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Journal of Psychiatric Research Jun 2024Variability in hepatic cytochrome P450 (CYP) enzymes such as 2C19 and 2D6 may influence side-effect and efficacy outcomes for antipsychotics. Aripiprazole and... (Review)
Review
Variability in hepatic cytochrome P450 (CYP) enzymes such as 2C19 and 2D6 may influence side-effect and efficacy outcomes for antipsychotics. Aripiprazole and risperidone are two commonly prescribed antipsychotics, metabolized primarily through CYP2D6. Here, we aimed to provide an overview of the effect of CYP2C19 and CYP2D6 on side-effects of aripiprazole and risperidone, and expand on existing literature by critically examining methodological issues associated with pharmacogenetic studies. A PRISMA compliant search of six electronic databases (Pubmed, PsychInfo, Embase, Central, Web of Science, and Google Scholar) identified pharmacogenetic studies on aripiprazole and risperidone. 2007 publications were first identified, of which 34 were included. Quality of literature was estimated using Newcastle-Ottowa Quality Assessment Scale (NOS) and revised Cochrane Risk of Bias tool. The average NOS score was 5.8 (range: 3-8) for risperidone literature and 5 for aripiprazole (range: 4-6). All RCTs on aripiprazole were rated as high risk of bias, and four out of six for risperidone literature. Study populations ranged from healthy volunteers to inpatient individuals in psychiatric units and included adult and pediatric samples. All n = 34 studies examined CYP2D6. Only one study genotyped for CYP2C19 and found a positive association with neurological side-effects of risperidone. Most studies did not report any relationship between CYP2D6 and any side-effect outcome. Heterogeneity between and within studies limited the ability to synthesize data and draw definitive conclusions. Studies lacked statistical power due to small sample size, selective genotyping methods, and study design. Large-scale randomized trials with multiple measurements, providing robust evidence on this topic, are suggested.
Topics: Humans; Aripiprazole; Cytochrome P-450 CYP2D6; Risperidone; Cytochrome P-450 CYP2C19; Antipsychotic Agents
PubMed: 38631139
DOI: 10.1016/j.jpsychires.2024.04.001 -
Scientific Reports Apr 2024Green spectrophotometric and HPLC methods have been developed for the quantification of metoclopramide. In the spectrophotometric method, it was determined by direct...
Green spectrophotometric and HPLC methods have been developed for the quantification of metoclopramide. In the spectrophotometric method, it was determined by direct absorbance measurement at 273 nm wavelength using ultrapure water as solvent. The Extend C18 column was used for the HPLC method. The mobile phase system consisted of a combination of ethanol and formic acid solution (pH 2.0; 30:70 v/v). Isocratic elution was applied and the flow rate was set at 1.0 mL min. Metoclopramide was detected at 273 nm. The methods performed were economical, rapid, environmentally friendly, and simple, providing metoclopramide analysis within 5 min. The methods have been successfully applied in pharmaceutical products without matrix interference. The results of the application of the developed methods to pharmaceutical products were statistically compared and no significant difference was observed between the methods. In addition, the greenness assessment of the developed methods was performed using AGREE software. Our developed methods, based on the use of solvents such as ethanol and water, are proposed as a more environmentally and analyst-friendly option for the quantification of metoclopramide in pharmaceutical products than other methods currently in use.
Topics: Chromatography, High Pressure Liquid; Metoclopramide; Ethanol; Water; Pharmaceutical Preparations
PubMed: 38627518
DOI: 10.1038/s41598-024-59149-6 -
IScience Apr 2024In this study, a murine sepsis model was developed using the cecum ligation and puncture (CLP) technique. The expression of the proinflammatory cytokines tumor necrosis...
In this study, a murine sepsis model was developed using the cecum ligation and puncture (CLP) technique. The expression of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) in the brain increased 6 h after CLP but decreased 24 h later when elevated endogenous dopamine levels in the brain were sustained. Methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride reduced dopamine levels in the striatum and increased mortality in septic mice. Dopamine D1-like receptors were significantly expressed in the brain, but not in the lungs. Intraperitoneally administered SKF-81297 (SKF), a blood-brain barrier-permeable D1-like receptor agonist, prevented CLP-induced death of septic mice with ameliorated acute lung injury and cognitive dysfunction and suppressed TNF-α and IL-1β expression. The D1-like receptor antagonist SCH-23390 abolished the anti-inflammatory effects of SKF. These data suggest that D1-like receptor-mediated signals in the brain prevent CLP-induced inflammation in both the brain and the periphery.
