Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is a new, potentially fatal disorder that is infrequently reported. The apparent rareness may be because of a lack of recognition of the syndrome or its predisposing factors. Fluoxetine (Prozac, Dista Products Co, Division of Eli Lilly Co, Indianapolis, IN), sertraline (Zoloft, Roerig Division, Pfizer Inc, New York, NY), and paroxetine (Paxil, SmithKline Beecham Pharmaceuticals, Philadelphia, PA) belong to a new class of antidepressant medication: the serotonin reuptake-inhibitors (SRIs). The relative safety profile of the SRIs has led to their widespread use. However, a syndrome of excessive serotonergic activity, the "serotonin syndrome" (SS), has recently been recognized. It is characterized by changes in mental status, hypertension, restlessness, myoclonus, hyperreflexia, diaphoresis, shivering, and tremor. A high index of suspicion is required to make the diagnosis in these acutely ill patients. The most common agents implicated in SS are the monoamine oxidase inhibitors in combination with L-tryptophan or fluoxetine. A case of a patient with significant peripheral vascular disease who developed SS while taking paroxetine and an over-the-counter cold medicine is reported. There have been no prior reports of this interaction. Discontinuation of the offending agents, sedation, and supportive care are the mainstays of treatment. The interactions of serotonin with platelets and vascular endothelium are also discussed.
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PMID:The serotonin syndrome associated with paroxetine, an over-the-counter cold remedy, and vascular disease. 766 67

Tremor, akinesia, rigidity and postual instability are key signs of Parkinson's disease. The most important one is akinesia, which includes decreased spontaneous locomotor activity, slowness of movement, awkwardness and freezing. On the other hand, an electrical focal lesion in the brain, neurotoxin to dopaminergic neurons such as 6-hydroxydopamine (6-OHDA) or I-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), cholinomimetic tremorogenic agents such as oxotremorine or tremorine, monoamine depleting agents such as reserpine or tetrabenazine, or dopamine receptor antagonists such as haloperidol are applied to render animal parkinsonism. The estimation of locomotor activity can be done accurately in animal models. Tremor can be studied using the animals treated by cerebral focal lesion, neurotoxins or cholinomimetics. Skillfulness is hard to estimate in animals, however, it can be done in primates. Freezing appeared in patients with levodopa treatment over a long period. This is a specific motor sign in Parkinson's disease, and cannot be observed in animals. Supplementing dopamine by levodopa administration, retarding the metabolism of levodopa or dopamine by dopa decarboxylase inhibitor (DCI), monoamine oxidase inhibitor type B (MAO-B) inhibitor or catechol-O-methyltransferase (COMT) inhibitor, dopamine receptor agonists, anticholinergic agents, dopamine release enhancer/ uptake inhibitor, N-methyl-D-aspartate (NMDA) receptor antagonists, adenosine receptor antagonists, neurotrophic factors, GM1-ganglioside and nicotinic receptor agonists have been applied in the treatment of Parkinson's disease or are under investigation for patients. Agents to facilitate nerve growth or to inhibit the degeneration of nerves will be developed in the future.
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PMID:[Recent progress in development of psychotropic drugs (3)--Antiparkinsonian agents applied in the treatment of Parkinson's disease or are under investigation for patients or model animals]. 890

The serotonin syndrome is frequently characterized by minor neurologic manifestations that regress rapidly (such as confusion, tremor, ...). Many medications including tricyclic antidepressants, serotonin reuptake inhibitors, tryptophan and the association of monoamine oxidase inhibitors together with a serotoninergic agent have been implicated in this syndrome. In certain cases, and for poorly understood reasons, clinical manifestations can include circulatory collapse, malignant hyperthermia, convulsions and rhabdomyolysis. These forms are often fatal. Treatment, other than the withdrawal of the offending drug, is symptomatic. Dialysis may be of value in withdrawing the drug from the circulatory system. We report a patient with the serotonin syndrome of favorable outcome due to an overdose of moclobemide and clomipramine.
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PMID:Serotonin syndrome due to an overdose of moclobemide and clomipramine. A potentially life-threatening association. 903 53

The safety and efficacy of brofaromine, a reversible and selective monoamine oxidase inhibitor, were examined in a multicenter trial of 102 outpatients with social phobia. After a 1-week placebo washout, subjects were randomly assigned to 10 weeks of treatment with either brofaromine (N = 52) or placebo (N = 50). Brofaromine dosage began at 50 mg/day and was titrated to a maximum of 150 mg/day, depending on treatment response. Brofaromine produced a significantly greater change from baseline in Liebowitz Social Anxiety Scale (LSAS) scores compared with placebo, F(1) = 6.01, p < 0.016. Mean LSAS scores decreased from 81.8 at baseline to 62.6 at endpoint for brofaromine, t = 5.41,p < 0.001, and from 79.8 to 70.7 for placebo, t = 3.66, p < 0.001. Eleven of the 14 brofaromine early terminators discontinued because of adverse experiences, as did 4 of the 17 placebo early terminators. Side effects more common with brofaromine than placebo included insomnia, dizziness, dry mouth, anorexia, tinnitus, and tremor. No clinically significant variations in vital signs or laboratory values were found. The findings are consistent with the clinical efficacy for the treatment of social phobia.
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PMID:Brofaromine for social phobia: a multicenter, placebo-controlled, double-blind study. 924 Oct 3

