Molecular Mechanisms of Antipsychotic Drug-Induced Diabetes

Chen, Jiezhong; Huang, Xu‐Feng; Shao, Renfu; Chen, Chen; Deng, Chao

doi:10.3389/fnins.2017.00643

Cited by 66 publications

(56 citation statements)

References 144 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Smoking, obesity, and lower SES were associated with antipsychotic use also in our material. Use of S-GAs can affect normal glucose metabolism and induce weight gain by inhibiting the insulin signaling pathway which leads to insulin resistance and increased insulin production, or by direct damage to pancreatic beta cells [29]. During pregnancy, high maternal blood glucose results in increased fetal insulin production.…”

Section: Discussionmentioning

confidence: 99%

Second-generation antipsychotics and pregnancy complications

Ellfolk

Leinonen

Gissler

et al. 2019

Eur J Clin Pharmacol

View full text Add to dashboard Cite

Purpose To study if second-generation antipsychotic (S-GA) use during pregnancy is associated with an increased risk of pregnancy and neonatal complications. Methods A population-based birth cohort study using national register data extracted from the "Drugs and Pregnancy" database in Finland, years 1996-2016. The sampling frame included 1,181,090 pregnant women and their singleton births. Women were categorized into three groups: exposed to S-GAs during pregnancy (n = 4225), exposed to first-generation antipsychotics (F-GAs) during pregnancy (n = 1576), and unexposed (no purchases of S-GAs or F-GAs during pregnancy, n = 21,125). Pregnancy outcomes in S-GA users were compared with those in the two comparison groups using multiple logistic regression models. Results Comparing S-GA users with unexposed ones, the risk was increased for gestational diabetes (adjusted odds ratio, OR 1.43; 95% CI 1.25-1.65), cesarean section (OR 1.35; 95% CI 1.18-1.53), being born large for gestational age (LGA) (OR 1.57; 95% CI 1.14-2.16), and preterm birth (OR 1.29; 95% CI 1.03-1.62). The risk for these outcomes increased further with continuous S-GA use. Infants in the S-GA group were also more likely to suffer from neonatal complications. Comparing S-GA users with the F-GA group, the risk of cesarean section and LGAwas higher (OR 1.25, 95% CI 1.03-1.51; and OR 1.89, 95% CI 1.20-2.99, respectively). Neonatal complications did not differ between the S-GA and F-GA groups. Conclusions Prenatal exposure to S-GAs is associated with an increased risk of pregnancy complications related to impaired glucose metabolism. Neonatal problems are common and occur similarly in S-GA and F-GA users.

show abstract

Section: Discussionmentioning

confidence: 99%

Second-generation antipsychotics and pregnancy complications

Ellfolk

Leinonen

Gissler

et al. 2019

Eur J Clin Pharmacol

View full text Add to dashboard Cite

show abstract

“…Muscarinic M 3 receptor was an important receptor involved in antipsychotic‐induced diabetes, blockade of which on pancreatic β‐cells might decrease insulin secretion . As a matter of fact, olanzapine and clozapine with highest potency for M 3 receptor among antipsychotics had the highest risk to induce diabetes .…”

Section: Resultsmentioning

confidence: 99%

Continuation of structure–activity relationship study of novel benzamide derivatives as potential antipsychotics

Guo

Yang

et al. 2019

Archiv der Pharmazie

View full text Add to dashboard Cite

A series of benzamide derivatives possessing potent dopamine D 2 , serotonin 5-HT 1A , and 5-HT 2A receptor properties were synthesized and evaluated as potential antipsychotics. Among them, 5-(4-(4-(benzo[d]isothiazol-3-yl)piperazin-1-yl)butoxy)-N-cyclopropyl-2-fluorobenzamide (4k) held the best pharmacological profile. It not only exhibited potent and balanced activities for the D 2 , 5-HT 1A , and 5-HT 2A receptors, but was also endowed with low to moderate activities for the 5-HT 2C , H 1 , and M 3 receptors, suggesting a low propensity for inducing weight gain or diabetes. In animal models, compound 4k reduced phencyclidine-induced hyperactivity with a high threshold for catalepsy or muscle relaxation induction. On the basis of its robust in vitro potency and in vivo efficacy in preclinical models of schizophrenia, 4k was selected as a candidate for further development. K E Y W O R D S 5-HT 1A , 5-HT 2A , catalepsy, D 2 , PCP-induced hyperactivity

show abstract

“…Metabolic disorders such as weight gain, insulin resistance and diabetes are common and serious side-effects of antipsychotics, especially for atypical antipsychotic drugs [6,8]. A recent meta-analysis in 25 studies with 154,718 schizophrenia and 4,343,407 control subjects showed antipsychotic treatment led to 2.5 times higher risk of type 2 diabetes (T2D) [33].…”

Section: Bdnf Val66met Polymorphism and Metabolic Disordersmentioning

confidence: 99%

BDNF as a pharmacogenetic target for antipsychotic treatment of schizophrenia

Han

Deng

2020

Neuroscience Letters

Self Cite

View full text Add to dashboard Cite

Antipsychotic drugs remain the mainstay of pharmacotherapy for schizophrenia. As there are large individual variations in efficacy and side-effects of antipsychotic drugs, there is a strong demand for personalized medication to treat schizophrenia. Pharmacogenetic research into antipsychotic drugs has examined a number of genetic variants and only a few polymorphisms have been found which promise to be associated with the therapeutic efficacy and side-effects of antipsychotic drugs. Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a major role in neurogenesis and neuroplasticity, and in the modulation of several neurotransmitter systems including the dopaminergic system involved in the pathophysiology of schizophrenia. This review focused on the association between the BDNF gene Val66Met polymorphism and antipsychotic drugs. The BDNF Val66Met polymorphism has been related to the pathophysiology of schizophrenia, psychotic symptomatology, cognition, efficacy and side-effects of antipsychotic drugs. The BDNF Val66Met variants could be a promising target for antipsychotic medication options or developing next generation antipsychotic drugs. However, some studies showed inconsistent results due to sample size, ethnic differences and different antipsychotic drugs. Further studies will be required in this area to confirm the effect of the BDNF Val66Met polymorphism in the pathophysiology of schizophrenia and patients' response to antipsychotic drugs, especially in a larger sample size and in different ethnic populations.

show abstract

Molecular Mechanisms of Antipsychotic Drug-Induced Diabetes

Cited by 66 publications

References 144 publications

Second-generation antipsychotics and pregnancy complications

Second-generation antipsychotics and pregnancy complications

Continuation of structure–activity relationship study of novel benzamide derivatives as potential antipsychotics

BDNF as a pharmacogenetic target for antipsychotic treatment of schizophrenia

Contact Info

Product

Resources

About