Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prolactin, cortisol and growth hormone (GH) responses to intravenous administration of 25 mg clomipramine (CMI) were studied in young male psychotic patients who had never received neuroleptics and suffered from schizophrenia (13 patients), delusional disorder (three patients) or schizoaffective disorder (one patient). The test was repeated after 1 month in 16 patients who were hospitalized and treated with haloperidol in doses appropriate for best clinical response (range: 7.5-40 mg daily). Symptomatology was assessed by the Brief Psychiatric Rating Scale (BPRS). There was no association of the side effects caused by the administration of CMI (nausea and emesis) to the GH responses. The side effects appeared significantly less in the after treatment trials. Treatment with haloperidol did not influence the response patterns of the three hormones. An indication that high haloperidol doses may inhibit the prolactin response to CMI was obtained when the data were compared between low (7.5-10 mg/day, mean 9.7) and high (15-40 mg/day, mean 22.0) dose subgroups. Significant positive correlations were found between the prolactin and cortisol responses to CMI in the drug-free state, and the scores in the positive symptoms subscale of the BPRS. The degree of improvement did not correlate to any of the hormonal data.
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PMID:Neuroendocrine responsivity to clomipramine challenge test in neuroleptic naive psychotic patients before and after treatment with haloperidol. 1969 52

Phosphodiesterase 4 (PDE4), the primary cAMP-hydrolyzing enzyme in cells, is a promising drug target for a wide range of conditions. Here we present seven co-crystal structures of PDE4 and bound inhibitors that show the regulatory domain closed across the active site, thereby revealing the structural basis of PDE4 regulation. This structural insight, together with supporting mutagenesis and kinetic studies, allowed us to design small-molecule allosteric modulators of PDE4D that do not completely inhibit enzymatic activity (I(max) approximately 80-90%). These allosteric modulators have reduced potential to cause emesis, a dose-limiting side effect of existing active site-directed PDE4 inhibitors, while maintaining biological activity in cellular and in vivo models. Our results may facilitate the design of CNS therapeutics modulating cAMP signaling for the treatment of Alzheimer's disease, Huntington's disease, schizophrenia and depression, where brain distribution is desired for therapeutic benefit.
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PMID:Design of phosphodiesterase 4D (PDE4D) allosteric modulators for enhancing cognition with improved safety. 2003 81

This 13-week, double-blind study evaluated the efficacy and safety of the atypical antipsychotic paliperidone palmitate (recently approved in the United States) versus placebo administered as monthly gluteal injections (after two initial doses given 1 week apart) in acutely symptomatic patients with schizophrenia. Patients (N=388) were randomly assigned (1 : 1 : 1 : 1) to paliperidone palmitate 50, 100, or 150 mg eq. or placebo. As the 150 mg eq. dose was administered to fewer patients (n=30) than planned, meaningful and definitive conclusions cannot be drawn from the results of this group. The change from baseline in Positive and Negative Syndrome Scale total score at endpoint showed improvement in both paliperidone palmitate 50 and 100 mg eq. groups but was significant only in the 100 mg eq. group (P=0.019). The paliperidone palmitate 50 (P=0.004) and 100 mg eq. (P<0.001) groups showed significant improvement in the Personal and Social Performance score from baseline to endpoint versus placebo. Common adverse events (in >or=2% of patients in any group) more frequent with paliperidone palmitate 50 or 100 mg eq. than placebo (>or=5% difference) were headache, vomiting, extremity pain, and injection site pain. Treatment with paliperidone palmitate (100 mg eq.) was efficacious and all doses tested were tolerable.
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PMID:Efficacy and safety of paliperidone palmitate in adult patients with acutely symptomatic schizophrenia: a randomized, double-blind, placebo-controlled, dose-response study. 2038 55

