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CB1 receptor antagonists: new discoveries leading to new perspectives

2012; Wiley; Volume: 205; Issue: 1 Linguagem: Inglês

10.1111/j.1748-1716.2012.02402.x

1748-1716

Eszter Kirilly, Xénia Gonda, György Bagdy,

Pancreatic function and diabetes

Acta PhysiologicaVolume 205, Issue 1 p. 41-60 REVIEW CB1 receptor antagonists: new discoveries leading to new perspectives E. Kirilly, E. Kirilly Department of Pharmacodynamics, Semmelweis University, Budapest, HungarySearch for more papers by this authorX. Gonda, X. Gonda Department of Clinical and Theoretical Mental Health, Kútvölgyi Clinical Center, Semmelweis University, Budapest, HungarySearch for more papers by this authorG. Bagdy, Corresponding Author G. Bagdy Department of Pharmacodynamics, Semmelweis University, Budapest, Hungary Group of Neurochemistry, Semmelweis University and Hungarian Academy of Sciences, Budapest, Hungary Group of Neuropsychopharmacology, Semmelweis University and Hungarian Academy of Sciences, Budapest, Hungary Correspondence: Prof. G. Bagdy, Chairman, Department of Pharmacodynamics, Semmelweis University, Nagyvarad ter 4, 1089 Budapest, Hungary. E-mail: [email protected]Search for more papers by this author E. Kirilly, E. Kirilly Department of Pharmacodynamics, Semmelweis University, Budapest, HungarySearch for more papers by this authorX. Gonda, X. Gonda Department of Clinical and Theoretical Mental Health, Kútvölgyi Clinical Center, Semmelweis University, Budapest, HungarySearch for more papers by this authorG. Bagdy, Corresponding Author G. Bagdy Department of Pharmacodynamics, Semmelweis University, Budapest, Hungary Group of Neurochemistry, Semmelweis University and Hungarian Academy of Sciences, Budapest, Hungary Group of Neuropsychopharmacology, Semmelweis University and Hungarian Academy of Sciences, Budapest, Hungary Correspondence: Prof. G. Bagdy, Chairman, Department of Pharmacodynamics, Semmelweis University, Nagyvarad ter 4, 1089 Budapest, Hungary. E-mail: [email protected]Search for more papers by this author First published: 26 December 2011 https://doi.org/10.1111/j.1748-1716.2011.02402.xCitations: 51Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract CB1 receptor antagonists were among the most promising drug targets in the last decade. They have been explored and found to be effective as therapeutic agents for obesity and related cardiometabolic problems; however, use of rimonabant, the first marketed CB1 receptor antagonist, has been suspended because of its anxiogenic and depressogenic side effects. Because some other antiobesity drugs, like dexfenfluramine or sibutramine, were also suspended, the unmet need for drugs that reduce body weight became enormous. One approach that emerged was the use of CB1 receptor antagonists that poorly cross the blood brain barrier, the second, the development of neutral antagonists instead of inverse agonists, and the third, use of personalized medicine, namely the selection of the patient population without psychiatric side effects. In this review, we dissect the peripheral and central mechanisms involved in the effects of CB1 receptor antagonists and argue that central mechanisms are more or less involved in most cardiometabolic therapeutic effects and thus, among patients with unsatisfactory therapeutic response to compounds with peripheral action, centrally acting antagonists may be needed. An analysis of pharmacogenetic factors may help to identify persons who are at no or low risk for psychiatric adverse effects. 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