Next-generation antipsychotics- Trends and perspectives beyond dopaminergic and glutamatergic agents

Introduction Three generations of antipsychotics, all which are based on the dopaminergic hypothesis schizophrenia, available for clinical use. Still, more than 66% patients diagnosed with schizophrenia spectrum disorders (SSD) could not achieve remission. Also, glutamatergic is supported by translational models this disease, even if antipsychotics derived from conceptual framework yet market. However, need new pathogenesis and acute, therefore, an exploration in pipeline be helpful understanding current stage research schizophrenia. Objectives To assess evidence supporting potential benefits pipeline. Methods A literature review was performed through main electronic databases PubMed, Cochrane, Clarivate/Web Of Science, EMBASE) trials repositories (US National Library Medicine World Health Organization Clinical Trials Registry Platform) using search paradigm “antipsychotics” AND “schizophrenia” “non-dopaminergic” “non-glutamatergic”. All papers published between January 2010 September 2022 were included. Results Xanomeline/trospium (xanomeline a muscarinic M1/M4 receptor agonist at central nervous system, while trospium limits its peripheral effects) efficient one phase III trial. Pimavanserin (a selective 5HT2A inverse antagonist) improving negative symptoms II Roluperidone σ2 has been associated favorable results trials, mainly SEP-363856 TAAR-1 5HT1A agonist, currently explored MK-8189 phosphodiesterase 10A inhibitor, investigated Conclusions Based retrieved data literature, multiple mechanisms, other pathways, being investigated, many these mechanisms advanced research. This important only to find tolerable drugs but also because they may shed light disease. Disclosure Interest None Declared