Nausea and vomiting are often encountered in palliative care patients. Multiple medications are available to provide relief. However, several drug combinations are usually used to treat emesis. Current research has identified several receptors that trigger nausea and vomiting, hence the difficulty of using only 1 medication to provide relief. Olanzapine is a drug approved for treatment of schizophrenia and mania. It blocks multiple neurotransmitters dopaminergic, serotonergic, adrenergic (alpha(1)), histaminergic, and muscarinic receptors. Most of these receptors are also involved in causing emesis. Studies have shown that olanzapine could be used to treat nausea and vomiting with promising results.
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PMID:Olanzapine for nausea and vomiting. 2050 43

Balancing tolerability and efficacy of medications can be problematic for clinicians when assessing appropriate therapy for patients. For antipsychotic therapy, this can be especially challenging because of the hazardous movement and metabolic effects associated with them. Paliperidone is an atypical antipsychotic used for the treatment of schizophrenia and schizoaffective disorder. A systematic review of the literature for the tolerability of the drug, paliperidone, was performed. A total of 15 articles met the criteria for inclusion representing a total of 3779 patients. Data combination was conducted using the Mantel-Haenszel method, random effects model at 95% confidence. Adverse events with the greatest incidence in the paliperidone population were any treatment emergent adverse event (68%), extra-pyramidal symptoms (23%), headache (14%), insomnia (11%), somnolence (9%), tachycardia (9%) and weight gain (8%). Reported events most likely related to paliperidone [largest attributable risks (AR)] were extra-pyramidal symptoms (AR=10), reduction in acute psychosis (AR=8), any treatment emergent adverse event (AR=6), tachycardia (AR=4), and weight gain (AR=4). Events where incidence was entirely because of paliperidone (incidence equals AR) were hypersalivation (3), dysarthria (2), and sexual dysfunction (1). Reported events totally unrelated to paliperidone (AR=0) included anxiety, asthenia, constipation, depression, dyspepsia, glucose related events, and vomiting. Overall, a 50% reduction in treatment emergent psychosis was seen in schizophrenic patients treated with paliperidone, however the reduction of a psychotic event is about equal to the occurrence of an adverse event with paliperidone.
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PMID:Tolerability of paliperidone: a meta-analysis of randomized, controlled trials. 2070 26

Serotonin (5-hydroxytryptamine) is an ubiquitary monoamine acting as one of the neurotransmitters at synapses of nerve cells. Serotonin acts through several receptor types and subtypes. The profusion of 5-HT receptors should eventually allow a better understanding of the different and complex processes in which serotonin is involved. Its role is expected in the etiology of several diseases, including depression, schizophrenia, anxiety and panic disorders, migraine, hypertension, pulmonary hypertension, eating disorders, vomiting and irritable bowel syndromes. In the past 20 years, seven distinct families of 5-HT receptors have been identified and various subpopulations have been described for several of them. Increasing number of 5-HT receptors has made it difficult to unravel the role of 5-HT receptor subpopulations due to the lack of suitable selective agents. The present review describes the different populations and nomenclature of recently discovered 5-HT receptors and their pharmacological relevance.
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PMID:Serotonin receptors - from molecular biology to clinical applications. 2094 68

Aripiprazole is a new anti psychotic with a unique receptor binding profile that combines partial agonistic activity at D2 receptor and 5-HT 1A receptor and potent antagonism at 5-HT 2A receptor. This receptor profile makes it possible for it to act as a dopamine system stabilizer. Based on various short term and long term studies, aripiprazole has been found to be effective in schizophrenia and has no significant adverse effect on QTc prolongation, prolactin, serum lipids, and has a low potential for weight gain. Present study aims to evaluate the efficacy and tolerability of aripiprazole (10-15mg/day) in the treatment of Indian patients of schizophrenia and to see its effect on QTc interval, prolactin levels, serum lipids, plasma sugar and weight gain in these patients. Outpatients with an ongoing/newly diagnosed ICD-10 Schizophrenia (n=136) were randomly assigned to 10 or 15 mg dose of Aripiprazole for a period of six weeks. Clinical response was evaluated by the Positive And Negative Symptoms Scale (PANSS), Clinical Global Impression (CGI) scale and safety was evaluated by observing spontaneously reported adverse events and changes in various laboratory parameters. Switching schizophrenic patients to aripiprazole (10/15 mg) from both conventional and atypical anti-psychotics was safe and well tolerated. Six weeks after switching to aripiprazole, patients showed improvements in PANSS scores (P< 0.001), EPS, prolactin levels and weight over the baseline levels. No difference was seen in the 10 or 15mg dose groups. One hospitalization was reported (due to hepatitis E). Common side effects reported were insomnia, somnolence, nausea, vomiting and diarrhea. Aripiprazole is a safe and effective anti psychotic in Indian patients - both in newly diagnosed, as well as, in patients not responding to or intolerant to other available typical and atypical antipsychotics.
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PMID:Open labeled, randomized, switch-over study of two fixed doses (10/15mg) of aripiprazole : to evaluate its safety and efficacy in the treatment of Indian patients of schizophrenia. 2120 77

