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

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 H(1) receptors may significantly advance schizophrenia therapy.

• Authors: Somayeh Jafari, Francesca Fernandez-Enright, Xu-Feng Huang
• Journal: Journal of neurochemistry (J Neurochem) Vol. 120 Issue 3 Pg. 371-84 (Feb 2012) ISSN: 1471-4159 [Electronic] England
• PMID: 22103329 (Publication Type: Journal Article, Review)
• Copyright: © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

Chemical References

• Antipsychotic Agents
• Serotonin

Topics

• Animals
• Antipsychotic Agents (adverse effects, chemistry, pharmacology)
• Basal Ganglia Diseases (chemically induced)
• Humans
• Mental Disorders (drug therapy)
• Movement Disorders (etiology)
• Serotonin (metabolism)
• Structure-Activity Relationship
• Weight Gain (drug effects)