Antipsychotic drug—aripiprazole against schizophrenia, its therapeutic and metabolic effects associated with gene polymorphisms

Stelmach, Adriana; Guzek, Katarzyna; Rożnowska, Alicja; Najbar, Irena; Sadakierska‐Chudy, Anna

doi:10.1007/s43440-022-00440-6

Cited by 11 publications

(3 citation statements)

References 105 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, novel medications, such as adenosine, histamine, and trace amine-associated receptor ligands, also function through the multimodal stimulatory mechanism of central serotonin, norepinephrine, and/or histamine neurotransmission [56]. The combination of antipsychotic and antidepressant medications has been suggested to work through the same mechanism of central monoamine neurotransmission, leading to a potential combined effect [38,57,58]. While APYs are often effective as monotherapies in treating bipolar patients, they are not as effective in treating unipolar depression.…”

Section: Apys As Adjuncts To Antidepressants Treat Schizophrenia and ...mentioning

confidence: 99%

Receptors Involved in Mental Disorders and the Use of Clozapine, Chlorpromazine, Olanzapine, and Aripiprazole to Treat Mental Disorders

et al. 2023

View full text Add to dashboard Cite

Mental illnesses are a global health challenge, and effective medicines are needed to treat these conditions. Psychotropic drugs are commonly prescribed to manage mental disorders, such as schizophrenia, but unfortunately, they can cause significant and undesirable side effects, such as myocarditis, erectile dysfunction, and obesity. Furthermore, some schizophrenic patients may not respond to psychotropic drugs, a condition called schizophrenia-treatment resistance. Fortunately, clozapine is a promising option for patients who exhibit treatment resistance. Unlike chlorpromazine, scientists have found that clozapine has fewer neurological side effects. Additionally, olanzapine and aripiprazole are well-known for their moderating effects on psychosis and are widely used in clinical practice. To further maximize drug efficacy, it is critical to deeply understand the receptors or signaling pathways central to the nervous system, such as serotonin, histamine, trace amines, dopamine, and G-protein coupled receptors. This article provides an overview of the receptors mentioned above, as well as the antipsychotics that interact with them, such as olanzapine, aripiprazole, clozapine, and chlorpromazine. Additionally, this article discusses the general pharmacology of these medications.

show abstract

Section: Apys As Adjuncts To Antidepressants Treat Schizophrenia and ...mentioning

confidence: 99%

Receptors Involved in Mental Disorders and the Use of Clozapine, Chlorpromazine, Olanzapine, and Aripiprazole to Treat Mental Disorders

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Modulation of serotonin and dopamine receptors in the central nervous system has proven to be an effective way to treat psychiatric disorders ( Malik et al, 2023 ; Stelmach et al, 2023 ). The dopamine receptor is the crucial target of all existing antipsychotics.…”

Section: Introductionmentioning

confidence: 99%

Assessing NH300094, a novel dopamine and serotonin receptor modulator with cognitive enhancement property for treating schizophrenia

Feng,

Hu,

et al. 2024

Front. Pharmacol.

View full text Add to dashboard Cite

Background: Schizophrenia is a serious psychiatric disorder that significantly affects the quality of life of patients. The objective of this study is to discover a novel antipsychotic candidate with highly antagonistic activity against both serotonin and dopamine receptors, demonstrating robust efficacy in animal models of positive, negative, and cognitive symptoms of schizophrenia.Methods: In the present study, we examined the activity of antipsychotic drug (NH300094) on 5-HT2A, 5-HT2C, 5-HT1A, 5-HT1B, 5-HT7, H1, M1, Alpha1A, D2L, D2S, Alpha2A, D3 receptor functional assay in vitro. In addition, multiple animal models, including dizocilpine (MK-801) induced hyper-locomotion; APO induced climbing; Conditioned Avoidance Response (CAR); DOI-Induced Head Twitch; Forced swimming test; Scopolamine induced cognitive impairment model, were used to verify the antipsychotic activity of NH300094 in preclinical.Results:In vitro functional assays have indicated that NH300094 is a potent antagonist of 5-HT receptors and dopamine receptors, with higher relative antagonistic activity against 5-HT2A receptor (5-HT2A IC50 = 0.47 nM) than dopamine receptors (D2L IC50 = 1.04 nM; D2S IC50 = 11.71 nM; D3 IC50 = 31.55 nM). Preclinical in vivo pharmacological study results showed that NH300094 was effective in multiple models, which is more extensive than the clinic drug Risperidone. Furthermore, the safety window for extrapyramidal side effects of NH300094 is significantly wider than that of Risperidone (For NH300094, mice catalepsy model ED50/ Mice MK-801 model ED50 = 104.6-fold; for Risperidone, mice catalepsy model ED50/ Mice MK-801 model ED50 = 12.9-fold), which suggests a potentially better clinical safety profile for NH300094.Conclusion: NH300094 is a novel potent serotonin and dopamine receptors modulator, which has good safety profile and therapeutic potential for the treatment of schizophrenia with cognition disorders.