Haloperidol is a butyrophenone neuroleptic agent characterized as a high-affinity dopamine antagonist, originally used for the treatment of schizophrenia. Awareness of the role dopamine plays in many symptoms in palliative care, such as nausea, vomiting, and delirium, has led to the use of dopamine antagonists such as haloperidol for the treatment of these symptoms in the palliative care setting. Listed as 1 of the 25 important drugs in palliative care, haloperidol can be administered by multiple routes and can be given without dose alteration in the setting of both renal and hepatic insufficiency. Haloperidol is extensively metabolized in the liver, with CYP3A4 the chief cytochrome oxidase responsible for metabolism. This article will review the pharmacology, pharmacokinetics, and current uses of haloperidol in palliative medicine. There will be an examination of the evidence base for the use of haloperidol in palliative medicine.
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PMID:Role of haloperidol in palliative medicine: an update. 2199 45

Lurasidone is a new atypical antipsychotic in the benzoisothiazoles class of chemicals. Like most second-generation antipsychotics it is a full antagonist at dopamine D(2) and serotonin 5-HT(2A) receptors, and is a partial agonist at 5-HT(1A) receptors, a property shared by some but not all older agents. It has much greater affinity for 5-HT(7) subtype receptors than other atypical antipsychotics. Pharmacokinetic studies showed that lurasidone is reasonably rapidly absorbed, with bioavailability appearing to be increased by food. Lurasidone undergoes extensive metabolism to a number of metabolites, some of which retain pharmacological activities. Metabolism is mainly by CYP3A4, resulting in steady-state concentrations that vary between individuals and are potentially affected by strong inducers and inhibitors of this enzyme. Short-term clinical trials have demonstrated the efficacy of lurasidone in acute schizophrenia, with doses of 40 and 80 mg/day giving significant improvements from baseline in the PANSS and BPRS scores. The most common adverse events are nausea, vomiting, akathisia, dizziness, and sedation, with minimal increases in the risk of developing metabolic syndrome. Lurasidone did not raise the risk of QTc interval prolongation, although additional studies are required. Long-term trials are also needed to assess the risk of new-onset diabetes. Ongoing trials in patients with bipolar disorder are being completed but, again, efficacy and safety have been investigated only in a few short-term clinical trials.
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PMID:Critical appraisal of lurasidone in the management of schizophrenia. 2257 May 47

Ischaemic colitis is a rare side effect of antipsychotics, especially phenothiazines and atypical antipsychotics. The colitis may be precipitated secondary to the anticholinergic effects of such medication rather than a direct cytotoxic effect of the drugs themselves. A 32-year-old man with a history of schizophrenia was admitted to the hospital with a history of diffuse abdominal pain and vomiting. His bloods showed leucocytosis. Sigmoidoscopy demonstrated rectal sparing acute colitis, confirmed on biopsy findings. A CT scan also showed similar findings. After careful drug review, it was decided that clozapine was the cause of colitis and promptly stopped. The patient was managed conservatively on intravenous fluids and antibiotics and made a full recovery. Any patient starting antipsychotics should be counselled on their anticholinergic side effects. Drugs should always be considered as a cause of ischaemic colitis; although an uncommon complication of antipsychotics, it can have a potentially fatal outcome.
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PMID:Clozapine-induced ischaemic colitis. 2334 90


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