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In a clinical trial the effect of L-deprenil, a selective irreversible inhibitor of monoamine oxidase (M.A.O.) "type B" in potentiating the anti-kinetic properties of levodopa has been investigated in 223 patients. Both drugs were given orally, levodopa as 'Madopar' (levodopa plus the peripherally acting decarboxylase inhibitor, benserazide) 250 mg three times daily and L-deprenil 5 mg once or twice daily. The addition of L-deprenil to madopar therapy resulted in a statistically significant (P less than 0-01-0-001) reduction in patients' functional disability on average within 60 min after a single oral dose and lasting for 1 to 3 days. Dyskinesia occurred in 16 patients, psychosis in 14, orthostatic hypotension in 5, and nausea in 8. Reduction of the L-deprenil dose to 5 mg in these patients eliminated some of the side-effects. Two-thirds of the patients with side-effects had suffered from parkinsonism for between 7 and 15 years. 14% of the patients failed to respond to madopar-deprenil therapy. It is suggested that L-deprenil may act through inhibition of brain M.A.O. as well as by a psychostimulant effect similar to that of amphetamine which occurs through the release of dopamine. Both mechanisms would make more dopamine available at dopamine receptor sites.
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PMID:Implications of combined treatment with 'Madopar' and L-deprenil in Parkinson's disease. A long-term study. 6 60

Selective serotonin reuptake inhibitors (SSRIs) are a recently developed class of drugs with significantly greater antidepressant efficacy than placebo. Generally, in double-blind comparative trials, all SSRIs demonstrated antidepressant efficacy similar to that of the 'standard' tricyclic antidepressants amitriptyline and imipramine; a meta-analysis of controlled trials found the efficacy of the SSRIs to be equivalent to that of the 2 tricyclics. Nevertheless, because of small patient numbers included in most studies that compare SSRIs with other antidepressants, no definitive statements about relative efficacy can be made. In these studies it is simply possible to state that no statistically significant differences were identified between SSRIs and the comparative antidepressants. Importantly, differences in clinical characteristics exist between the SSRIs-differences in elimination half-life (t1/2 beta) between fluoxetine and/or its metabolite (total t1/2 beta = 330 hours) and other SSRIs (t1/2 beta range = 15 to 30 hours), for example. This has implications in terms of potential drug interactions and must be considered when patients have to be switched to treatment with monoamine oxidase inhibitors. Studies with fluvoxamine have been conducted in both in- and outpatients, whereas trials with other SSRIs have been confined largely to outpatient populations. Fluvoxamine has been associated with a high incidence of nausea (37%), although this may have resulted from high initial dosages (rather than upward dose titration protocols) used in early trials. Of further interest, fluoxetine doses of 20mg may be sufficient to produce a satisfactory antidepressant response, and this SSRI may be particularly useful in patients with chronic retarded depression. More clinical data are required before the efficacy of sertraline and citalopram relative to standard antidepressants can be clearly defined. Preliminary data indicate that SSRIs are effective in the treatment of panic disorder, obsessive-compulsive disorder (OCD), eating (e.g. anorexia and bulimia) and personality disorders (e.g. anger, impulsiveness) and substance abuse (e.g. alcoholism); early results with fluvoxamine in the treatment of panic disorder and OCD, and with fluoxetine in the treatment of bulimia, personality disorders and alcohol abuse, have been encouraging. SSRIs have a more favourable tolerability profile than tricyclic antidepressants and, unlike the tricyclics, are not associated with anticholinergic adverse effects, sedation, cardiotoxicity or weight gain. SSRIs are associated with a relatively high incidence of nausea, particularly if high doses are used at the start of treatment. However, the incidence of nausea appears to decrease as treatment is continued.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Comparative efficacy of antidepressants. 137 69

Side effects remain one of the most important clinical issues in antidepressant therapy. Patients may not be able to take appropriate treatment or may not tolerate their medication in adequate doses or for an adequate length of time to manage their depressive illness. This article reviews the extensive safety data from 6705 patients treated with paroxetine. These data indicate that paroxetine has no significant cardiovascular effects, few significant drug interactions, and no clinically significant effects on the ECG or EEG. Furthermore, paroxetine is relatively safe in overdose and has very little anticholinergic activity. Psychomotor performance is not impaired by paroxetine and there is no evidence of any zimelidine-like hypersensitivity reactions or increase in suicidal ideation. As with other selective serotonin reuptake inhibitors (SSRIs), the most common side effect is gastrointestinal upset, especially nausea. This is usually very well tolerated and rarely leads to drug discontinuation. As with other SSRIs, monoamine oxidase inhibitors should not be prescribed concurrently or soon after discontinuing paroxetine because of the risk of a lethal interaction. Paroxetine may be less likely than currently available SSRIs to cause agitation. In general, paroxetine has a very favorable side effect profile and should be an important alternative in the medical treatment of depressive illness.
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PMID:The safety profile of paroxetine. 153 28

