Current Concepts and Treatments of Schizophrenia
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 a...
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-08-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/23/8/2087 |
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| author | Piotr Stępnicki Magda Kondej Agnieszka A. Kaczor |
| author_facet | Piotr Stępnicki Magda Kondej Agnieszka A. Kaczor |
| author_sort | Piotr Stępnicki |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T13:01:11Z |
| format | Article |
| id | doaj.art-caec0a156415439ba993471ef694af34 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-12T13:01:11Z |
| publishDate | 2018-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-caec0a156415439ba993471ef694af342022-12-22T00:23:47ZengMDPI AGMolecules1420-30492018-08-01238208710.3390/molecules23082087molecules23082087Current Concepts and Treatments of SchizophreniaPiotr Stępnicki0Magda Kondej1Agnieszka A. Kaczor2Department of Synthesis and Chemical Technology of Pharmaceutical Substances, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 4A Chodzki St., PL-20093 Lublin, PolandDepartment of Synthesis and Chemical Technology of Pharmaceutical Substances, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 4A Chodzki St., PL-20093 Lublin, PolandDepartment of Synthesis and Chemical Technology of Pharmaceutical Substances, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 4A Chodzki St., PL-20093 Lublin, PolandSchizophrenia 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.http://www.mdpi.com/1420-3049/23/8/2087antipsychoticsdopaminedrug designdrug targetsschizophrenia |
| spellingShingle | Piotr Stępnicki Magda Kondej Agnieszka A. Kaczor Current Concepts and Treatments of Schizophrenia Molecules antipsychotics dopamine drug design drug targets schizophrenia |
| title | Current Concepts and Treatments of Schizophrenia |
| title_full | Current Concepts and Treatments of Schizophrenia |
| title_fullStr | Current Concepts and Treatments of Schizophrenia |
| title_full_unstemmed | Current Concepts and Treatments of Schizophrenia |
| title_short | Current Concepts and Treatments of Schizophrenia |
| title_sort | current concepts and treatments of schizophrenia |
| topic | antipsychotics dopamine drug design drug targets schizophrenia |
| url | http://www.mdpi.com/1420-3049/23/8/2087 |
| work_keys_str_mv | AT piotrstepnicki currentconceptsandtreatmentsofschizophrenia AT magdakondej currentconceptsandtreatmentsofschizophrenia AT agnieszkaakaczor currentconceptsandtreatmentsofschizophrenia |