Once a diagnosis of idiopathic parkinsonism has been made, the choice and timing of therapy depend almost entirely on the patient's need for symptomatic relief, as no presently available therapy has any effect on the pathogenesis of the disease. Five categories of drugs are available for the treatment of idiopathic parkinsonism. Anticholinergic agents are effective against tremor but have prominent adverse effects. Amantadine has similar effects but is more active against rigidity and bradykinesia. Selegiline is a monoamine oxidase-B inhibitor; once thought to affect the pathogenesis of idiopathic parkinsonism, it is now known to offer only symptomatic relief. The dopamine agonists (bromocriptine, pergolide, and lisuride) stimulate D2 receptors; they have antiparkinsonian effects and tolerance profiles broadly similar to those of levodopa but are slightly less efficacious. Pleural effusions and pulmonary fibrosis are unusual but important complications of these drugs; chest x-ray examinations are therefore recommended for all patients starting such treatment. Levodopa (combined with an extracerebral decarboxylase inhibitor to prevent nausea, the main adverse effect) has become the standard antiparkinsonism treatment. Patients using this preparation can suffer considerable variations in mobility and dyskinesia, which may be related to rapid, large-scale oscillations in plasma levodopa concentrations. Controlled-release (CR) preparations have been developed in an attempt to minimize these fluctuations and reduce long-term side effects. There is no universally agreed treatment for idiopathic parkinsonism. However, experience shows that a good balance of antiparkinsonian activity and adverse effects can be obtained by initiating treatment with a combination of levodopa and a decarboxylase inhibitor. A dopamine agonist can be added if the disease progresses and increased therapeutic activity is required.
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PMID:Early idiopathic parkinsonism: initiation and optimization of treatment. 935 91

T-794 is a new reversible inhibitor of MAO type A. In order to predict its clinical utility as an antidepressant, we examined its pharmacological profile (i.e., MAO inhibitory activity, antidepressant-like activity and safety) in vivo in rodents. The p.o. administration of T-794 potentiated L-5-hydroxytryptophan-induced symptoms with ED50 = 1.01 mg/kg (mice) or 1.15 mg/kg (rats), and L-dopa-induced behavior with ED50 = 5.90 mg/kg (mice), whereas it did not alter the effect of beta-phenylethylamine even at 100 mg/kg (mice). In the L-5-hydroxytryptophan test in rats, the activity of T-794 (at twice the dose of ED50) disappeared by 8 h; the duration of action was similar to that of moclobemide. These results confirm the previous biochemical results that MAO-A inhibition by T-794 is highly selective and of short duration. T-794 was effective in three animal models of depression: reserpine reversal (mice, rats), behavioral despair test (mice) and learned helplessness (rats). In these tests, it had potency similar to or greater than moclobemide, tranylcypromine or imipramine. The p.o. administration of T-794 (30 mg/kg) did not affect the pressor effect of tyramine in anesthetized rats, whereas moclobemide (30 mg/kg) and tranylcypromine (6 mg/kg) potentiated the effect. Acute toxicity of T-794 proved to be very low (maximal tolerated dose > 2 g/kg p.o.) in contrast to brofaromine (maximal tolerated dose = 150 mg/kg p.o.). Unlike tricyclic antidepressants, T-794 did not prevent the oxotremorine-induced tremor even at 100 mg/kg p.o.; in this it demonstrated a lack of the anticholinergic activity. These results suggest that T-794 is an effective and particularly safe antidepressant and that it may make an important contribution in the treatment of depressive disorders.
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PMID:In vivo characterization of T-794, a novel reversible inhibitor of monoamine oxidase-A, as an antidepressant with a wide safety margin. 949 58

Parkinson's disease is a progressive degenerative disorder of the central nervous system. The hallmark physical signs are tremor, rigidity and bradykinesia. Idiopathic Parkinson's disease is caused by the progressive loss of dopaminergic neurons in the substantia nigra and nigrostriatal pathway of the midbrain. Secondary parkinsonism may be caused by certain drugs (e.g., metoclopramide and haloperidol) or by cerebrovascular disease (e.g., multiple lacunar strokes). The disease can usually be diagnosed based on the history and physical findings. Dopamine replacement is still considered the most efficacious treatment for Parkinson's disease, but dopamine agonists, formerly prescribed only as adjunctive therapy, are emerging as useful initial therapy. Other pharmacologic treatments include drugs that inhibit dopamine-metabolizing enzymes (monoamine oxidase-B and catechol O-methyltransferase). Injections of botulinum toxin can be helpful in patients with associated dystonia or blepharospasm. Surgery may be indicated for certain patients or when symptoms do not respond to medical therapy. Additional adjunctive therapies include physical therapy, nutritional counseling and techniques to help patients manage emotional and cognitive changes related to the disease.
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PMID:Update on Parkinson's disease. 1022 2

