Development of novel antipsychotic agents by inhibiting dopamine transporter – in silico approach

Dopamine transporter inhibition is deemed a promising schizophrenia treatment approach. This research paper outlines various QSAR modeling for molecules acting as dopamine transporter inhibitors. The SMILES notation and the local...

Innovative Method Development Comprehensive Separation of Impurities and Validation for a novel Antipsychotic Drug Blonanserin

Blonanserin an antipsychotic novel drug used for the treatment of schizophrenia has antagonist properties for dopamine D2 and serotonin 5-HT2. On the other hand, it lacks adrenergic-α1, muscarinic M1, and histamine H1 antagonist activities. Clinical studies demonstrated in Japan had shown to be more effective for treating negative as well as positive schizophrenic symptoms. This drug was accepted and approved worldwide in the treatment of schizophrenia. A new HPLC method was developed and validated for the estimation of Impurities of Blonanserin (BNS) to ensure that the methodology meets the requirements of the target analysis application. Active and efficient chromatographic separation was achieved on a Zorbax Bonus RP EP C18 column having a particle size of 5μm, with dimensions of 250mm × 4.6 mm, mobile phase containing pH 2.4 buffer and Organic, with 1.0 ml /min flow rate, column oven temperature at 30oC and the eluent detection at 245 nm. The method shows well-separated impurities, is specific without interference from blank solution with resolution more than 1.2 between any of the impurity, correlation coefficient more than 0.99 showing good linearity; mean recovery ranging from 97% to 105% and is very sensitive at lower detection and quantification limits. This method was well developed and has been applied successfully to monitor and estimate impurities in Blonanserin.

Schizophrenia: Epidemiology, Causes, Neurobiology, Pathophysiology, and Treatment

Schizophrenia is a severe mental illness that has devastating consequences for those who suffer from the disorder. The epidemiology of schizophrenia indicates that it occurs relatively often, in many different contexts, and in conjunction with other disorders, decreasing quality of life and causing premature death. There has been an enormous amount of research into the causes of schizophrenia and there is now have a much better understanding of the genetic, environmental, and psychological factors that contribute to the disease. While there are numerous ways to understand and conceptualize schizophrenia, a unified picture of the neurobiology, changes in brain structure, cognitive and social-cognitive impairments related to the disorder has yet to emerge. Convulsive therapies and psychosurgery were used unsuccessfully, indiscriminately and without scientific validation in the past to treat schizophrenia. Medical advances including advanced imaging technology have now provided the ability to perform specifically focused neuromodulation and psychosurgery in severe and treatment resistant cases of schizophrenia. While still at a preliminary stage, these approaches have the potential to yield effective treatments in the future. For the last 70 years antipsychotic medication has become the prevailing treatment for schizophrenia. However, many people suffering from the disorder have trouble with side-effects and adhering to a regimen of antipsychotic medication. Newer pharmacological agents are being developed and include not only novel antipsychotic drugs, but anti-inflammatory and immunomodulating agents as well. These new agents, used either alone or in combination, have the potential to improve outcomes for people suffering from schizophrenia. Nevertheless, conclusively better pharmacotherapies will likely not arise until there is better understanding of the pathophysiology underlying schizophrenia. After the development of antipsychotic medication, psychotherapeutic methods for treating schizophrenia fell out of favor, but there is currently some reversal of this trend. The use of newer psychotherapies and modified forms of older therapeutic treatments are not only targeting the symptoms of schizophrenia but are also now focusing on recovery from the disorder. These newer approaches as well as efforts at preventing schizophrenia show promise in reducing the suffering caused by this disease.

The Novel Antipsychotic Drug Cariprazine and Cognition Enhancing Drugs: Indications for Their Use as an Add-on Therapy in Schizophrenia

Background: Schizophrenia and schizoaffective disorder are treated with antipsychotic drugs. Some patients show treatment-resistant forms of psychotic disorders and, in this case, they can be treated with clozapine. In these patients and based on previous reviews on novel antipsychotic drugs, it is important to know whether an add-on therapy with new drugs can ameliorate the positive and negative schizophrenic scale (PANSS) total score. Objective: The aim of this review is to suggest an appropriate treatment for patients with treatment-resistant forms of psychotic disorders. A combination of current available antipsychotic drugs with novel antipsychotic or modulating drugs might improve negative schizophrenic symptoms and cognitive function and thereby social functioning and quality of life. Results: The mechanisms of action, the therapeutic effects and the pharmacokinetic profiles of novel antipsychotic drugs such as cariprazine, brexipiprazole and lumateperone are up-dated. Published case reports of patients with treatmentresistant psychoses are also discussed. These patients were treated with clozapine but a high PANSS total score was observed. Only an add-on therapy with cariprazine improved the score and, above all, negative schizophrenic symptoms and cognitive functions. To ensure a constant antipsychotic drug concentration, long-acting injectable antipsychotic drugs may be a choice for a maintenance therapy in schizophrenia. New modulating drugs, such as receptor positive allosteric modulators (N-methyl-D-aspartate receptor; subtype 5 of the metabotropic glutamatergic receptor) and encenicline, an alpha7 nicotinic cholinergic receptor agonist, are being investigated in preclinical and clinical trials. Conclusion: In clinical trials, patients with treatment-resistant forms of psychosis should be examined to know whether a combination therapy with clozapine and a novel antipsychotic drug can ameliorate the PANSS total score. In schizophrenia, long-acting injectable antipsychotic drugs are a safe and tolerable maintenance therapy. In further clinical studies, it should be investigated whether patients with treatment-resistant forms of psychoses can improve negative schizophrenic symptoms and cognitive functions by an add-on therapy with cognition enhancing drugs.