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)

We have examined the effects of two monoamine oxidase (MAO) inhibitors with different mechanisms of action--phenelzine and brofaromine--on peripheral serotonergic (5-hydroxytryptamine [5-HT]) measures, sensitive to the inhibition of MAO-A (intra- and extracellular 5-HT and related metabolites in blood). Both drugs increased the concentration of 5-HT in platelet-free plasma (254%, p less than 0.001) in patients with depressive illness (DSM-III-R) after 6 weeks of daily treatment. Platelet 5-HT was also increased significantly in both drug treatment groups but more marked in the patient group treated with phenelzine. The acid/amine ratio at 6 weeks was 30% of pretreatment values (p less than 0.000) and individual variability correlated significantly with the Hamilton Rating Scale for Depression. Plasma 5-HT increased more markedly in responders than in nonresponders and a significant inverse relationship surfaced between plasma 5-HT and the Hamilton Rating Scale for Depression. The results support other reports of comparable antidepressant efficacy for brofaromine and phenelzine, both inhibitors of MAO-A in humans. The consistent relationship we found between the biochemical and clinical changes again suggests and supports a key role of 5-HT in the antidepressant effect of these MAO inhibitors.
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PMID:Monoamine oxidase inhibitors phenelzine and brofaromine increase plasma serotonin and decrease 5-hydroxyindoleacetic acid in patients with major depression: relationship to clinical improvement. 128 22

The effects of 5-hydroxytryptamine (5-HT; given i.p. in doses of 1 or 10 mg/kg) on gastric secretion and mucosal blood flow (GMBF) and on ethanol-induced gastric mucosal damage were studied in rats over a period of 30-450 min. The blood pressure was also examined, in relation to the changes in GMBF. 5-HT, 10 mg/kg, given 30 min before ethanol administration markedly worsened lesion formation and this potentiating action was present for a further 90 min; a significant protective effect was seen only at 450 min after 5-HT injection. The lower dose of 5-HT, 1 mg/kg, did not affect the severity of gastric damage. 5-HT (10 mg/kg) also decreased GMBF at 30 min after injection and this lasted up to the end of 120 min, but the depressive action of ethanol on GMBF was reversed at 450 min. The basal gastric secretory volume was depressed from 30 to 120 min but acid output fell from 75 to 120 min after the higher dose of 5-HT; this reduction of acid secretion was followed by an increase from 360 to 450 min. 5-HT decreased the mean blood pressure in a dose- and time-dependent manner. The heart rate was unaffected by either dose level of 5-HT. The present study not only demonstrates the ulcerogenic action of 5-HT but also the protective nature of the amine. The reduction in secretory volume and lesion formation, but not acid secretion, seems to be related to GMBF depression, whereas the protective action depends on the maintenance of GMBF.
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PMID:Time course study on the action of 5-hydroxytryptamine on gastric secretion and mucosal blood flow and on ethanol-induced gastric mucosal damage in rats. 128 76

Platelet 14C-5-hydroxytryptamine (14C-5-HT) uptake, 3H-imipramine binding and monoamine oxidase (MAO) activity were measured in women 5 days postpartum and compared with depression scores (Edinburgh Postnatal Depression Scale) at that time and 6 weeks later. Mean Km of 14C-5-HT uptake was significantly reduced in the group showing dysphoria at 5 days (p less than 0.01). Mean Kd of 3H-imipramine binding was significantly increased in the group who later went on to become depressed at 6 weeks postpartum (p less than 0.03). Vmax for 14C-5-HT uptake, Bmax for 3H-imipramine binding and MAO activity did not differ between depressed and non-depressed patients on either occasion. Although the observed changes manifested in a system known to be disturbed in other forms of depression, they were in affinity rather than Bmax or Vmax. Even though probably not of direct physiological significance, such results, if confirmed, together with other pointers in the literature, suggest biochemical abnormalities specific to the puerperal period.
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PMID:Abnormal platelet 5-hydroxytryptamine uptake and imipramine binding in postnatal dysphoria. 131 74

