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)

We aimed to determine whether the cholinesterase inhibitor rivastigmine, an inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), would improve quality of life and cognitive function in 16 clinically stable subjects affected by schizophrenia in the residual phase. Study subjects began rivastigmine treatment at a dose of 1.5 mg bid. This dose was escalated at monthly intervals in increments of 1.5 mg bid to a maximum of 6 mg bid. All subjects were followed for 12 months. Quality of life was assessed using the Satisfaction with Life Domains Scale (SLDS, a self-report scale containing 10 "satisfaction" items); cognitive function, attentional function, and aspects of learning and memory were evaluated using common neuropsychological tests. Psychopathology was evaluated by means of the Brief Psychiatric Rating Scale (BPRS). Rivastigmine treatment resulted in significant improvements in quality of life, which were paralleled by significant improvements in cognitive function, learning and memory, and trends for improvement in attention. The BPRS factor "anergia" showed significant improvement, while low baseline scores in other psychotic factors did not permit further improvements. There were no reports of nausea or vomiting. In conclusion, rivastigmine significantly improved quality of life in subjects with schizophrenia. These benefits may relate to the drug's effects on cognitive deficits and negative symptoms associated with the condition.
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PMID:Effects of rivastigmine on cognitive function and quality of life in patients with schizophrenia. 1464 12

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and dosage and administration of aripiprazole are discussed. Aripiprazole is a third-generation antipsychotic agent indicated for use in the treatment of schizophrenia. Unlike other antipsychotics, aripiprazole demonstrates mixed D2 and serotonin (5-HT1A) receptor agonist-antagonist activity that is hypothesized to improve schlzophrenia's positive and negative symptoms; the drug has been referred to as a dopamine-serotonin stabilizer. Aripiprazole is well absorbed, with peak plasma concentrations occurring within three to five hours after administration. The oral availability is 87%. The mean elimination half-life is about 75 hours for aripiprazole and 94 hours for its active metabolite. In controlled, randomized, multicenter trials, aripiprazole has demonstrated efficacy in the treatment of schizophrenia comparable to that of haloperidol and superior to placebo. In a single clinical trial, aripiprazole was superior to placebo in the treatment of acute mania. The most frequent adverse effects are headache, anxiety, insomnia, nausea, vomiting, and lightheadedness. Because aripiprazole is a substrate of both cytochrome P-450 isoenzymes 3A4 and 2D6, there is a potential for other drugs to affect its metabolism. The recommended starting dosage is 10 or 15 mg daily, preferably administered with meals. Aripiprazole offers an alternative to second-generation antipsychotic agents in the treatment of schizophrenia.
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PMID:Aripiprazole. 1468 20

Risperidone is one of the second-generation antipsychotics (SGAs). Use of SGAs or so-called atypical antipsychotics is becoming more frequent because they are more efficacious and safer than typical antipsychotics. This is due to their ability to occupy some other receptors as well as dopamine type 2 (D(2)) receptors in the brain. Risperidone has more affinity for serotonin type 2 (5-HT(2)) than for D(2) receptors. This accounts for its better treatment of negative symptoms of schizophrenia and fewer extrapyramidal side effects when compared with typical antipsychotics. Common side effects associated with risperidone include extrapyramidal symptoms, dizziness, nausea, weight gain, sleep disturbance, and sexual dysfunction. We describe here a case of risperidone-induced hypothermia. Body temperature is regulated by the preoptic anterior hypothalamus with involvement of dopamine, serotonin, norepinephrine, and alpha-adrenergic receptors. Experimental data suggest that stimulation of 5-HT(2) and dopamine receptors can increase the body temperature. Additional clinical evidence indicates potent antagonists of 5-HT(2) are more likely to cause hypothermia. Risperidone has higher potency for occupying 5-HT(2) than D(2) receptors.
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PMID:A case of risperidone-induced hypothermia. 1513 39

