parkinson's disease and depression.
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PMID:Synthetic melanocyte stimulating hormone release-inhibiting factor (MIF). Part III: effect of L-prolyl-N-methyl-D-leucyl-glycinamide and MIF on biogenic amine turnover. 2 96

The influence of serotonergic system on the changes in locomotor activity of mice and rats brought about by morphine, fentanyl, codeine and pentazocine and on morphine induced catalepsy in rats was studied. p-Chlorophenylalanine (pCPA) did not affect the behavioral changes produced in mice by morphine, fentanyl, codeine and pentazocine but reduced the behavioral depression produced by these drugs in rats. 5-Hydroxytryptophan (5-HTP) but not tryptophan (TP) reversed the action of pCPA on the effect of morphine and fentanyl. After reserpine the depression produced in rats by morphine and fentanyl was more pronounced. TP did not change the depression produced by combination of reserpine and morphine but counteracted the depression observed after combination of reserpine and fentanyl. In mice reserpine protected against hypermotility produced by morphine or fentanyl and TP potentiated the depression produced by the combination of reserpine and morphine or reserpine and fentanyl. Serotonin precursors, 5-HTP and TP evidently potentiated the morphine induced catalepsy. pCPA counteracted only the enhancement of the catalepsy observed after TP administration. Naloxone abolished the catalepsy after combined treatment with morphine and TP. Similarly but weaker acted cyproheptadine. The results suggest that the serotonin system plays a role in the effects of morphine and fentanyl on rat locomotor activity. An increase in the cerebral serotonin level increases the morphine catalepsy in rats.
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PMID:Central action of narcotic analgesics. V. Participation of serotonin in the mechanism of action of narcotic analgesics. 4 45

Tryptophan and 5-hydroxytryptophan have now been extensively investigated in affective disorders. There is now very good evidence that tryptophan increases the antidepressant activity of monoamine oxidase inhibitors. The antidepressant activity of tryptophan and 5-hydroxytryptophan has also been the subject of numerous investigations. There is evidence that patients with decreased cerebrospinal fluid concentration of 5-hydroxyindoleacetic acid respond particularly favourably to this treatment. The therapeutic activity of tryptophan has led to the investigation of the plasma concentration of tryptophan. Free plasma tryptophan, that is tryptophan unbound to plasma protein, appears decreased. There is also evidence that tryptophan and 5-HT transported are abnormal in depression.
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PMID:[Indoleamine precursors in depression (author's transl)]. 9 9

Central serotonin (5-hydroxytryptamine; 5-HT) metabolism can be disturbed in a subgroup of patients with vital (endogenous, primary) depression. Presumably these disturbances do not result from the depression and have a predisposing rather than a causative relationship to it. This latter statement is based on two observations. First, in a majority of patients, the 5-HT disturbances persist after depression has abated. Secondly, 5-hydroxytryptophan seems to have prophylactic value, in particular in patients with persistent abnormalities in central 5-HT metabolism. In this study we approached the hypothesis that 5-HT disturbances are a predisposing factor to the occurrence of depression from still another perspective. If this hypothesis is correct, then depressive patients with persistent 5-HT disturbances should have higher frequencies of depression than depressive patients without demonstrable 5-HT disturbances. This was indeed demonstrated. The same was true for family members of probands with low levels of 5-hydroxyindoleacetic acid. No cerebrospinal fluid data are available for family members. The reported findings strongly support the predisposition hypothesis.
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PMID:Central serotonin metabolism and frequency of depression. 9 33

Some recent publications relating to the allegedly antidepressive and sedative effects of L-tryptophan the precursor of 5-HT have been reviewed. The evidence to date suggests that the amino acid is as effective as standard tricyclic drugs in alleviating the symptoms of depression, especially those cases presenting with mainly psychomotor retardation, and is synergistic with MAOIs. L-Tryptophan would also appear to be a 'physiological sedative'. This action, however, appears to be related to the time of administration and at present has only been demonstrated at night. when endogenous levels of 5-HT are at their peak. In terms of practical therapeutics L-tryptophan would appear to have greater potential as an 'antidepressant' than as a 'sedative'.
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PMID:Tryptophan antidepressant 'physiological sedative': fact or fancy? 10 27

Treatment of rats with one electroconvulsive shock (ECS) per day for 10 days enhanced the hyperactivity syndrome produced by administration of tranylcypromine (10 mg kg-1) and L-tryptophan (50 mg kg-1) given 24 h after the final shock. Similar enhancement was seen whether the shock was alternating sinusoidal or direct current (fractionated), whether it was given through unilaterally or bilaterally placed electrodes and whether or not a neuromuscular blocking agent (fazadinium) was used. Five shocks spread over 10 days or 8 shocks spread over 17 days were similarly effective, whilst 8 shocks in 1 day were ineffective. Therefore when ECS are given to rats in ways similar to those in which electroconvulsive therapy is given to patients with depression, enhancement of behavioural responses to increased 5-HT function is produced.
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PMID:Enhanced 5-hydroxytryptamine-mediated behavioural responses in rats following repeated electroconvulsive shock: relevance to the mechanism of the antidepressive effect of electroconvulsive therapy. 10 33