PubMed: 38623339
DOI: 10.1016/j.isci.2024.109587 -
Translational Neurodegeneration Apr 2024The renin-angiotensin system (RAS) was classically considered a circulating hormonal system that regulates blood pressure. However, different tissues and organs,... (Review)
Review
The renin-angiotensin system (RAS) was classically considered a circulating hormonal system that regulates blood pressure. However, different tissues and organs, including the brain, have a local paracrine RAS. Mutual regulation between the dopaminergic system and RAS has been observed in several tissues. Dysregulation of these interactions leads to renal and cardiovascular diseases, as well as progression of dopaminergic neuron degeneration in a major brain center of dopamine/angiotensin interaction such as the nigrostriatal system. A decrease in the dopaminergic function induces upregulation of the angiotensin type-1 (AT1) receptor activity, leading to recovery of dopamine levels. However, AT1 receptor overactivity in dopaminergic neurons and microglial cells upregulates the cellular NADPH-oxidase-superoxide axis and Ca release, which mediate several key events in oxidative stress, neuroinflammation, and α-synuclein aggregation, involved in Parkinson's disease (PD) pathogenesis. An intraneuronal antioxidative/anti-inflammatory RAS counteracts the effects of the pro-oxidative AT1 receptor overactivity. Consistent with this, an imbalance in RAS activity towards the pro-oxidative/pro-inflammatory AT1 receptor axis has been observed in the substantia nigra and striatum of several animal models of high vulnerability to dopaminergic degeneration. Interestingly, autoantibodies against angiotensin-converting enzyme 2 and AT1 receptors are increased in PD models and PD patients and contribute to blood-brain barrier (BBB) dysregulation and nigrostriatal pro-inflammatory RAS upregulation. Therapeutic strategies addressed to the modulation of brain RAS, by AT1 receptor blockers (ARBs) and/or activation of the antioxidative axis (AT2, Mas receptors), may be neuroprotective for individuals with a high risk of developing PD or in prodromal stages of PD to reduce progression of the disease.
Topics: Animals; Humans; Angiotensin Receptor Antagonists; Angiotensins; Blood Pressure; Brain; Dopamine; Parkinson Disease; Receptor, Angiotensin, Type 1; Renin-Angiotensin System
PubMed: 38622720
DOI: 10.1186/s40035-024-00410-3 -
Clinical Drug Investigation May 2024Schizophrenia is one of the leading causes of disability. Paliperidone palmitate once-monthly injection (PP1M) was developed to provide consistent drug delivery and...
Risk of Cardiovascular Events in Schizophrenic Patients Treated with Paliperidone Palmitate Once-Monthly Injection (PP1M): A Population-Based Retrospective Cohort Study in Taiwan.
BACKGROUND
Schizophrenia is one of the leading causes of disability. Paliperidone palmitate once-monthly injection (PP1M) was developed to provide consistent drug delivery and improve medication adherence for maintenance treatment. It is well known that patients with schizophrenia have higher cardiovascular risks, however little is known about the cardiovascular risks of patients with schizophrenia treated with PP1M in Asia.
OBJECTIVE
This study aimed to estimate the incidence of cardiovascular events after initiating PP1M treatment and evaluate the cardiovascular risk associations compared with oral second-generation antipsychotics (SGAs).
METHODS
Data from Taiwan's National Health Insurance Research Database were used to identify a cohort of adult patients with schizophrenia who received any SGAs from 1 March 2012 to 31 December 2018. Patients who initiated PP1M treatment were enrolled for descriptive analysis of incidence rates. PP1M patients were propensity matched 1:1 to patients initiating a new oral SGA, for comparative analysis based on demographics, clinical characteristics and treatment history at baseline, in three-step matching procedures, following the prevalent new-user design to enhance comparability. Follow-up ended at the end of the treatment episode of index drug, death, last record available, or end of the study (31 December 2019). Study endpoints included serious cardiovascular events (including severe ventricular arrhythmia and sudden death), expanded serious cardiovascular events (which further included acute myocardial infarction and ischemic stroke), and cardiovascular hospitalizations. Risks of study endpoints between matched cohorts were compared using Cox regression.
RESULTS
Overall, 11,023 patients initiating PP1M treatment were identified (49.5% were females; mean age of 43.2 [12.2] years). Overall incidences for serious cardiovascular events, expanded serious cardiovascular events, and cardiovascular hospitalizations were 3.92, 7.88 and 51.96 per 1000 person-years, respectively. In matched cohort analysis (N = 10,115), the hazard ratios (HRs) between initiating PP1M and a new oral SGA for serious cardiovascular events, expanded serious cardiovascular events, and cardiovascular hospitalizations were 0.86 (95% confidence interval [CI] 0.55-1.36), 0.88 (95% CI 0.63-1.21), and 0.78 (95% CI 0.69-0.89), respectively.