Deprenyl is a synthetic, selective inhibitor of the monoamine oxidase-B enzyme system. The mechanism of its beneficial effect in early and advanced Parkinson's disease is not settled. Increased striatal dopamine accumulation, sensitization of surviving dopamine neurons with increased dopamine production and reduced nigro-striatal toxicity may all contribute. The standard daily dose of deprenyl is 10 mg. Selectivity may be lost at higher doses. Deprenyl is especially indicated in untreated patients, improving up to 50 percent of patients with mild motor fluctuations. Major symptomatic benefit also occurs in occasional levodopa treated patients. Adverse effects are common, however. Increase dyskinesias, confusion and hallucinations, nausea and postural hypotension may necessitate drug withdrawal or the use of low dose regimens. Caution should be exercised with older patients, those with ulcer disease, which may be worsened by deprenyl, and individuals with active ischemic heart disease where the safety of this drug is not yet clear.
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PMID:Deprenyl in Parkinson's disease: mechanisms, neuroprotective effect, indications and adverse effects. 157 60

A review of the clinical efficacy of four structurally distinct antidepressant drugs is presented. Their antidepressant activity can be rationalised within current pharmacological hypotheses of drug action, despite markedly different effects on "in vitro" testing. Fluoxetine, a specific serotonin re-uptake inhibitor, has proven safe, effective treatment for depressive illness and may have a role to play in the treatment of obsessive-compulsive disorder and panic attacks. While it has few of the anticholinergic side effects of the tricyclic antidepressants, nausea, tremor, headache, weight loss, nervousness and sweating are side effects most frequently reported. Minaprine, a compound with weak MAO inhibiting properties and effects on serotonergic receptors, has clinical efficacy in the treatment of depression based on several comparative studies. It is claimed that minaprine lacks anticholinergic and sedative properties. Moclobemide, a specific, reversible inhibitor of MAO-A, has been extensively evaluated in depressive illness. The major advantage of this agent over other irreversible, non-specific MAO inhibitors, is the significant attenuation of the so-called "cheese effect" with doses of tyramine likely to be encountered in foodstuffs. Rolipram, a phosphodiesterase inhibitor, represents a new approach to antidepressant treatment. Limited clinical data suggest that the drug may be an effective antidepressant with few side effects. The place of these agents in therapy is yet to be established.
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PMID:New pharmacological approaches to the management of depression: from theory to clinical practice. 158 Aug 88

1. The authors review the literature describing acute symptomatology produced by the gradual or abrupt withdrawal of heterocyclic antidepressants, monoamine oxidase inhibitors (MAOI) and neuroleptics. 2. Withdrawal of heterocyclic antidepressants and antipsychotic agents causes similar symptomatology. Symptoms produced by the discontinuation of these drugs include nausea, emesis, anorexia, diarrhea, rhinorrhea, diaphoresis, myalgias, paresthesias, anxiety, agitation, restlessness, and insomnia. 3. Psychotic relapse is often presaged by anxiety, agitation, restlessness, and insomnia. Prodromal symptoms are distinguished from the effects of neuroleptic withdrawal by a temporal relationship of the latter to reductions in the dosage or discontinuation of antipsychotic agents. 4. Withdrawal of MAOIs can result in severe anxiety, agitation, pressured speech, sleeplessness or drowsiness, hallucinations, delirium, and paranoid psychosis. 5. MAOI withdrawal phenomena resemble the symptoms produced by the discontinuation of chronically administered psychostimulants. 6. The capacity of MAOIs to exert amphetamine-like effects presynaptically and the propensity of somatic treatments for depression to subsensitize presynaptic receptors regulating the release of catecholamines provide a basis for the development of psychotic symptoms upon the withdrawal of MAOI. Evidence for this hypothesis is reviewed.
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PMID:Heterocyclic antidepressant, monoamine oxidase inhibitor and neuroleptic withdrawal phenomena. 196 71

The chemistry, pharmacology, pharmacokinetics, adverse effects, and dosage of clomipramine hydrochloride are described, and clinical studies of the use of clomipramine in treating obsessive-compulsive disorder (OCD), other psychiatric conditions, and chronic pain are reviewed. Clomipramine hydrochloride, a tricyclic antidepressant, is a potent inhibitor of serotonin reuptake and may affect dopaminergic neurotransmission, suppress rapid eye movement sleep, produce changes in electrocardiograms, and elevate plasma prolactin. The drug is well absorbed from the gastrointestinal tract and undergoes extensive first-pass metabolism. Peak plasma concentrations occur three to four hours after a 150-mg oral dose. The mean elimination half-life is 39 hours. Some 66% of a dose is excreted in the urine, the remainder being eliminated in the feces. In clinical trials, clomipramine was significantly more effective than placebo, clorgiline, amitriptyline, imipramine, and doxepin in ameliorating the symptoms of OCD. Initial effects are seen at four weeks; improvement may continue for up to 18 weeks. Clomipramine may also be effective in treating panic attacks, phobias, depression, and chronic pain. The most common adverse effects of clomipramine are anticholinergic; others include nausea, seizures, and sexual difficulties. Interactions between clomipramine and barbiturates, haloperidol, monoamine oxidase inhibitors, and cigarette smoking have been documented. The usual initial adult dosage is 25-50 mg/day, titrated gradually to 250 mg/day if necessary. Clomipramine hydrochloride is a welcome new agent for the treatment of obsessive-compulsive disorder. Although its adverse-effect profile is like that of other tricyclic antidepressants, sexual dysfunction and seizures may be more frequent with this agent and limit its use.
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PMID:Clomipramine: an antiobsessional tricyclic antidepressant. 218 Jun 23

