Update on Oxytocin, Phosphodiesterase, Neurokinin, Glycine as a Therapeutic Approach in the Treatment of Schizophrenia.

BACKGROUND: Schizophrenia is a chronic psychiatric disorder characterized by disrupted thoughts, perception, mood, and behavior. It has a heterogeneous genetic and neurobiological background and affects about 0.5-1% of the adult population worldwide. Herein, we review the current approaches and advances in schizophrenia. The potential therapeutic compounds for the treatment of schizophrenia act on the oxytocin receptor, phosphodiesterase system, neurokinin receptor, and glycine transport 1 receptor. Therefore, this article provides an update on the pharmacology of different receptors in addition to the dopaminergic system. These findings would guide the readers on novel targets for schizophrenia with the potential to be therapeutic agents in the future. OBJECTIVE: To provide the researchers an update on the emerging role of oxytocin, phosphodiesterase, neurokinin, and glycine which can be explored as potential pharmacotherapeutic targets in the treatment of schizophrenia. METHODS: An extensive literature search was conducted using PubMed, Science Direct, and NCBI with the following keywords: schizophrenia, novel receptors, oxytocin, phosphodiesterase, neurokinin, and glycine. Furthermore, to provide insights into newer drug treatments for Schizophrenia, Furthermore, Clinicaltrials.gov website was searched for newer receptor-based drugs. RESULTS: Current literature supported by preclinical and clinical provides substantial evidence that oxytocin, phosphodiesterase, neurokinin, and glycine play a crucial role in Schizophrenia. CONCLUSION: Our findings indicate that though multiple antipsychotic drugs are prescribed to treat schizophrenia, novel approaches and/or mechanisms are plausible. Moreover, sensitive and specific diagnostic tools and safe and effective interventions, including novel therapeutic agents, are required to yield substantially improved future outcomes.

Use of In silico tools for screening buffers to overcome physical instability of Abatacept.

Rheumatoid arthritis is an autoimmune disorder. Abatacept (CTLA4-Ig) is used for the treatment of Rheumatoid arthritis. Abatacept is a monoclonal antibody. Monoclonal antibodies undergo chemical (e.g. oxidation, deamidation, hydrolysis) and physical (e.g. aggregation, unfolding) instabilities while handling and storage. Abatacept is also prone to aggregation. Stabilizing agents such as buffers are used to stabilize monoclonal antibodies. But, the selection of the appropriate buffer is a time-consuming process because after testing many buffers based on the analysis of the results the appropriate buffer is identified. To overcome this issue in the current study computational tools were utilized to virtually screen different buffers to select the appropriate buffer. Ligand binding is the principal mechanism of conformational stability of proteins. For the buffers as well ligand binding is the most common mechanism for enhancing the thermodynamic stability of proteins. Generally it is observed that by enhancing the thermodynamic stability there is reduction in the rate of aggregation of proteins. Buffer (ligand) binds to the native state of the protein preferentially; it results in stabilization of the protein, while in the case of denatured protein it has no impact. There are many studies conducted involving the proteins in buffer solutions but very limited information is available about the mechanism of protein-buffer interactions. In the current study ligand binding mechanism of protein - buffer interaction was studied using molecular docking. After the docking buffers were ranked according to their energy value. The lower energy scores represent better protein-buffer (ligand) binding affinity compared to high energy values. It was observed that Phosphate with a binding affinity of -107.9 kcal/mol was the buffer with the least binding energy followed by Citrate (-70.6 kcal/mol), Melglumine (-66.6 kcal/mol), Arginine (-64.5 kcal/mol), Glucono delta lactone (-62.6 kcal/mol), Sodium citrate (-56.5 kcal/mol), Tromethamine (-52.3 kcal/mol), Glycine HCl (-37.2 kcal/mol), Sulfuric acid (-37.7 kcal/mol), Ammonium acetate (-31.1 kcal/mol), Acetic acid (-30.7 kcal/mol). With lower binding energy higher is the affinity between the ligand and protein. So phosphate was identified as a buffer with the highest affinity with Abatacept.