The 5-HT3A receptor, a ligand-gated ion channel, is involved in pain pathways, nausea and emesis, and irritable bowel syndrome, and may play a role in the pathogenesis of psychiatric diseases such as schizophrenia and depression. Recently, a naturally occurring variation (ProArg) in the second intracellular loop of the human (h) 5-HT3A receptor was identified in a schizophrenic patient. Because the substitution of proline, an alpha-imino acid, by arginine may affect the conformation of the whole receptor, the aim of the present study was to determine the pharmacological and functional properties of this variant compared to the wild-type receptor in stably transfected HEK293 cells. Studies of binding of [H]GR65630, a 5-HT3 receptor antagonist, to membranes (saturation and competition experiments with 5-HT3 receptor ligands) and patch-clamp studies of agonist-induced currents in outside-out patches were carried out. In comparison to the wild-type, the variant receptor exhibited no changes in the receptor density and the affinities for nine representative ligands (five agonists and four antagonists). The potencies and efficacies of three 5-HT3 receptor agonists in inducing currents through the ion channel and the potencies of two 5-HT3 receptor antagonists in blocking 5-HT-evoked currents did not differ between wild-type and variant receptors. In addition, there were no differences in the desensitization kinetics of both receptor isoforms. In conclusion, the ArgPro variation of the h5-HT3A receptor does not change ligand binding to the h5-HT3A receptor, nor does it modify current through the receptor channel.
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PMID:Pharmacological and electrophysiological properties of the naturally occurring Pro391Arg variant of the human 5-HT3A receptor. 1516 4

This is a review of the uses of levomepromazine in psychiatry, based upon MEDLINE, PSYCLIT and EMBASE literature searches. The main indications for this drug in psychiatry are schizophrenia and schizoaffective disorder. Levomepromazine's sedative properties particularly fit it to use in psychiatric intensive care. There is also some evidence to suggest it has efficacy in drug-resistant psychosis, although this property of the drug does require further research. In other areas of medicine levomepromazine has been used in: alleviating bronchoconstriction; as a preoperative sedative; in terminal pain control and postoperative analgesia; and in the control of nausea. Some antimycobacterial properties have been recorded. The drug should not be prescribed to patients at high risk of accidental or suicidal overdose.
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PMID:Focus on levomepromazine. 1570 Dec 5

Aripiprazole is a new chemical entity with a unique pharmacological profile. It has strong affinities for certain dopamine receptors, and intermediate affinity for serotonin, adrenergic and histamine receptors. Partial agonism of the D2 dopamine and 5HT1A serotonin receptors, and antagonism of the 5HT2 serotonin receptor are believed to be the functional basis of its therapeutic efficacy. Its clinical effects are best documented in patients suffering from schizophrenia and bipolar disorder, in which it has been demonstrated to have antipsychotic and antimanic properties superior to placebo in dose ranges of 10-30 mg/day. Two published longer term trials document maintenance of antipsychotic effects and relapse prevention in schizophrenia patients. In general, aripiprazole seems to be a well-tolerated drug, especially with regard to metabolic side effects. The most commonly reported side effects include restlessness/akathisia, somnolence and nausea. These may be dose-dependent and usually occur early on during treatment, with many patients developing tolerance. Aripiprazole is an interesting and important addition to the currently available spectrum of antipsychotic drugs. Further studies in other indications and clinical trials that confirm results from the Phase II and III clinical development programme are eagerly awaited.
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PMID:Aripiprazole. 1619 61

The literature related to somatoform disorders in the workplace is very limited, and these disorders need more attention from mental health professionals in the workplace as well as from employers. Over the last decade, major changes have taken place in the work environment in Japan. More stress and less support from supervisors or colleagues in the workplace have made employees stressed out. The number of employees with mental disorders, including somatoform disorders, taking sick leave has significantly increased. In our multi-centre collaborative study, somatoform disorders were the third most prevalent psychiatric disorder in employees, after mood and schizophrenic disorders. Employees with neurotic disorders manifested physical symptoms more frequently than those without. Young employees frequently reported somatic symptoms such as general malaise, nausea, constipation, diarrhoea, headache, stiff shoulder, and dizziness. A rational new approach is needed to tackle this important psychopathology increasingly seen among employees.
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PMID:Somatoform disorders in the workplace in Japan. 1645 78

