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
Permalink -

https://acuresearchbank.acu.edu.au/item/8754x/structural-contributions-of-antipsychotic-drugs-to-their-therapeutic-profiles-and-metabolic-side-effects

Restricted files

Publisher's version

  • 114
    total views
  • 0
    total downloads
  • 4
    views this month
  • 0
    downloads this month
These values are for the period from 19th October 2020, when this repository was created.

Export as

Related outputs

Shifting towards a model of mGluR5 dysregulation in schizophrenia: Consequences for future schizophrenia treatment
Matosin, Natalie, Fernandez-Enright, Francesca, Lum, Jeremy S. and Newell, Kelly A.. (2017). Shifting towards a model of mGluR5 dysregulation in schizophrenia: Consequences for future schizophrenia treatment. Neuropharmacology. 115, pp. 73 - 91. https://doi.org/10.1016/j.neuropharm.2015.08.003
Molecular evidence of synaptic pathology in the CA1 region in schizophrenia
Matosin, Natalie, Fernandez-Enright, Francesca, Lum, Jeremy S., Engel, Martin, Andrews, Jessica L., Gassen, Nils C., Wagner, Klaus V., Schmidt, Mathias V. and Newell, Kelly A.. (2016). Molecular evidence of synaptic pathology in the CA1 region in schizophrenia. Schizophrenia. 2(16022), pp. 1 - 8. https://doi.org/10.1038/npjschz.2016.22
NMDA receptor antagonism by phencyclidine reduces NWASP and WAVE1 protein expression and reduces levels of myelination markers in the prefrontal cortex of rats
Andrews, Jessica L., Newell, Kelly A., Matosin, Natalie, Huang, Xu-Feng and Fernandez-Enright, Francesca Elizabeth. (2015). NMDA receptor antagonism by phencyclidine reduces NWASP and WAVE1 protein expression and reduces levels of myelination markers in the prefrontal cortex of rats. Journal of Pharmaceutics and Pharmacology. 3(1), pp. 1 - 8.
Alterations of mGluR5 and its endogenous regulators Norbin, Tamalin and Preso1 in schizophrenia: Towards a model of mGluR5 dysregulation
Matosin, Natalie, Fernandez-Enright, Francesca Elizabeth, Fung, Samantha Jane, Lum, Jeremy Stephen, Engel, Martin, Andrews, Jessica Lee, Huang, Xu-Feng, Weickert, Cynthia Shannon and Newell, Kelly Anne. (2015). Alterations of mGluR5 and its endogenous regulators Norbin, Tamalin and Preso1 in schizophrenia: Towards a model of mGluR5 dysregulation. Acta Neuropathologica. 130(1), pp. 119 - 129. https://doi.org/10.1007/s00401-015-1411-6
Alterations of p75 neurotrophin receptor and Myelin transcription factor 1 in the hippocampus of perinatal phencyclidine treated rats
Andrews, Jessica L., Newell, Kelly A., Matosin, Natalie, Huang, Xu-Feng and Fernandez-Enright, Francesca Elizabeth. (2015). Alterations of p75 neurotrophin receptor and Myelin transcription factor 1 in the hippocampus of perinatal phencyclidine treated rats. Progress in Neuropsychopharmacology and Biological Psychiatry. 56(63), pp. 91 - 97. https://doi.org/10.1016/j.pnpbp.2015.06.003
Genetic variants in Nogo receptor signaling pathways may be associated with early life adversity in schizophrenia susceptibility
Andrews, Jessica L. and Fernandez-Enright, Francesca Elizabeth. (2015). Genetic variants in Nogo receptor signaling pathways may be associated with early life adversity in schizophrenia susceptibility. Biochimica et Biophysica Acta Clinical. 3, pp. 36 - 43. https://doi.org/10.1016/j.bbacli.2014.11.008
Metabotropic glutamate receptor 5, and its trafficking molecules Norbin and Tamalin, are increased in the CA1 hippocampal region of subjects with schizophrenia
Matosin, Natalie, Fernandez-Enright, Francesca Elizabeth, Lum, Jeremy S., Andrews, Jessica L., Engel, Martin, Huang, Xu-Feng and Newell, Kelly A.. (2015). Metabotropic glutamate receptor 5, and its trafficking molecules Norbin and Tamalin, are increased in the CA1 hippocampal region of subjects with schizophrenia. Schizophrenia Research. 166(2017-03-01), pp. 212 - 218. https://doi.org/10.1016/j.schres.2015.05.001
Investigation of genetic variants in ubiquitin enzyme genes involved in the modulation of neurodevelopmental processes: A role in schizophrenia susceptibility?
Andrews, Jessica L. and Fernandez-Enright, Francesca. (2014). Investigation of genetic variants in ubiquitin enzyme genes involved in the modulation of neurodevelopmental processes: A role in schizophrenia susceptibility? Genetics Research. 96(e15), pp. 1 - 9. https://doi.org/10.1017/S0016672314000184
Metabotropic glutamate receptor mGluR2/3 and mGluR5 binding in the anterior cingulate cortex in psychotic and nonpsychotic depression, bipolar disorder and schizophrenia: Implications for novel mGluR-based therapeutics
Matosin, Natalie, Fernandez-Enright, Francesca, Frank, Elisabeth, Deng, Chao, Wong, Jenny, Huang, Xu-Feng and Newell, Kelly A.. (2014). Metabotropic glutamate receptor mGluR2/3 and mGluR5 binding in the anterior cingulate cortex in psychotic and nonpsychotic depression, bipolar disorder and schizophrenia: Implications for novel mGluR-based therapeutics. Journal of Psychiatry and Neuroscience. 39(6), pp. 407 - 416. https://doi.org/10.1503/jpn.130242
Novel implications of Lingo-1 and its signaling partners in schizophrenia
Fernandez-Enright, F., Andrews, J. L., Newell, K. A., Pantelis, C. and Huang, X.-F.. (2014). Novel implications of Lingo-1 and its signaling partners in schizophrenia. Translational Psychiatry. 4, pp. 1 - 8. https://doi.org/10.1038/tp.2013.121
In vivo pharmacological evaluations of novel olanzapine analogues in rats: A potential new avenue for the treatment of schizophrenia
Jafari, Somayeh, Huang, Xu-Feng, Andrews, Jessica L. and Fernandez-Enright, Francesca. (2013). In vivo pharmacological evaluations of novel olanzapine analogues in rats: A potential new avenue for the treatment of schizophrenia. PLoS ONE. 8(12), pp. 1 - 10. https://doi.org/10.1371/journal.pone.0080979
Novel olanzapine analogues presenting a reduced H 1 receptor affinity and retained 5HT 2A/D 2 binding affinity ratio
Jafari, Somayeh, Bouillon, Marc E., Huang, Xu-Feng, Pyne, Stephen G. and Fernandez-Enright, Francesca. (2012). Novel olanzapine analogues presenting a reduced H 1 receptor affinity and retained 5HT 2A/D 2 binding affinity ratio. BMC Pharmacology. 12(1), pp. 1 - 8. https://doi.org/10.1186/1471-2210-12-8