Pub Date : 2026-01-08DOI: 10.1038/s41573-025-01335-w
Joseph T Coyle, Steven M Paul
Until very recently, every drug approved for the treatment of schizophrenia over the past 70 years had the primary mechanism of directly or indirectly antagonizing dopamine D2 receptor activation. The role of dopamine as a critical mediator of psychosis is well established, and psychotic symptoms such as hallucinations and delusions are key features of schizophrenia. However, other important symptoms, including negative symptoms such as social withdrawal and anhedonia, and cognitive impairments, are largely unaffected by current antipsychotic drugs, resulting in the persistent disability of most individuals with schizophrenia. Schizophrenia also results in premature death due to a high prevalence of cardiovascular disease that can be exacerbated by current antipsychotic medications. Advances in our understanding of the genetics and pathophysiology of schizophrenia demonstrate that the disorder is complex with numerous underlying aetiologies, indicating that a single drug is unlikely to affect all aspects of the disorder. The recent approval of the M1/M4 muscarinic acetylcholine receptor agonist xanomeline/trospium chloride has begun to expand the therapeutic toolbox for schizophrenia. This Review covers promising drug targets for schizophrenia treatment that impact neurotransmitter systems, immune processes and inflammation. Despite failed clinical trials of some agents with novel mechanisms, several have recently been shown to improve one or more symptom domains of schizophrenia, suggesting that these targets may lead to more effective treatments.
{"title":"Novel drug treatments for schizophrenia.","authors":"Joseph T Coyle, Steven M Paul","doi":"10.1038/s41573-025-01335-w","DOIUrl":"https://doi.org/10.1038/s41573-025-01335-w","url":null,"abstract":"<p><p>Until very recently, every drug approved for the treatment of schizophrenia over the past 70 years had the primary mechanism of directly or indirectly antagonizing dopamine D<sub>2</sub> receptor activation. The role of dopamine as a critical mediator of psychosis is well established, and psychotic symptoms such as hallucinations and delusions are key features of schizophrenia. However, other important symptoms, including negative symptoms such as social withdrawal and anhedonia, and cognitive impairments, are largely unaffected by current antipsychotic drugs, resulting in the persistent disability of most individuals with schizophrenia. Schizophrenia also results in premature death due to a high prevalence of cardiovascular disease that can be exacerbated by current antipsychotic medications. Advances in our understanding of the genetics and pathophysiology of schizophrenia demonstrate that the disorder is complex with numerous underlying aetiologies, indicating that a single drug is unlikely to affect all aspects of the disorder. The recent approval of the M<sub>1</sub>/M<sub>4</sub> muscarinic acetylcholine receptor agonist xanomeline/trospium chloride has begun to expand the therapeutic toolbox for schizophrenia. This Review covers promising drug targets for schizophrenia treatment that impact neurotransmitter systems, immune processes and inflammation. Despite failed clinical trials of some agents with novel mechanisms, several have recently been shown to improve one or more symptom domains of schizophrenia, suggesting that these targets may lead to more effective treatments.</p>","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":" ","pages":""},"PeriodicalIF":101.8,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145934524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-05DOI: 10.1038/d41573-025-00209-5
Katie Kingwell
{"title":"Promoting prostaglandin signalling for joint repair in osteoarthritis","authors":"Katie Kingwell","doi":"10.1038/d41573-025-00209-5","DOIUrl":"10.1038/d41573-025-00209-5","url":null,"abstract":"","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"25 2","pages":"94-94"},"PeriodicalIF":101.8,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145903016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-02DOI: 10.1038/d41573-026-00001-z
Asher Mullard
The US FDA approved 46 new drugs in 2025, despite a tumultuous year at the regulatory agency. The US FDA approved 46 new drugs in 2025, despite a tumultuous year at the regulatory agency.
{"title":"2025 FDA approvals","authors":"Asher Mullard","doi":"10.1038/d41573-026-00001-z","DOIUrl":"10.1038/d41573-026-00001-z","url":null,"abstract":"The US FDA approved 46 new drugs in 2025, despite a tumultuous year at the regulatory agency. The US FDA approved 46 new drugs in 2025, despite a tumultuous year at the regulatory agency.","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"25 2","pages":"81-87"},"PeriodicalIF":101.8,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-17DOI: 10.1038/d41573-025-00207-7
Asher Mullard
{"title":"FDA approves first gene therapy from a non-profit organization, but pricing and access questions remain","authors":"Asher Mullard","doi":"10.1038/d41573-025-00207-7","DOIUrl":"10.1038/d41573-025-00207-7","url":null,"abstract":"","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"25 2","pages":"88-88"},"PeriodicalIF":101.8,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145771363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-12DOI: 10.1038/d41573-025-00206-8
Asher Mullard
The WNT–β-catenin pathway is often overactive in cancer. Can emerging drugs — including stabilized peptides, condensate modulators and degraders — safely and effectively tamp it back down? The WNT–β-catenin pathway is often overactive in cancer. Can emerging drugs — including stabilized peptides, condensate modulators and degraders — safely and effectively tamp it back down?
{"title":"Betting on β-catenin inhibitors in oncology","authors":"Asher Mullard","doi":"10.1038/d41573-025-00206-8","DOIUrl":"10.1038/d41573-025-00206-8","url":null,"abstract":"The WNT–β-catenin pathway is often overactive in cancer. Can emerging drugs — including stabilized peptides, condensate modulators and degraders — safely and effectively tamp it back down? The WNT–β-catenin pathway is often overactive in cancer. Can emerging drugs — including stabilized peptides, condensate modulators and degraders — safely and effectively tamp it back down?","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"25 1","pages":""},"PeriodicalIF":101.8,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145732678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-12DOI: 10.1038/d41573-025-00205-9
Asher Mullard
Philip Kym, Calico’s new head of drug discovery, talks about drugging ageing and ageing-related diseases. Philip Kym, Calico’s new head of drug discovery, talks about drugging ageing and ageing-related diseases.
{"title":"Calico, Alphabet’s anti-ageing play, goes it alone","authors":"Asher Mullard","doi":"10.1038/d41573-025-00205-9","DOIUrl":"10.1038/d41573-025-00205-9","url":null,"abstract":"Philip Kym, Calico’s new head of drug discovery, talks about drugging ageing and ageing-related diseases. Philip Kym, Calico’s new head of drug discovery, talks about drugging ageing and ageing-related diseases.","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"25 1","pages":"14-15"},"PeriodicalIF":101.8,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/d41573-025-00205-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145732680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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