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)

Pramipexole is a novel nonergoline dopamine agonist with a preference for the dopamine D3 receptor subtype. Its efficacy and safety in the treatment of advanced Parkinson's disease has been investigated in several clinical studies. This review provides a summary of the data currently available, particularly in reference to the recent results of the European clinical phase III study and the potential tremorlytic activity of pramipexole. Interim analysis of the open-label European clinical phase III study has provided evidence of long-term efficacy and safety of pramipexole. In another study pramipexole has been shown to be significantly superior to placebo with an improvement in tremor score by 48% (vs. 13% in the placebo group). In addition to its likely usefulness in the treatment of rest tremor in Parkinson's disease, data suggest that pramipexole is of interest due to its reported low frequency of cardiovascular and gastrointestinal side-effects. However, studies comparing pramipexole with other antiparkinsonian agents would be useful to further define its benefits in the treatment of tremor-dominant Parkinson's disease and to further document its favourable adverse event profile.
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PMID:Pramipexole in the treatment of advanced Parkinson's disease. 1105 55

Tremor is one of the cardinal signs of Parkinson's disease (PD) but its response to antiparkinsonian medication is variable. It has been postulated that pramipexole may have a stronger antiparkinsonian tremor effect than pergolide, another direct acting dopamine agonist medication, possibly because the former has preferential affinity for the dopamine D3 receptor. The purpose of this pilot study was to compare the effects of a single oral dose of either pramipexole (Pr) or pergolide (Pe) or placebo (Pl) on parkinsonian tremor and the motor (part III) subsection of the UPDRS. Ten patients (6 men, 4 women), mean age 65.3 years, mean duration from diagnosis of 2.6 years, with tremor dominant PD were recruited. On three separate occasions a single dose of pramipexole (salt) 500 microg, pergolide 500 microg or placebo were administered in random order to each patient, who were pretreated with domperidone and had their antiparkinsonian medication withheld from midnight before study. After each medication patients were assessed at baseline and then every 30 min for 4 hr using a 0 to 10 tremor rating scale and the UPDRS (part III) in a double-blind protocol. Adverse effects were systematically recorded. The results demonstrate that 500 microg of either pramipexole or pergolide reduced PD rest tremor scores to a similar degree, which at peak effect was significantly greater than placebo (respectively Pe v Pl: P < 0.006, Pr v Pl: P < 0.033). The two active drugs also had weaker beneficial effects on the UPDRS part III. Pergolide, however, was significantly more likely than pramipexole to cause nausea (P = 0.005) or vomiting (P = 0.014).
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PMID:Double-blind, single-dose, cross-over study of the effects of pramipexole, pergolide, and placebo on rest tremor and UPDRS part III in Parkinson's disease. 1253 11

Essential tremor (ET) is a prevalent condition manifesting with progressive action tremor. Although ET was traditionally viewed as a sporadic disease, a significant proportion of cases report a positive family history of tremor. Autosomal dominant inheritance can be demonstrated in many families. Previously, genome-wide linkage studies in families mapped three loci for ET, hereditary essential tremor-1 (ETM1), ETM2 and ETM3. However, no causal mutation has been replicated in candidate genes within these loci, including dopamine D3 receptor (DRD3) and HS1-binding protein 3 (HS1BP3). Recently, the first genome-wide association study in ET followed by replication studies conducted in diverse populations identified a significant association between the leucine-rich repeat and Ig domain containing 1 gene (LINGO1) SNP rs9652490 and risk for ET Although further novel variants were indentified in LINGO1 and its paralog LINGO2 that may be associated with risk for ET, the pathogenic mechanisms involved remain elusive. Given the possibility that ET as a complex trait may be influenced by the combined effects of rare variants, novel high-throughput technologies sequencing all exons across the genome (exome sequencing) or the whole genome (genome sequencing) may become crucial in understanding/deciphering the genetic background of ET.
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PMID:Genetics of essential tremor. 2216 13

Cariprazine is a dopamine D3-preferring D3/D2 receptor partial agonist in late-stage clinical development for the treatment of bipolar disorder (manic/mixed and depressive episodes), as well as for schizophrenia, and as an adjunctive agent for the treatment of major depressive disorder. Three phase 2 or 3, 3-week, randomized controlled trials in bipolar mania or mixed episodes have been completed and reported as poster presentations or in press releases by the manufacturer. Superiority over placebo on the Young Mania Rating Scale total score was evidenced for daily doses of cariprazine 3-12 mg/day. In short-term randomized controlled trials, cariprazine does not appear to adversely impact metabolic variables, prolactin, or the electrocardiogram (ECG) QT interval. The most commonly encountered adverse events in the mania trials were extrapyramidal disorder, akathisia, insomnia, vomiting, restlessness, sedation, vision blurred, and pain in extremity in the phase 2 trial where this was presented in a poster, and akathisia, extrapyramidal disorder, tremor, dyspepsia, vomiting, dizziness, diarrhea, somnolence, restlessness, and pyrexia for the phase 3 trial where this was presented in a poster. With the exception of akathisia and extrapyramidal disorder, the differences in incidence versus placebo for these events were generally small. If approved by regulatory authorities, cariprazine would join aripiprazole as the second dopamine receptor partial agonist antipsychotic available for clinical use in persons with bipolar mania or mixed episodes. Cariprazine differs from aripiprazole in terms of dopamine D3 receptor selectivity. Further studies would be helpful to discern the distinguishing features of cariprazine from other antimanic agents.
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PMID:Cariprazine in bipolar disorder: clinical efficacy, tolerability, and place in therapy. 2336 32

The dopamine D3 receptor (DRD3) Ser9Gly variant has attracted more attention since the variant was observed to be associated with risk of essential tremor (ET). A number of association studies concerning the DRD3 Ser9Gly variant and ET susceptibility have been conducted in various populations. However, some results were contradictory. To derive a more precise estimation of the relationship between the DRD3 Ser9Gly variant and the genetic risk of ET, we performed a comprehensive meta-analysis which included seven case-control studies. The meta-analysis was conducted in four genetic models: dominant, recessive, heterozygous, and homozygous. The odds ratio and 95% confidence intervals were used as the measure of association. The combined results of overall analysis showed a lack of association of the DRD3 Ser9Gly variant and ET, regardless of the genetic model of Ser9Gly. Publication bias and heterogeneity were absent in most analyses. In conclusion, the present meta-analysis does not support the notion that the DRD3 Ser9Gly variant is a genetic risk factor for ET.
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PMID:Meta-analysis of the influence of DRD3 Ser9Gly variant on susceptibility for essential tremor. 2405 3