Deferoxamine treatment may produce serious side effects that can be eliminated by modification of treatment and by control of deferoxamine metabolism. A patient suffering from dementia of the Alzheimer type with normal liver and kidney function who was treated with deferoxamine initially tolerated a dose of 7 mg/kg deferoxamine mesylate injected intramuscularly twice a day for a total of 5 days a week. After several months nausea and weight loss gradually developed in the patient that could be controlled initially by dose reduction, leading to levels inappropriate for aluminum chelation. HPLC analysis of blood and urine revealed several metabolites including, as a major component, a plasma monoamine oxidase (MAO) catalyzed end product MFO1. Coadministration of isoniazid, a plasma MAO inhibitor, with deferoxamine resulted in reduction of MFO1 from 81% to 8% accompanied by increases in the amounts of metabolite 2 (MFO2) from 2% to 24% and unmetabolized deferoxamine from 17% to 68% after 6 months of treatment. The side effects subsided, the patient regained weight, and treatment could be continued.
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PMID:Suppression of deferoxamine mesylate treatment-induced side effects by coadministration of isoniazid in a patient with Alzheimer's disease subject to aluminum removal by ionspecific chelation. 222 4

As most diet therapy texts provide little information about psychiatric illnesses and their treatment, this article is intended as a brief introduction for dietitians. Several psychiatric illnesses, including schizophrenia, mood disorders, eating disorders, and substance abuse, may adversely affect food intake and nutritional status. The drugs used to treat those disorders similarly have effects on appetite and gastrointestinal function and interact with food and nutrients. Antipsychotics, antidepressants, and monoamine oxidase inhibitors (MAOIs) cause dry mouth, constipation, and weight gain. Lithium may cause nausea, vomiting, diarrhea, polydipsia, and weight gain. MAOIs have well-known interactions with foods containing tyramine. Lithium interacts with dietary sodium and caffeine; decreasing dietary intakes of those substances may produce lithium toxicity. Despite claims to the contrary, major psychiatric illnesses cannot be cured by nutritional therapies alone. Dietitians can, however, play an important role as part of a multidisciplinary team in the treatment of patients with psychiatric illness. Such a role includes nutrition assessment and monitoring, nutrition interventions, patient and staff education, and some forms of psychotherapy, including supportive and behavioral therapies for patients with eating disorders.
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PMID:Nutritional aspects of psychiatric disorders. 267 98

Moclobemide is a reversible monoamine oxidase inhibitor (MAOI) which preferentially inhibits type-A MAO. In the present communication the results obtained with moclobemide in various clinical trials are reviewed. To this day, the antidepressant efficacy of moclobemide has been compared to that of placebo in four trials. The antidepressant efficacy of moclobemide (300-600 mg/d; N = 164) was found to be superior to that of placebo (N = 162) and comparable to that of imipramine (100-200 mg/d; N = 164) in a 6-w., double-blind, multicentre study, in patients suffering from a Major Depressive Episode (DSM-III). Two smaller trials, strongly suggest that moclobemide is more efficacious than placebo for the treatment of endogenous depression (ICD-9) and for the treatment of Dysthymic Disorders (DSM-III). The antidepressant efficacy of moclobemide was compared to that of imipramine, desipramine, clomipramine and amitriptyline. The antidepressant efficacy of moclobemide (300-600 mg/d; N = 189) was found to be comparable to that of imipramine (100-200 mg/d; N = 192) in a 4-w., double-blind, multicentre study, in patients suffering from a Major Depressive Episode. This finding is supported by the results obtained in 12 other smaller studies, using either imipramine, desipramine, clomipramine or amitriptyline as comparator drug. When the tolerability of moclobemide, as judged by reported and observed adverse events, is compared to that of placebo, it appears that only nausea is reported significantly more frequently with moclobemide than with placebo (9.5% vs 4.8%). In the trials comparing moclobemide to tricyclic antidepressant drugs (TCAs), the tolerability of moclobemide was constantly found to be superior to that of the TCAs; in particular the incidence of anticholinergic side effects was low with moclobemide and was significantly higher with the TCAs. The cardiovascular tolerability of moclobemide tended to be superior to that of the TCAs. Physical examination, hematology and clinical chemistry did not seem to be affected by treatment in any of the studies summarized in this review.
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PMID:Review of comparative clinical trials. Moclobemide vs tricyclic antidepressants and vs placebo in depressive states. 267 44


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