Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Non-motor symptoms in Parkinson's disease (PD), such as excessive daytime sleepiness, 'sleep attacks', insomnia, restless legs syndrome and rapid eye movement sleep behavior disorder, are common and provide a challenge to treatment. These sleep symptoms are also described in patients suffering from the sleep/wake disorder, narcolepsy. The International Classification of Sleep Disorders (ICSD-2) narcolepsy criteria uses a number of markers for diagnosis, of which lack or deficiency of cerebrospinal fluid (CSF) hypocretin-1 levels is a key marker. Hypocretin neurons prominently located in the lateral hypothalamus and perifornical nucleus have been proposed to interact with mechanisms involving sleep and arousal. Low hypocretin-1 levels in the CSF have been shown to correlate with hypothalamic hypocretin cell loss in narcolepsy and other forms of hypersomnia; therefore, it has been proposed that degenerative damage to hypocretin neurons (such as in PD) may be detected by low CSF hypocretin-1 concentrations, and may also explain the sleep symptoms experienced by some PD patients. To date, there is mixed conflicting data describing hypocretin-1 levels in the CSF of patients with parkinsonism associated with sleep symptoms, with most studies showing no significant decrease when compared with controls. However, hypocretin-1 CSF deficiency has been shown in some studies to be more prominent in PD patients with sleep symptoms versus those without. Notably, the hypocretin system has been shown not to be selectively disrupted, with one study showing melanin concentrating hormone cell loss in the same patients with hypocretin loss. It is likely that hypocretin deficiency in PD patients occurs secondary to collateral damage caused by the neurodegenerative process involving the hypothalamus. Awareness of narcoleptic events in PD is important for driving related advice, in addition to the possible use of dopamine D3 receptor active agonists.
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PMID:Narcolepsy in Parkinson's disease. 2051 4

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

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