Recent investigations suggest the efficacy of olanzapine in cancer patients with intractable vomiting or chemotherapy-induced nausea. Olanzapine,indicated for schizophrenia in Japan, has an affinity for multiple neurotransmitter receptors including dopaminergic, serotonergic, histaminergic, adrenergic and muscarinic receptors. This pharmacological activity thus has a potential role in the treatment of nausea and vomiting. In the present study, olanzapine was given to five cancer patients with refractory vomiting to standard medications. In 3 cases, olanzapine resolved vomiting completely and also improved anorexia, In 2 cases, vomiting was controlled for a limited period. No adverse effect was observed. These results suggest olanzapine is a useful agent for the management of both vomiting and anorexia.
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PMID:[Olanzapine use in cancer patients for refractory vomiting]. 1653 16

In a European, multicenter, double-blind study, 244 adolescents, 13 to 18 years old, with major depression were randomized to treatment with citalopram (n = 124) or placebo (n = 120). One third of the patients in both groups withdrew from the study. No significant differences in improvement of scores from baseline to week 12 between citalopram and placebo were found. The response rate was 59% to 61% in both groups according to the Schedule for Affective Disorders and Schizophrenia for school-aged children-Present episode version (Kiddie-SADS-P) (depression and anhedonia scores < or =2) and Montgomery Asberg Depression Rating Scale (MADRS) (> or =50% reduction). Remission (MADRS score < or =12) was achieved by 51% of patients with citalopram and 53% with placebo. A post hoc analysis revealed that more than two thirds of all patients received psychotherapy during this study. For those patients not receiving psychotherapy, there was a higher percentage of Kiddie-SADS-P responders with citalopram (41%) versus placebo (25%) and a significantly higher percentage of MADRS responders and remitters with citalopram (52% and 45%, respectively) versus placebo (22% and 19%, respectively). Mild to moderate treatment-emergent adverse events were reported in 75% citalopram and 71% of placebo patients, most commonly headache, nausea, and insomnia. Serious adverse events occurred in 14% to 15% in both groups. Suicide attempts, including suicidal thoughts and tendencies, were reported by 5 patients in the placebo group and by 14 patients in the citalopram group (not significant) with no pattern with respect to duration of treatment, time of onset, or dosage. In contrast, the suicidal ideation (Kiddie-SADS-P) single item showed worsening more frequently in the placebo (18%) than in the citalopram group (8%).
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PMID:A randomized, double-blind, placebo-controlled study of citalopram in adolescents with major depressive disorder. 1750 98

Ampakines act as positive allosteric modulators of AMPA-type glutamate receptors and facilitate hippocampal long-term potentiation (LTP), a mechanism associated with memory storage and consolidation. The present study investigated the acute effects of farampator, 1-(benzofurazan-5-ylcarbonyl) piperidine, on memory and information processes in healthy elderly volunteers. A double-blind, placebo-controlled, randomized, cross-over study was performed in 16 healthy, elderly volunteers (eight male, eight female; mean age 66.1, SD 4.5 years). All subjects received farampator (500 mg) and placebo. Testing took place 1 h after drug intake, which was around Tmax for farampator. Subjects performed tasks assessing episodic memory (wordlist learning and picture memory), working and short-term memory (N-back, symbol recall) and motor learning (maze task, pursuit rotor). Information processing was assessed with a tangled lines task, the symbol digit substitution test (SDST) and the continuous trail making test (CTMT). Farampator (500 mg) unequivocally improved short-term memory but appeared to impair episodic memory. Furthermore, it tended to decrease the number of switching errors in the CTMT. Drug-induced side effects (SEs) included headache, somnolence and nausea. Subjects with SEs had significantly higher plasma levels of farampator than subjects without SEs. Additional analyses revealed that in the farampator condition the group without SEs showed a significantly superior memory performance relative to the group with SEs. The positive results on short-term memory and the favorable trends in the trail making test (CTMT) are interesting in view of the development of ampakines in the treatment of Alzheimer's disease and schizophrenia.
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PMID:Acute effects of the ampakine farampator on memory and information processing in healthy elderly volunteers. 1711 38


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