show abstract

“…This debilitating disorder typically emerges at a young age, often before 18 years, and manifests a spectrum of symptoms, including positive, negative, and cognitive aspects. Managing schizophrenia remains a formidable challenge [9].…”

Section: Introductionmentioning

confidence: 99%

In Vitro/In VivoAssessment of Aripiprazole-Loaded Thiolated Arabinoxylan based Nanoparticles: An Innovative Approach for Targeted Schizophrenia Therapy

Sikander,

Tulain,

Malik

et al. 2024

Preprint

View full text Add to dashboard Cite

This study was conducted with the primary objective of improving the bioavailability of aripiprazole (APZ) through the development of nanoparticles using thiolated arabinoxylan (TAX) sourced from corn husk. TAX was synthesized via thiolation, employing thiourea as a thiol donor and hydrochloric acid as a catalyst. Characterization of TAX revealed a surface free thiol group content of 37.461 mmol/g, accompanied by an angle of repose measuring 0.393±0.035. Bulk density, tapped density, Hausner ratio, and Carr index fell within prescribed limits. Subsequently, APZ-loaded thiolated arabinoxylan based nanoparticles were fabricated using the ionotropic gelation method, with barium chloride serving as a cross-linker. Encapsulation efficiency was highest for formulation F4, at 97.1%±2.36. In vitro drug release demonstrated sustained release profiles at both pH 1.2 and pH 6.8, with F4 exhibiting the most favourable release kinetics. In vitro, characterization indicated that the optimized thiolated arabinoxylan based nanoparticle formulation had an average particle size of 211.1 nm with a Polydispersity Index (PDI) of 0.092 and a zeta potential of 0.621 mV. SEM imaging showed uniform, slightly spherical particles with minimal pores. DSC and TGA confirmed the conversion of APZ to amorphous states within the nanoparticles, enhancing solubility. Ex-vivo permeation studies exhibited favourable drug permeation. An In-vivo pharmacodynamics studies in a ketamine-induced schizophrenia rat model indicated the effectiveness of APZ loaded thiolated arabinoxylan based nanoparticles in behavioural tests, with no significant cataplectic effects observed. Acute oral toxicity assessments demonstrated the safety, with no mortality, no significant alterations in food and water consumption, or any histopathological abnormalities. In conclusion, these developed APZ-loaded thiolated arabinoxylan based nanoparticles hold promise for the effective treatment of schizophrenia without inducing toxic effects, showcasing their potential for clinical applications.

show abstract

Antipsychotic drug—aripiprazole against schizophrenia, its therapeutic and metabolic effects associated with gene polymorphisms

Cited by 11 publications

References 105 publications

Receptors Involved in Mental Disorders and the Use of Clozapine, Chlorpromazine, Olanzapine, and Aripiprazole to Treat Mental Disorders

Receptors Involved in Mental Disorders and the Use of Clozapine, Chlorpromazine, Olanzapine, and Aripiprazole to Treat Mental Disorders

Assessing NH300094, a novel dopamine and serotonin receptor modulator with cognitive enhancement property for treating schizophrenia

In Vitro/In VivoAssessment of Aripiprazole-Loaded Thiolated Arabinoxylan based Nanoparticles: An Innovative Approach for Targeted Schizophrenia Therapy

Contact Info

Product

Resources

About