CONCLUSION
This study reported the population-based incidence of cardiovascular events in schizophrenic patients initiating PP1M treatment. PP1M was not associated with increased risks of serious cardiovascular events but was potentially associated with lower risks of cardiovascular hospitalizations compared with oral SGAs.
Topics: Humans; Schizophrenia; Female; Male; Paliperidone Palmitate; Taiwan; Retrospective Studies; Adult; Cardiovascular Diseases; Middle Aged; Antipsychotic Agents; Incidence; Injections
PubMed: 38619775
DOI: 10.1007/s40261-024-01358-y -
Disease Models & Mechanisms May 2024Dystonia is thought to arise from abnormalities in the motor loop of the basal ganglia; however, there is an ongoing debate regarding cerebellar involvement. We adopted...
Dystonia is thought to arise from abnormalities in the motor loop of the basal ganglia; however, there is an ongoing debate regarding cerebellar involvement. We adopted an established cerebellar dystonia mouse model by injecting ouabain to examine the contribution of the cerebellum. Initially, we examined whether the entopeduncular nucleus (EPN), substantia nigra pars reticulata (SNr), globus pallidus externus (GPe) and striatal neurons were activated in the model. Next, we examined whether administration of a dopamine D1 receptor agonist and dopamine D2 receptor antagonist or selective ablation of striatal parvalbumin (PV, encoded by Pvalb)-expressing interneurons could modulate the involuntary movements of the mice. The cerebellar dystonia mice had a higher number of cells positive for c-fos (encoded by Fos) in the EPN, SNr and GPe, as well as a higher positive ratio of c-fos in striatal PV interneurons, than those in control mice. Furthermore, systemic administration of combined D1 receptor agonist and D2 receptor antagonist and selective ablation of striatal PV interneurons relieved the involuntary movements of the mice. Abnormalities in the motor loop of the basal ganglia could be crucially involved in cerebellar dystonia, and modulating PV interneurons might provide a novel treatment strategy.
Topics: Animals; Interneurons; Parvalbumins; Disease Models, Animal; Proto-Oncogene Proteins c-fos; Dystonia; Corpus Striatum; Receptors, Dopamine D2; Receptors, Dopamine D1; Cerebellum; Ouabain; Mice, Inbred C57BL; Mice; Male
PubMed: 38616770
DOI: 10.1242/dmm.050338 -
Molecules (Basel, Switzerland) Mar 2024Nowadays, drug delivery systems (DDSs) are gaining more and more attention. Conducting polymers (CPs) are efficiently used for DDS construction as such systems can be...
Nowadays, drug delivery systems (DDSs) are gaining more and more attention. Conducting polymers (CPs) are efficiently used for DDS construction as such systems can be used in therapy. In this research, a well-known CP, polypyrrole (PPy), was synthesized in the presence of the polysaccharide heparin (HEP) and chlorpromazine (CPZ) using sodium dodecyl sulfate (SDS) as electrolyte on a steel substrate. The obtained results demonstrate the successful incorporation of CPZ and HEP into the polymer matrix, with the deposited films maintaining stable electrochemical parameters across multiple doping/dedoping cycles. Surface roughness, estimated via AFM analysis, revealed a correlation with layer thickness-decreasing for thinner layers and increasing for thicker ones. Moreover, SEM images revealed a change in the morphology of PPy films when PPy is electropolymerized in the presence of CPZ and HEP, while FTIR confirmed the presence of CPZ and HEP within PPy. Due to its lower molecular mass compared to HEP, CPZ was readily integrated into the thin polymer matrix during deposition, with diffusion being unimpeded, as opposed to films with greater thickness. Finally, the resulting system exhibited the ability to release CPZ, enabling a dosing range of 10 mg to 20 mg per day, effectively covering the therapeutic concentration range.
Topics: Polymers; Chlorpromazine; Pyrroles; Drug Delivery Systems; Heparin
PubMed: 38611809
DOI: 10.3390/molecules29071531 -
International Breastfeeding Journal Apr 2024A lack of safety data on postpartum medication use presents a potential barrier to breastfeeding and may result in infant exposure to medications in breastmilk. The type...
BACKGROUND
A lack of safety data on postpartum medication use presents a potential barrier to breastfeeding and may result in infant exposure to medications in breastmilk. The type and extent of medication use by lactating women requires investigation.
METHODS
Data were collected from the CHILD Cohort Study which enrolled pregnant women across Canada between 2008 and 2012. Participants completed questionnaires regarding medications and non-prescription medications used and breastfeeding status at 3, 6 and 12 months postpartum. Medications, along with self-reported reasons for medication use, were categorized by ontologies [hierarchical controlled vocabulary] as part of a large-scale curation effort to enable more robust investigations of reasons for medication use.
