Novel olanzapine analogues presenting a reduced H 1 receptor affinity and retained 5HT 2A/D 2 binding affinity ratio

Journal article

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
AuthorsJafari, Somayeh, Bouillon, Marc E., Huang, Xu-Feng, Pyne, Stephen G. and Fernandez-Enright, Francesca
Abstract

Background: Olanzapine is an atypical antipsychotic drug with high clinical efficacy, but which can cause severe weight gain and metabolic disorders in treated patients. Blockade of the histamine 1 (H1) receptors is believed to play a crucial role in olanzapine induced weight gain, whereas the therapeutic effects of this drug are mainly attributed to its favourable serotoninergic 2A and dopamine 2 (5HT2A/D2) receptor binding affinity ratios. Results: We have synthesized novel olanzapine analogues 8a and 8b together with the already known derivative 8c and we have examined their respective in vitro affinities for the 5HT2A, D2, and H1 receptors. Conclusions: We suggest that thienobenzodiazepines 8b and 8c with lower binding affinity for the H1 receptors, but similar 5HT2A/D2 receptor binding affinity ratios to those of olanzapine. These compounds may offer a better pharmacological profile than olanzapine for treating patients with schizophrenia.

Keywordsolanzapine; novel antipsychotics; 5HT2A/D2 affinity ratio; H1 receptors
Year2012
JournalBMC Pharmacology
Journal citation12 (1), pp. 1 - 8
PublisherBioMed Central
ISSN1471-2210
Digital Object Identifier (DOI)https://doi.org/10.1186/1471-2210-12-8
Scopus EID2-s2.0-84862564982
Open accessOpen access
Page range1 - 8
Research GroupSchool of Behavioural and Health Sciences
Publisher's version
License
Place of publicationUnited Kingdom
Permalink -

https://acuresearchbank.acu.edu.au/item/8v068/novel-olanzapine-analogues-presenting-a-reduced-h-1-receptor-affinity-and-retained-5ht-2a-d-2-binding-affinity-ratio

Log in to edit

Download files

Publisher's version
OA_Jafari_2012_Novel_olanzapine_analogues_presenting_a_reduced.pdf
License: CC BY 3.0

  • 59
    total views
  • 70
    total downloads
  • 1
    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
Structural contributions of antipsychotic drugs to their therapeutic profiles and metabolic side effects
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