Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tricyclic antidepressants (TCAs) are notorious for a number of disadvantages, but particularly for an array of side-effects that leads to poor compliance, and also for a dangerous toxicity in overdose. Lofepramine is a new tricyclic that seems safer. Selective serotonin reuptake inhibitors (SSRIs) are more limited in their actions. Side-effects include nausea and insomnia, but on the whole the side-effect profile is an improvement on the TCAs. A miscellaneous group of novel antidepressants includes mianserin and trazodone (which both produce drowsiness) and viloxazine (which causes nausea). The reversible inhibitors of monoamine oxidase A (RIMAs) are a group of drugs that, by producing inhibition selectively of monoamine oxidase A (MOA-A), still allow metabolism of tyramine by MAO-B. Moclobemide is a RIMA that has proved itself to be very effective in severe depressive illness. It is remarkably safe and has an exceptionally low incidence of side-effects. It may be expected to be associated with a high acceptability in depressed patients.
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PMID:Recent advances in antidepressant drugs. 160 37

Both the catechol-O-methyltransferase (COMT) inhibitor entacapone and the monoamine oxidase B (MAO-B) inhibitor selegiline are L-dopa extenders. Both are used, often simultaneously, as adjuncts to L-dopa/dopa decarboxylase (DDC) inhibitor treatment of Parkinson's disease (PD). Their possible interactions have not been previously studied in a double-blind manner.We studied clinical response, tolerability, haemodynamics and cardiac rhythm in 16 PD patients with end-of-dose-type motor fluctuations. The patients' individual L-dopa/DDC inhibitor treatment was stabilized before the experimental treatments. This was followed by three consecutive, randomized, double-blind 2-week treatment periods with entacapone (200mg with each L-dopa dose), selegiline (10mg o.d.) or both entacapone and selegiline with the L-dopa/DDC inhibitor medication. Clinical efficacy (L-dopa test with repeated motor and dyskinesia scoring) and safety (orthostatic test, 24-h ambulatory ECG, haematological and clinical chemistry variables and adverse events) evaluations were performed before each treatment (control) and at the end of each treatment period.All three treatments, entacapone, selegiline, and entacapone+selegiline as adjunct to L-dopa/DDC inhibitor improved (p<0.05) clinical disability compared to L-dopa only but they did not differ significantly from each other. Dyskinesias increased with all the treatments, statistically significantly (p<0.01) with entacapone+selegiline. No significant differences in haemodynamics were observed between control and any of the experimental treatments, or between the experimental treatments in the orthostatic test. One patient already had symptomatic orthostatism before experimental treatments (control). In two other patients orthostatism emerged after the introduction of selegiline, and in one after every experimental treatment. Twenty-four-hour ECG did not show any differences in supraventricular or ventricular extrasystoles or heart rate between treatments. No statistically significant differences were observed in adverse events or in haematology and clinical chemistry variables. One patient treated with entacapone+selegiline discontinued the study due to dizziness and insomnia. Our results suggest that co-administration of entacapone with L-dopa/DDC inhibitor, with or without selegiline, improves clinical disability, is safe, but may also enhance dopamine-related adverse events to some extent in PD patients with end-of-dose type motor fluctuations.
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PMID:Entacapone and selegiline with L-dopa in patients with Parkinson's disease: an interaction study. 1090 Mar 96

(-)-Deprenyl (selegiline) is an irreversible inhibitor of monoamine oxidase (MAO) B, which was discovered in 1962 and become the "golden standard" of MAO research. Like the other MAO-B inhibitors, it was synthesized as an antidepressant, but in a selective MAO-B inhibitory dose it does not act in depression. It is used in the treatment of Parkinson's disease. (-)-Deprenyl potentiates the effect of dopamine, it has antioxidant activity and prevents the toxicity of the dopaminergic (6-OH-dopamine; 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP)), the noradrenergic (DSP-4) and cholinergic (AF64A) neurotoxins after pre-treatment. When (-)-deprenyl was administered with levodopa in a long-term treatment of Parkinsonian patients, it induces adverse events (nausea, dizziness, confusion, hallucination, insomnia and cardiovascular changes), which could be due to dopamine potentiation in dopaminergic systems (limbic system), other than the nigrostriatal pathway. (-)-Deprenyl in much lower concentrations needed to induce MAO-B inhibition (10(-9) to 10(-13) M) potently inhibits MPTP or serum withdrawal induced apoptosis in tissue cultures of neuro-ectodermal origin (PC12, M1, M2058). The (+)-enantiomer of deprenyl lacks of this property. The anti-apoptotic activity of (-)-deprenyl can be prevented by inhibiting the metabolism of the drug with SKF-525A pre-treatment, which suggests that some of the presently unknown metabolites could be responsible for the anti-apoptotic activity. In high concentration (10(-3) M), (-)-deprenyl and its metabolites induce apoptosis in tissue cultures without serum withdrawal (biphasic action). Our findings support the view that 100, or even 1000 times lower dose of (-)-deprenyl can be offered in human therapy to protect, or slow down neuronal degeneration, than it is presently used. With low dose of the drug the dopaminergic adverse events could be avoided, while anti-apoptotic activity might be preserved.
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PMID:(-)-Deprenyl, a selective MAO-B inhibitor, with apoptotic and anti-apoptotic properties. 1469 98

Although older monoamine oxidase inhibitors (MAOIs) are effective in the treatment of depressive disorders, they are underutilized in clinical practice due to main concerns about interaction with tyramine-containing food, and side effects. Efforts to address these safety issues led to the development of a transdermal formulation of selegiline, called selegiline transdermal system (STS). STS has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of major depression. Transdermal administration of selegiline bypasses gastrointestinal absorption and first-pass metabolism. Therefore, STS permits inhibition of monoamine oxidase (MAO)-A and MAO-B enzymes in the brain while preserving the activity of MAO-A in the gastrointestinal system, thereby minimizing the risk of possible interactions with tyramine-rich foods. Tyramine challenge tests have confirmed that dietary modifications are not required with the 6 mg STS. The FDA has required dietary modifications with the 9 mg and 12 mg STS. Compared to oral administration, transdermal selegiline leads to sustained (minimal peak-trough fluctuations) plasma concentrations of the parent compound, increasing the amount of drug delivered to the brain. The efficacy of STS has been established in several short-term and one long-term randomized controlled trials. In clinical trials, application site reactions and insomnia were observed more frequently with STS than placebo. Rates of orthostatic hypotension, sexual dysfunction and weight gain were comparable between STS and placebo. STS is a new generation of MAOI with superior safety profile to older MAOIs. It increases the pharmacological options available to treat depressive disorders and may benefit patients with major depression with atypical features and resistant depression. It is important for health-care professionals to be informed about the properties of STS.
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PMID:Transdermal selegiline. 1761 8