RESULTS
A total of 3542 mother-infant dyads were recruited to the CHILD study. Breastfeeding rates were 87.4%, 75.3%, 45.5% at 3, 6 and 12 months respectively. About 40% of women who were breastfeeding at 3 months used at least one prescription medication during the first three months postpartum; this proportion decreased over time to 29.5% % at 6 months and 32.8% at 12 months. The most commonly used prescription medication by breastfeeding women was domperidone at 3 months (9.0%, n = 229/2540) and 6 months (5.6%, n = 109/1948), and norethisterone at 12 months (4.1%, n = 48/1180). The vast majority of domperidone use by breastfeeding women (97.3%) was for lactation purposes which is off-label (signifying unapproved use of an approved medication). Non-prescription medications were more often used among breastfeeding than non-breastfeeding women (67.6% versus 48.9% at 3 months, p < 0.0001), The most commonly used non-prescription medications were multivitamins and Vitamin D at 3, 6 and 12 months postpartum.
CONCLUSIONS
In Canada, medication use is common postpartum; 40% of breastfeeding women use prescription medications in the first 3 months postpartum. A diverse range of medications were used, with many women taking more than one prescription and non-prescription medicines. The most commonly used prescription medication by breastfeeding women were domperidone for off-label lactation support, signalling a need for more data on the efficacy of domperidone for this indication. This data should inform research priorities and communication strategies developed to optimize care during lactation.
Topics: Infant; Female; Humans; Pregnancy; Breast Feeding; Lactation; Domperidone; Cohort Studies; Prospective Studies; Canada; Prescriptions
PubMed: 38589955
DOI: 10.1186/s13006-024-00628-x -
Case Reports in Psychiatry 2024This is a case report of three cases of trazodone-induced buccal-lingual dyskinesias. Each case demonstrated the distinct pattern of the development of this dyskinesia...
This is a case report of three cases of trazodone-induced buccal-lingual dyskinesias. Each case demonstrated the distinct pattern of the development of this dyskinesia after trazodone exposure for several months. All cases showed abrupt cessation of the movement disorder when the drug was discontinued. One of the three cases demonstrated a highly unusual presentation of an on/off pattern of buccal dyskinesia directly related to repetitive exposure and termination of the drug trazodone. Two of the three cases had no prior exposure to any dopamine blocking agents. One of the three had a distant exposure to a dopamine antagonist. As opposed to other antidepressants, trazodone has a mechanism of action which can account for both the development and treatment of dyskinetic movements. Its metabolite, M/chlorophenylpiperazine (M-CPP) is a 5HT2C agonist capable of causing abnormal oral-facial movements in rodent models. The presence of oromandibular dyskinetic movements can occur spontaneously with age, with trazodone being a potential predisposing factor. This article will discuss proposed mechanisms for trazodone's action with an emphasis on case reports of dystonic movements.
PubMed: 38585414
DOI: 10.1155/2024/5543023 -
Journal of Diabetes Apr 2024To summarize the clinical characteristics and imaging manifestations of patients with nonketotic hyperglycemic hemichorea (NH-HC) and to explore the possible...
OBJECTIVE
To summarize the clinical characteristics and imaging manifestations of patients with nonketotic hyperglycemic hemichorea (NH-HC) and to explore the possible pathogenesis, diagnosis. and treatment of the disease in order to improve the understanding of this disease and avoid misdiagnosis.
METHODS
Retrospective analysis was performed on the case data of five patients with NH-HC admitted to our hospital in recent years. The patients were treated in the department of endocrinology, department of neurology, and department of neurosurgery in our hospital, respectively. Meanwhile, relevant literatures were consulted for further learning.
RESULTS
NH-HC is usually presented as a triad of nonketotic hyperglycemia, lateral chorea, and typical imaging manifestations of head magnetic resonance imaging or computed tomography, but the clinical manifestations are not the same, and imaging features may also be different, presenting a diversified trend in clinical practice. All five patients were given glucose-lowering drugs and improved with or without combination of drugs to control symptoms of chorea.
CONCLUSION
NH-HC is a rare complication of diabetes, characterized by hyperglycemia and hemichorea. How to identify the extreme situation and make fast judgment is a top priority. Timely and correct control of blood glucose is the key to the treatment, and when necessary, application of dopamine receptor antagonists in patients with combination therapy can accelerate improvement of the clinical symptoms. The prognosis of NH-HC is good, the clinician should strengthen comprehensive understanding of this disease to avoid missed diagnosis or misdiagnosis and enable patients to get more timely and effective treatment.
Topics: Humans; Chorea; Retrospective Studies; Diabetes Mellitus; Hyperglycemia; Magnetic Resonance Imaging
PubMed: 38584150
DOI: 10.1111/1753-0407.13543