Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Cariprazine is a dopamine D3-preferring D3/D2 receptor partial agonist in late-stage clinical development for the treatment of schizophrenia, as well as for bipolar disorder (manic/mixed and depressive episodes), and as an adjunctive agent for the treatment of major depressive disorder. Four phase 2 or 3, 6-week, randomized controlled trials in acute schizophrenia have been completed and reported as poster presentations or in press releases by the manufacturer. Superiority over placebo on the Positive and Negative Syndrome Scale total score was evidenced for cariprazine in daily doses of 1.5, 3.0, 4.5, 6.0, 1.5-4.5, 3.0-6.0, and 6.0-9.0 mg. A randomized controlled trial for the prevention of relapse of schizophrenia is ongoing. In short-term, randomized controlled trials, cariprazine does not appear to adversely impact metabolic variables, prolactin, or the electrocardiogram (ECG) QT interval. In the fixed-dose study of cariprazine that tested 1.5, 3.0, and 4.5 mg/day, the most commonly encountered adverse events were insomnia, extrapyramidal disorder, sedation, akathisia, nausea, dizziness, vomiting, anxiety, and constipation. However, 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. 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 second-generation antipsychotics.
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PMID:Cariprazine in schizophrenia: clinical efficacy, tolerability, and place in therapy. 2336 33

Aripiprazole, brexpiprazole and cariprazine differ from all other second-generation antipsychotics due to partial agonism at the dopamine D2 and D3 receptors. In contrast to aripiprazole, brexpiprazole has lower intrinsic dopamine D2 activity and higher affinity for the serotonin 5-HT1A and 5-HT2A receptors, while cariprazine has the highest affinity for the dopamine D3 receptor, and the longest half-life. The main adverse effect of dopamine receptor partial agonists (DRPAs) is akathisia of low-to-moderate severity, which occurs in a small proportion of patients, usually in the first few weeks of treatment. While definitive conclusions concerning differences between the DRPAs require head-to-head comparison studies, on the available evidence, akathisia is probably least likely to occur with brexpiprazole and most likely with cariprazine; the risk of akathisia with aripiprazole lies in between. Weight-gain risk is low with aripiprazole and cariprazine, but moderate with brexpiprazole. Risk of sedation is low with DRPAs, as is risk of insomnia and nausea. Partial dopamine agonism leads to a low risk for hyperprolactinaemia (and probably a low risk of sexual dysfunction). Prolactin concentrations fall in some patients (particularly those with elevated levels prior to initiating the drugs). Rates of discontinuation due to adverse effects in pivotal studies were low, and on the whole, DRPAs are well tolerated. Aripiprazole has been implicated in pathological gambling and other impulse control behaviours, likely due to partial dopamine agonist activity (there have been no reports with brexpiprazole and cariprazine). The risks for diabetes and tardive dyskinesia with DRPAs are unknown, but are likely to be low. On the basis of tolerability, DRPAs should be considered as first-line treatment options, particularly in patients with early schizophrenia.
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PMID:Comparative Tolerability of Dopamine D2/3 Receptor Partial Agonists for Schizophrenia. 3224 99