Drugs which increase brain levels of serotonin (5-HT) have frequently been found to cause a decrease in voluntary ethanol consumption. Results obtained with parachlorophenylalanine (pCPA), which decreases 5-HT, have been less consistent. The present investigation compared the effects of pCPA on alcohol selection with those of pargyline, a monoamine oxidase inhibitor which increases brain levels of 5-HT. Ingestion of a 10% ethanol solution was assessed in male C57BL/6J mice given daily injections of 250 or 300 mg/kg pCPA, 50 mg/kg pargyline, or saline. An additional control group received no treatment. A two-bottle preference procedure was employed, and ethanol and water intake were recorded during a pretreatment period (11 days), a treatment period (8 days), and a posttreatment period (10 days). Like other agents which increase 5-HT, parygyline produced a depression in ethanol intake which lasted beyond the time of drug administration. pCPa had no effect on ethanol ingestion either during the period of drug administration or afterwards.
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PMID:Reduction of alcohol selection by pargyline in mice. 13 69

The effect of nomifensine (NF) on the content of serotonin (5-HT) and catecholamines (CA) in discrete regions of rat brain was studied with the histofluorescence technique of Falck, NF, 20 and 40 mg/kg ip, produced, after 30 min, a depression of 5-HT content in the neurocytes of dorsal and median raphe nuclei (NDR and NMR). The blockade of dopamine receptors by spiperone did not abolish the action of NF in NDR, and inhibited the effect in NMR only in some animals. NF did not affect significantly the CA content in the striatum (caudate nucleus--putamen), hypothalamic paraventricular nucleus, and paraventricular rotundocellular nucleus. The results indicate, a direct action of NF on 5-HT neurons in the rat mesencephalon. In addition, the drug may also act indirectly on 5-HT neurons in NMR, via dopaminergic system.
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PMID:Nomifensine and central monoamine neurons: histofluorescence studies. 14 91

Platelets were examined to enable a simultaneous investigation to be made of indolylamine and electrolyte metabolism in affective disorder. No significant differences were detected in either platelet membrane ATPase or adenyl cyclase specific activity in any of the groups of patients studied, when compared with appropriate controls. A reduced Vmax and y for the 5-hydroxy-tryptamine uptake process into platelets was observed in both unipolar and bipolar depressed groups. The Km for this process was not significantly different in any of the patients from that found in control subjects. Lithium therapy was shown not to influence significantly any of the platelet parameters examined. It is suggested that membrane enzyme changes found in some peripheral cells in patients suffering from affective disorder, i.e. reduced Na+ + K+ - ATPase activity in erythrocytes in depression, is not common to all peripheral cells and may or may not reflect central nervous system changes.
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PMID:Studies on human blood platelets in affective disorder. 15 82

The relative abilities of 1--3 mg/kg of desipramine (DES), imipramine (IMIP), amitriptyline (AMI), and chlorimipramine (CI-IMIP) to enhance synaptic transmission mediated by either NE or 5-HT were determined by testing their effects directly on NE or 5-HT transmission to sympathetic preganglionic neurons in unanesthetized, spinal cats. Effects on NE transmission were assessed on intraspinal excitatory pathways which utilize NE as a transmitter. Effects on 5-HT transmission were assessed on 5-HT-mediated depression of spinal sympathetic reflexes produced by 30 mg/kg of 5-HTP. Both DES and IMIP markedly enhanced transmission through the intraspinal excitatory NE pathways whereas AMI and CI-IMIP depressed transmission. However, both AMI and CI-IMIP modestly enhanced transmission in cats depleted of central 5-HT by pretreatment with parachlorophenylalanine. The relative potencies of the four drugs on excitatory NE transmission were DES greater than IMIP greater than AMI greater than CI-IMIP. Each of the four drugs also enhanced the 5-HTP-induced depression of spinal sympathetic reflexes, but their relative potencies on 5-HT transmission were just the opposite to those found on NE transmission. Therefore, all four drugs enhanced transmission by both NE and 5-HT, but their relative selectivities for the two transmitters differed markedly and were complementary. In general, the results support those of previous studies based on less direct methods for assessing inhibition of amine reuptake by tricyclic antidepressants.
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PMID:Enhancement of central norepinephrine and 5-hydroxytryptamine transmission by tricyclic antidepressants. A comparison. 22 Jun 58


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