Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012833 (dizziness)
 9,689 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Clinical evidence and recent genetic findings seem to indicate an involvement of dopamine in the pathophysiology of the migraine attack. Prodromal symptomatology (mood changes, yawning, drowsiness, food craving), accompanying symptoms (nausea, vomiting, hypotension) and postdromal symptoms (mood changes, drowsiness, tiredness) may be related to dopaminergic activation. The dopaminergic system could also play a role in the headache phase, either by taking part in nociception mechanisms, or by regulating cerebral blood flow. A body of pharmacological findings seems to support this involvement. Migraine patients, between attacks, show a higher responsiveness to acute administration of dopaminergic agents. Apomorphine administration induces in migraineurs more yawns as well other dopaminergic symptoms e.g. nausea, vomiting, dizziness. Migraine has been associated with hypotension and, occasionally, with syncope. Bromocriptine causes severe orthostatic syndrome in migraine patients. Both piribedil and apomorphine markedly increase cerebral blood flow of migraine patients, thus indicating enhanced responsiveness of dopamine receptors which are involved in cerebral blood flow regulation. Interictal dopaminergic hypersensitivity has also been demonstrated by means of neuroendocrine tests. Altered dopaminergic control of prolactin secretion exists in migrainous women. L-deprenyl, a MAO-B inhibitor, is significantly more effective in reducing prolactin levels in migraineurs than in controls. Taken together, these findings support the view that hypersensitivity of peripheral and central dopaminergic receptors is a specific migraine trait. Finally, a high density of lymphocytic D5 receptors has been found in migraine sufferers, thus suggesting their upregulation. Therefore, the hypothesis that dopaminergic activation is a primary pathophysiological component in certain subtypes of migraine, namely those characterised by marked dopaminergic symptomatology, has been advanced. From this perspective, a blockade of dopaminergic hyperresponsive receptors can be considered as a rationale for the therapy of migraine.
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PMID:Dopamine involvement in the migraine attack. 1120 Jul 88

(-)-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