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)

Effects of MKC-242 (5-[3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy]-1,3-b enzodioxole HC1), a novel 5-HT1A-receptor agonist, and reference compounds on wrap restraint stress-induced defecation were evaluated in rats. Wrapping restraint stress increased defecation in rats. The increase was attenuated by putative 5-HT1A-receptor agonists, MKC-242 and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). The suppressive effect of MKC-242 on wrap stress-induced defecation was antagonized by prior administration of a 5-HT1A-receptor antagonist, WAY100135. MKC-242 did not affect spontaneous defecation and 5-HT-induced defecation. Diazepam and amitriptyline also significantly reduced the stress-induced defecation. However, amitriptyline showed a potent anti-cholinergic effect in the oxotremorine-induced tremor test and reduced spontaneous defecation. In contrast to MKC-242 and 8-OH-DPAT, buspirone and tandospirone tended to suppress the increase at high doses. A major metabolite of buspirone and tandospirone, 1-(2-pyrimidinyl)piperazine, antagonized the suppressive effect of MKC-242. These findings suggest that stimulation of 5-HT1A receptors reduces stress-induced defecation but not spontaneous and 5-HT-induced defecation and that MKC-242 may be useful for the treatment of irritable bowel syndrome.
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PMID:Reduction of wrap restraint stress-induced defecation by MKC-242, a novel benzodioxan derivative, via 5-HT1A-receptor agonist action in rats. 971 68

Over the last few years, a number of cases of extrapyramidal disorders associated with trimetazidine (TMZ) use has been reported. Here, we report on a series of 21 cases. All but one of the patients (mean age 74) had been taking TMZ for several years. The indication for prescription of TMZ could not be identified in seven cases. The TMZ-associated adverse drug reactions were typical parkinsonism (akinesia and/or rigidity and/or rest tremor) in 17 cases, gait disorders in three cases (one with orthostatic tremor), and restless leg syndrome in one case. Discontinuation of TMZ led to complete disappearance of the symptoms in 16 cases and a significant reduction in the five other patients. TMZ has the same piperazine core as the dopamine antagonists flunarizine and cinnarizine (both of which have been reported to induce extrapyramidal symptoms). Hence, striatal D2 receptor blockade could result in the onset or the worsening of extrapyramidal disorders. Even though this adverse drug reaction is now listed in TMZ's Summary of Product Characteristics (because of the initial reports), the risk remains poorly known by clinicians. There is a need to raise awareness of this phenomenon and to reassess TMZ 's risk-benefit ration, especially in the elderly.
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PMID:Extrapyramidal adverse drug reactions associated with trimetazidine: a series of 21 cases. 2204 94

Cariprazine (RGH-188, trans-4-{2-[4-(2,3-dichlorophenyl)-piperazine-1-yl]-ethyl}-N,N-dimethylcarbamoyl-cyclohexyl-amine hydrochloride), is a novel antipsychotic with dopamine D2 and D3 receptors antagonist-partial agonist properties. Cariprazine has also moderate affinity for serotonin 5-hydroxytryptophan (5-HT) 1A receptors, high affinity for 5-HT1B receptors with pure antagonism and low affinity for 5-HT2A receptors. Randomized, double blind, placebo controlled, flexible-dose (3-12 mg/day) studies have demonstrated cariprazine is effective in both schizophrenia and acute manic episodes associated with bipolar disorder. The incidence of serious adverse events in cariprazine arm was no different than in placebo arm in these studies. The most common adverse events were extrapyramidal symptoms, headache, akathisia, constipation, nausea, and dyspepsia which can be explained with cariprazine's partial dopamine agonism. Although cariprazine treatment was associated with a higher incidence of treatment-emergent adverse events, particularly akathisia and tremor, common side effects of marketed second generation antipsychotics such as weight gain, metabolic disturbances, prolactin increase or QTc prolongation were not associated with cariprazine, probably due to its moderate to low binding affinity for histamine H1 and 5-HT2C receptors. Animal studies show that cariprazine may have additional therapeutic benefit on impaired cognitive functioning with D3 receptor activity, however clinical data is still scarce. The aim of this article is to review the potential use of cariprazine for the treatment of acute manic episodes in the light of the preclinical and clinical trials reported to date.
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PMID:Clinical potential of cariprazine in the treatment of acute mania. 2404 86


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