Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It seems that the efficacy of aripiprazole for treating schizophrenia is mediated through a combination of partial agonism at dopamine D2 and serotonin 5-HT1A receptors and antagonism at serotonin 5-HT2A receptors. Aripiprazole has also received approval for the treatment of bipolar disorder as adjunctive therapy or monotherapy (manic or mixed episodes) as well as an augmentation therapy of major depressive disorder (MDD) by the US FDA. The overall safety and tolerability of aripiprazole is favorable compared to other atypical antipsychotics across the approved indications. Aripiprazole showed a minimal propensity for clinically significant weight gain and metabolic disruption. However, extrapyramidal side effects, such as akathisia, are reported and may limit its clinical use in some cases, particularly in patients with bipolar disorder and MDD. This review focuses on the tolerability and safety of aripiprazole across a broad spectrum of psychiatric disorders while taking into consideration results from registrational studies as well as findings from studies in the naturalistic setting. In conclusion, whereas the comparative safety and tolerability of aripiprazole has not been systematically evaluated in comparator studies, tolerability and safety issues commonly associated with atypical antipsychotics such as weight gain and metabolic syndrome are less prominent with aripiprazole.
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PMID:A review of the safety and tolerability of aripiprazole. 1950 66

The growing relevance of prostate carcinoma in the developed world requires serious attention to focus on the risk-benefit relationships of the treatments used. Given the increasingly complex therapeutic approach to prostate carcinoma, an extensive range of knowledge is required. Androgen deprivation plays a central role in this disease. The management of androgen deprivation-derived toxicity in the form of hot flashes, metabolic syndrome, osteoporosis, cognitive disorders, etc., is of growing interest. The drug treatment of hot flashes involves hormone management that is not without oncological risk and moreover generates considerable toxicity. Antidepressants in turn play an important role in the non-hormone treatment of this disorder. Trazodone, a serotonin reuptake inhibitor/5-HT2A receptor antagonist affording more selective action upon the receptors implicated in hot flashes, could be of great interest. Trazodone shows great affinity for the 5-HT2A receptors and moderate affinity for the 5-HT1A receptors. Serotonin (5-hydroxytryptamine, or 5-HT) levels are known to be lowered in postmenopausal women, and normalize when replacement therapy is provided. This suggests that abrupt sexual hormone deprivation gives rise to a reduction in blood serotonin - with a subsequent increase in its hypothalamic 5-HT2A receptors. These receptors would be implicated in the physiopathology of hot flashes; as a result, the blocking of such receptors is one of the principal therapeutic measures. The use of trazodone, increasing the serotonin concentrations and blocking the 5-HT2A and 5-HT1A receptors, could be viewed as a novel management approach more in line with the physiopathology of hot flashes. Well designed comparative studies are needed to establish the efficacy of such treatment. Other issues pending clarification would be the most effective dose and duration of treatment for controlling hot flashes.
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PMID:[Trazodone: a new selective approach to the treatment of hot flashes induced by androgen deprivation in prostate carcinoma?]. 1971 46

Patients with schizophrenia have a higher risk of developing metabolic abnormalities and their associated diseases. Some studies found that the accumulative number of metabolic syndrome components was associated with the severity of metabolic abnormalities. The purpose of this study was to examine the roles of the ADRA1A, ADRA2A, ADRB3, and 5HT2A genes in the risk of having more severe metabolic abnormalities among patients with schizophrenia. We studied a sample of 232 chronic inpatients with schizophrenia (120 males and 112 females) to explore the associations between the four candidate genes and the severity of metabolic syndrome by accumulative number of the components. Four single nucleotide polymorphisms in the candidate genes were genotyped, including the Arg347Cys in ADRA1A, the C1291G in ADRA2A, the Try64Arg in ADRB3, and the T102C in 5HT2A. An association between the accumulative number of metabolic syndrome components and the ADRA1A gene was found after adjusting age, sex, and other related variables (p-value=0.036). Presence of the Arg347 allele in the ADRA1A gene is a risk factor for having more severe metabolic abnormalities. These findings suggest a medical attention of closely monitoring metabolic risks for schizophrenia patients with high-risk genotypes.
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PMID:Association of the ADRA1A gene and the severity of metabolic abnormalities in patients with schizophrenia. 2203 78

Antipsychotics are frequently prescribed agents in individuals with intellectual disability, often for behavioral symptoms. Efficacy of antipsychotics for this is ambiguous, so discontinuation should be considered. Weight gain and metabolic dysregulation are well-known adverse effects of antipsychotics which increase the risk of the metabolic syndrome. We performed a discontinuation study in 99 adults with intellectual disability, living in residential facilities who used antipsychotics for behavioral symptoms for more than 1 year. The aim of the present study was to investigate the effects of discontinuation of long-term used antipsychotics on weight, body mass index (BMI), and parameters of the metabolic syndrome and to investigate the influence of genetic polymorphisms and medication factors on these outcomes. Discontinuation of antipsychotics led to a mean decrease of 4 cm waist circumference, of 3.5 kg weight, 1.4 kg/m2 BMI, and 7.1 mm Hg systolic blood pressure. In those participants who had not completely discontinued use of antipsychotics we found a decrease in weight and BMI and an increase in fasting glucose. The presence of the C-allele of serotonin 5-hydroxytryptamine receptor polymorphism rs141334 was associated with higher waist circumference and higher plasma levels of triglycerides and lower levels of high-density lipoprotein. Achievement of complete discontinuation predicted a larger decrease in waist circumference and BMI. In conclusion, results of the study show the beneficial effects of discontinuation of long-term used antipsychotics on metabolic outcomes.
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PMID:Effects of controlled discontinuation of long-term used antipsychotics on weight and metabolic parameters in individuals with intellectual disability. 2425 10

Despite recent success there remains a high therapeutic need for the development of drugs targeting diseases associated with the metabolic syndrome. As part of our search for safe and effective MCH-R1 antagonists for the treatment of obesity, a series of 3,6-disubstituted pyridazines was evaluated. During optimization several issues of the initial lead structures had to be resolved, such as selectivity over related GPCRs, inhibition of the hERG channel as well as the potential to induce phospholipidosis. Utilizing property-based design, we could demonstrate that all parameters can significantly be improved by consequently increasing the polarity of the compounds. By this strategy, we succeeded in identifying potent and orally available MCH-R1 antagonists with good selectivity over M1 and 5-HT2A and an improved safety profile with respect to hERG inhibition and phospholipidosis.
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PMID:Design, synthesis and evaluation of MCH receptor 1 antagonists--Part II: Optimization of pyridazines toward reduced phospholipidosis and hERG inhibition. 2607 92