We electromagnetically measured blood flow to one cerebral hemisphere and determined cerebrovascular reactivity to vasoconstrictor and vasodilator stimuli during normoglycemia and insulin-induced hypoglycemia in unanesthetized goats. Control blood glucose concentration was 84 +/- 4 mg, and insulin, injected intravenously, decreased glycemia with a concomitant increment in cerebral blood flow and reduction in cerebrovascular resistance in all the animals. When glycemia decreased to 60 to 65 mg/dl, the animals began to show signs of increased adrenergic activity, and when it decreased to less than 30 mg/dl, they showed signs of CNS depression. Cerebral blood flow began to rise significantly at a glycemia of 50 to 55 mg/dl, and progressively increased to reach an increment of 36% +/- 4% when glycemia was less than 30 mg/dl. Norepinephrine (0.3 to 9 micrograms), tyramine (50 to 500 micrograms), and 5-hydroxytryptamine (0.1 to 9 micrograms) reduced cerebral blood flow, and this effect was lower during severe hypoglycemia. Acetylcholine (0.01 to 1 microgram), isoproterenol (0.03 to 3 micrograms), diazoxide (0.3 to 9 mg), and inhalation of 10% CO2 in air increased cerebral blood flow, and this effect was also lower during severe hypoglycemia. The results show that insulin-induced hypoglycemia causes cerebral vasodilation and reduction of the capacity of cerebral blood vessels to constrict and dilate. They also show that the glycemic thresholds for increasing cerebral blood flow are near to, or slightly lower than, the thresholds for hypoglycemic symptoms. This experimental model of hypoglycemia closely resembles the conditions in hypoglycemic patients and permits serial evaluation of the cerebrovascular effects of hypoglycemia without using anesthesia.
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PMID:Effects of hypoglycemia on the cerebral circulation in awake goats. 131 45

That the 'primary' phenomenon in migraine with aura is neuronal ('spreading depression') seems increasingly probable, but the relationship of migraine with and without aura and of both to tension headache remains uncertain. Depression and migraine are related, but other psychological correlates are controversial. Two new therapeutic agents, with action on 5-hydroxytryptamine (5-HT; serotonin) receptors are of promise.
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PMID:Headache and migraine. 132 Apr 35

Developed for the treatment of migraine, sumatriptan is an agonist of 5-hydroxytryptamine-1-receptors. Though a pressure sensation is a common complaint, significant ECG changes have not been reported after subcutaneous administration of sumatriptan. A case history is given where angina pectoris after sumatriptan self-administration was experienced on two occasions by a 61-year old man with a history of minor myocardial infarction--without post-infarction angina--two years previously. The angina after sumatriptan was accompanied on both occasions by significant ST-segment depression on ECG-monitoring. An extracranial vasoconstrictor action of sumatriptan in patients with ischaemic heart disease is suggested.
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PMID:[Angina pectoris after sumatriptan (Imigran)]. 133 86

Depression is associated with a risk of suicide 13 to 30 times greater than in the general population, and antidepressants are among the drugs most frequently implicated in fatal overdose, resulting in a dilemma for the clinician. Suicidal thoughts are a core symptom of depression, and there is evidence that the selective serotonin (5-hydroxytryptamine) reuptake inhibitors (SSRIs), including fluvoxamine, are of particular benefit in reducing their occurrence. Data from controlled studies indicate that the SSRIs do not exacerbate suicidal ideation; on the contrary, SSRIs protect against the emergence of suicidal thoughts, which reflect the natural history of the disease. The SSRIs also appear to be particularly effective in patients who are highly suicidal at treatment initiation, and to be more effective than the tricyclic antidepressants in treating severe depression and improving anxiety symptoms associated with depression. Thus, fluvoxamine, in common with other SSRIs, is of particular benefit in treating depression in patients with prominent suicidal thoughts or who are at increased risk of suicide.
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PMID:Suicide and antidepressants. 137 70

