The Secure Therapeutic Effects of Recently Developed Antipsychotic Drugs and Updated Neural Networks in Schizophrenia

Schizophrenia and schizoaffective disorder are treated in most cases with antipsychotic drugs of the second generation. These drugs block dopaminergic and serotonergic receptors, i.e., D2 and 5-HT2A receptors, and cause different adverse effects, for example, movement disturbances of the extrapyramidal system and adverse effects of vital parameters and of the heart. These drugs treat positive symptoms in schizophrenia and, to a lesser extent, negative symptoms. This review presents the development of newer antipsychotic drugs. References were taken from PubMed after using the following keywords: schizophrenia, schizoaffective disorder, antipsychotic drug, neurotransmitter and neuropeptide. Among these newer antipsychotic drugs are cariprazine, brexipiprazole and lumateperone, which exert a partial agonistic effect at D2 and 5-HT2A receptors, pimavanserin, a 5-HT2A receptor antagonist which treats negative symptoms in schizophrenia as add-on therapy, olanzapine combined with samidorphan, which reduces weight gain, and M4 or M1 receptor agonists, for example, xanomeline with an antipsychotic effect combined with trospium, an anticholinergic drug. Neural networks were updated in order to deduce the antipsychotic mechanism of action of newer antipsychotic drugs, especially xanomeline. The newer antipsychotic drugs cariprazine, brexipiprazole and lumateperone show antipsychotic, antimanic and anti-depressive effects, however, the efficacy on psychotic symptoms in long-term treatment has not yet been examined. Pimavanserin reduces negative symptoms in schizophrenia as an additional pharmacotherapy to treat this disorder. Olanzapine combined with samidorphan exerts good antipsychotic effects and reduces weight gain. The new antipsychotic drug xanomeline, the antipsychotic effect of which is quite different from the antidopaminergic effect, treats positive and negative symptoms in schizophrenia. Its mechanism of action was deduced from the neural networks presented. The long-term efficacy should still be examined. This review is focused on newer antipsychotic drugs. The long-term efficacy of cariprazine, brexipiprazole and lumateperone in the treatment of schizophrenia should be examined further. Neural networks in the brain areas involved in schizophrenia should be examined and updated furthermore. Newer antipsychotic drugs ,for example, xanomeline, an M4 or M1 receptor agonist, which has been combined with trospium, an anticholinergic drug, the mechanism of action of which can be derived from the neural network suggested in this review.