Building better strategies to develop new medications in Alcohol Use Disorder: Learning from past success and failure to shape a brighter future

NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS

卷:103

Review

Cannella, Nazzareno¹  Ubaldi, Massimo¹  Masi, Alessio¹  Bramucci, Massimo¹  Roberto, Marisa²  Bifone, Angelo^3,4  Ciccocioppo, Roberto¹ 

[1] Univ Camerino, Sch Pharm, Pharmacol Unit, Via Madonna delle Carceri 9, I-62032 Camerino, MC, Italy

[2] Scripps Res Inst, Dept Neurosci, La Jolla, CA 92037 USA

[3] Ist Italian Tecnol, Ctr Neurosci & Cognit Syst UniTn, Corso Bettini 31, I-38068 Rovereto, Italy

[4] Univ Torino, Dept Mol Biotechnol & Hlth Sci, Turin, Italy

关键词: Alcoholism;    Ethanol;    Opioids;    Brain imaging;    CRF;    PET;    fMRI;   

DOI  :  10.1016/j.neubiorev.2019.05.014

来源: Elsevier

【 摘 要 】

Alcohol Use Disorder (AUD) is a chronic disease that develops over the years. The complexity of the neurobiological processes contributing to the emergence of AUD and the neuroadaptive changes occurring during disease progression make it difficult to improve treatments. On the other hand, this complexity offers researchers the possibility to explore new targets. Over years of intense research several molecules were tested in AUD; in most cases, despite promising preclinical data, the clinical efficacy appeared insufficient to justify futher development. A prototypical example is that of corticotropin releasing factor type 1 receptor (CRF1R) antagonists that showed significant effectiveness in animal models of AUD but were largely ineffective in humans. The present article attempts to analyze the most recent venues in the development of new medications in AUD with a focus on the most promising drug targets under current exploration. Moreover, we delineate the importance of using a more integrated translational framework approach to correlate preclinical findings and early clinical data to enhance the probability to validate biological targets of interest.

【 授权许可】

Free