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Review
. 2018 Aug 20;23(8):2087.
doi: 10.3390/molecules23082087.

Current Concepts and Treatments of Schizophrenia

Piotr Stępnicki  1 , Magda Kondej  2 , Agnieszka A Kaczor  3   4
Affiliations
Review

Current Concepts and Treatments of Schizophrenia

Piotr Stępnicki et al. Molecules. .

Abstract

Schizophrenia is a debilitating mental illness which involves three groups of symptoms, i.e., positive, negative and cognitive, and has major public health implications. According to various sources, it affects up to 1% of the population. The pathomechanism of schizophrenia is not fully understood and current antipsychotics are characterized by severe limitations. Firstly, these treatments are efficient for about half of patients only. Secondly, they ameliorate mainly positive symptoms (e.g., hallucinations and thought disorders which are the core of the disease) but negative (e.g., flat affect and social withdrawal) and cognitive (e.g., learning and attention disorders) symptoms remain untreated. Thirdly, they involve severe neurological and metabolic side effects and may lead to sexual dysfunction or agranulocytosis (clozapine). It is generally agreed that the interactions of antipsychotics with various neurotransmitter receptors are responsible for their effects to treat schizophrenia symptoms. In particular, several G protein-coupled receptors (GPCRs), mainly dopamine, serotonin and adrenaline receptors, are traditional molecular targets for antipsychotics. Comprehensive research on GPCRs resulted in the exploration of novel important signaling mechanisms of GPCRs which are crucial for drug discovery: intentionally non-selective multi-target compounds, allosteric modulators, functionally selective compounds and receptor oligomerization. In this review, we cover current hypotheses of schizophrenia, involving different neurotransmitter systems, discuss available treatments and present novel concepts in schizophrenia and its treatment, involving mainly novel mechanisms of GPCRs signaling.

Keywords: antipsychotics; dopamine; drug design; drug targets; schizophrenia.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The chemical structures of representatives of second-generation antipsychotic drugs.
Figure 2
Figure 2
Antipsychotic drugs categorized as the third generation and their structures.
Figure 3
Figure 3
Allosteric modulators of dopamine D2 receptor with possible application for the treatment of schizophrenia.
See this image and copyright information in PMC

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