Four major components of the mechanism of action have been identified for the antiparkinsonian drug budipine up to now. 1) The primary action of budipine is an indirect dopaminergic effect as shown by facilitation of dopamine (DA) release, inhibition of monoamine oxidase type B (MAO-B) and of DA (re) up-take and stimulation of aromatic L-amino acid decarboxylase (AADC), which in sum might be responsible for enhancing the endogenous dopaminergic activity. 2) Radioligand and functional studies at the N-methyl-D-aspartate (NMDA) type glutamate receptor characterize budipine as a low-affinity, uncompetitive antagonist with fast kinetics and moderate voltage-dependency at the phencyclidine (PCP) binding site, comparable to that observed with amantadine, thereby counteracting an increased excitatory glutamatergic activity. 3) The antimuscarinic action of budipine, verified by functional and binding studies at native muscarinic M1-M3 and human recombinant m1-m5 receptor subtypes in vitro, is up to 125-fold weaker than that of biperiden and corresponds to its approximately 100-fold lower potency to cause experimentally-induced peripheral antimuscarinic effects and explains only part of its high potency, which equals biperiden, to suppress cholinergically evoked tremor. 4) An additional inhibition of striatal gamma-aminobutyric acid (GABA) release by budipine may be beneficial to suppress an increased striatal GABAergic output activity. The contribution of other observed effects to the therapeutic action of budipine, i.e. weak stimulation of noradrenaline and serotonin release, binding to brain sigma1 receptors and blockade of histamine H1 receptors, is not yet clear. By means of these multiple mechanisms, budipine might correct the imbalance of striatal output pathways by restoring DA levels in the striatum, and positively influence the secondary changes in other transmitter systems (glutamate, acetylcholine, GABA) observed in Parkinson's disease.
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PMID:Multiple mechanisms of action: the pharmacological profile of budipine. 1037 Sep 4

The serotonin(5-HT) syndrome(SS) is a condition of both the central and peripheral 5-HTergic hyperstimulation, characterized by a constellation of 5-HT-related side effects(confusion, agitation, restlessness, myoclonus, hyperreflexia, diaphoresis, shivering or tremor in the setting of the recent addition of 5-HTergic agents. The SS is produced most often by the concurrent use of monoamine oxidase inhibitors and other 5-HTergic agents. However, more recent reports suggest that the tricyclic antidepressant or selective serotonin reuptake inhibitor(SSRI) monotherapy induces the SS. Recently, for the operationalized assessment of both the presence and the severity of the core symptoms of the SS, Hegerl et al. developed the Serotonin Syndrome Scale(SSS) as a modification of the diagnostic criteria of the SS proposed by Sternbach. Since, in Japan, some novel 5-HTergic agents have been, and will be in use, recognition of the SS is quite important. Therefore, for clinical application of SSS, we prepared the Japanese-language version (JSSS).
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PMID:[The Japanese version of the serotonin syndrome scale (JSSS)]. 1087 22

Motor fluctuations represent important late complications of Parkinson's disease treated with levodopa. Although treatment of these problems has improved with the emergence of numerous pharmacologic and surgical therapies, the various options can make it confusing. Pharmacologic treatment is the first step. Polytherapy is often the rule in this case with a variety of agents available as adjunctive therapy with levodopa. These adjuncts include dopamine agonists (bromocriptine, pergolide, pramipexole, ropinirole), catechol-O-methyltransferase (COMT) inhibitors (tolcapone), controlled-release formulations of levodopa, monoamine oxidase (MAO) B inhibitors (selegiline), and amantadine. The treatment can consist of any of a number of combinations of these agents. No single algorithm can be used in all patients; therapy should be individualized. Physicians treating these patients need to be well versed in late complication patterns as well as the medications chosen. In addition, optimal doses vary, and often patients are considered treatment failures and taken off medications before reaching that level. In the more complicated cases, patients should be evaluated by specialists in movement disorders. With this in mind, some guidelines are offered for the pharmacologic approach to patients with fluctuating responses to medications. For simple wearing off, controlled-release levodopa (Sinemet CR, Dupont Pharmaceuticals, Wilmington, DE), COMT inhibitors, MAO inhibitors, and dopamine agonists are reasonable options. For more complicated fluctuations, dopamine agonists with limits on levodopa are the first choice, especially when dyskinesia is present; when dyskinesia is not a factor, COMT inhibitors may be used. For dyskinesia specifically, dopamine agonists or addition of amantadine can be helpful. Surgery should be a treatment of last resort for patients in whom medical therapy fails. Patients who are candidates for medial pallidotomy should be fluctuators with severe dyskinesia and "off" periods that have not improved with pharmacologic therapy. Thalamic deep brain stimulation (DBS) should be used only in patients with tremor-predominant disease and severe intractable tremor that is unresponsive to medication and occurs not only at rest but with posture and action as well. Surgical therapy should be performed only in centers with surgeons experienced in stereotactic techniques and movement disorder specialists to ensure that the appropriate patients come to surgery and that complications are kept to a minimum. Dietary adjustment has a limited role in treating advanced Parkinson's disease.
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PMID:Parkinson's Disease: Motor Fluctuations. 1109 92


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