Structural contributions of antipsychotic drugs to their therapeutic profiles and metabolic side effects

Journal article


Jafari, Somayeh, Fernandez-Enright, Francesca and Huang, Xu-Feng. (2012). Structural contributions of antipsychotic drugs to their therapeutic profiles and metabolic side effects. Journal of Neurochemistry. 120(3), pp. 371 - 384. https://doi.org/10.1111/j.1471-4159.2011.07590.x
AuthorsJafari, Somayeh, Fernandez-Enright, Francesca and Huang, Xu-Feng
Abstract

Antipsychotic drugs have various neuropharmacological properties as a result of their structural diversity. Despite their therapeutic benefits, most of the prescribed atypical antipsychotics can induce severe side effects, including weight gain, type II diabetes mellitus, and cardiovascular diseases. Among the developed atypical antipsychotic agents, tetracyclic dibenzodiazepine and thienobenzodiazepine compounds, particularly clozapine and olanzapine, are associated with the greatest weight gain and metabolic disturbances. However, the unique chemical structure of these compounds causes the low risk of side effects reported for typical antipsychotics (e.g. extrapyramidal symptoms and tardive dyskinesia). This report reviews the recent discovery of the potential role of the chemical structure of antipsychotics in their therapeutic properties and metabolic disturbances. By developing structure–activity relationship studies for atypical antipsychotics, we will improve our understanding of the structural modifications of these chemical classes that lead to reduced weight gain, which will be an invaluable step toward the discovery of the next generation of atypical antipsychotics. In this review, we suggest that a novel dibenzodiazepine or thienobenzodiazepine antipsychotic drug with lower affinity for H1 receptors may significantly advance schizophrenia therapy.

Keywordsantipsychotics; dibenzodiazepines; metabolic side effect; SAR; structural modification; thienobenzodiazepines
Year2012
JournalJournal of Neurochemistry
Journal citation120 (3), pp. 371 - 384
PublisherBlackwell Publishing Inc.
ISSN0022-3042
Digital Object Identifier (DOI)https://doi.org/10.1111/j.1471-4159.2011.07590.x
Scopus EID2-s2.0-84855701701
Page range371 - 384
Research GroupSchool of Behavioural and Health Sciences
Publisher's version
File Access Level
Controlled
Place of publicationUnited Kingdom
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