Depression is a heterogeneous disease state characterised by complex alterations in several CNS neurotransmitter and receptor systems. All antidepressants are thought to act by causing postsynaptic adaptive changes (e.g. in transducers or second messengers) within these systems. Thus, the mechanism of action of selective serotonin reuptake inhibitors (SSRIs) cannot simply be explained in terms of inhibition of serotonin (5-hydroxytryptamine) [5-HT] reuptake. Fluvoxamine, sertraline and fluoxetine downregulate central beta-adrenoceptors, and all SSRIs are believed to normalise central 5-HT1A- and 5-HT2-receptor density and function in patients with depression. SSRIs are as effective as tricyclic antidepressants in the treatment of depression, but have distinct tolerability advantages--they are not associated with anticholinergic adverse effects, cardiotoxicity, sedation or weight gain. However, gastrointestinal reactions (e.g. nausea, diarrhoea/loose stools, constipation) are relatively common during SSRI therapy. Additionally, in contrast to tricyclic antidepressants, SSRI dosage adjustments appear to be unnecessary in elderly depressed patients. Fluvoxamine has a much shorter elimination half-life than fluoxetine and its active metabolite, norfluoxetine, and therefore a reduced potential for drug interactions. Only small amounts of fluvoxamine and fluoxetine, but large quantities of paroxetine, are secreted in breast milk. Furthermore, genetic polymorphism has not been documented for fluvoxamine metabolism, whereas slow and fast metabolisers of paroxetine, and fast metabolisers of fluoxetine have been identified. SSRIs have a better tolerability profile than tricyclic antidepressants, as indicated by lower mean rank scores for behavioural toxicity. Moreover, SSRIs are associated with a much lower incidence of fatal toxicity than tricyclics, and appear to be relatively safe in overdosage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacological differences of serotonin reuptake inhibitors and possible clinical relevance. 137 71

Phenelzine (PLZ), a nonselective monoamine oxidase inhibitor, is widely used in psychiatry for the treatment of panic disorder and depression. The effects of chronic (28-day) administration of PLZ (0.05 mmol/kg/day) and its N-acetylated analogue, 1-acetyl-2-(2-phenylethyl) hydrazine (N2-acetylphenelzine; N2AcPLZ; 0.10 mmol/kg/day), on alpha 2-adrenoreceptor function were investigated by use of a behavioral test on days 21 and 22. Rats treated with PLZ or N2AcPLZ displayed a significant attenuation of the suppressant effects of clonidine on spontaneous locomotor activity, compared with controls; these results suggest a reduced sensitivity of alpha 2-adrenoreceptors. By day 28, both PLZ and N2AcPLZ had produced greater than 85% inhibition of monoamine oxidases A and B in the brain, heart, and liver. Both drugs induced significant elevations of whole-brain levels of noradrenaline, 5-hydroxytryptamine, and dopamine, compared with those in controls. The levels of acid metabolites of dopamine and 5-hydroxytryptamine (homovanillic acid, 3,4-dihydroxyphenylacetic acid, and 5-hydroxyindole-3-acetic acid) were significantly reduced in both groups of drug-treated animals.
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PMID:Chronic administration of the antidepressant-antipanic drug phenelzine and its N-acetylated analogue: effects on monoamine oxidase, biogenic amines, and alpha 2-adrenoreceptor function. 138 93

Ondansetron (GR 38032) has potent and highly selective antagonist properties at the 5-hydroxytryptamine (5-HT, serotonin) 5-HT3 receptor. The selectivity ratio for ondansetron on 5-HT3 receptors compared with actions on other neurotransmitter receptor types is greater than 1,000. The antiemetic properties of ondansetron have been determined in ferrets against the nausea and vomiting induced by cisplatin, cyclophosphamide, and whole-body radiation. Ondansetron (intravenous 0.01 to 0.1 mg/kg or subcutaneous 0.1 to 0.5 mg/kg) or metoclopramide (1.0 to 4.0 mg/kg) cause dose-dependent inhibitions of the vomiting induced by each of these procedures. Unlike ondansetron, the effects of metoclopramide are accompanied by moderate to marked behavioral depression. Since metoclopramide is 50 times more potent on dopamine D2 receptors than on 5-HT3 receptors, the behavioral depression is likely due to profound blockade of dopamine receptors. The 5-HT3 receptors have been shown to be present peripherally on vagal afferent fibers and are densely located in the vomiting center of the hindbrain. The current hypothesis is that there may be both a peripheral and a central site of action for ondansetron and other 5-HT3 antagonists. The lack of antagonist activity on dopamine and other non-5-HT3 receptors indicates that, unlike metoclopramide, ondansetron will not cause extrapyramidal or other dose-limiting side effects.
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PMID:Pharmacology and preclinical antiemetic properties of ondansetron. 138 45


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