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Novel olanzapine analogues presenting a reduced H1 receptor affinity and retained 5HT2A/D2 binding affinity ratio

Journal Article


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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.

Publication Date


  • 2012

Citation


  • Jafari, S., Bouillon, M. E., Huang, X., Pyne, S. G. & Fernandez-Enright, F. (2012). Novel olanzapine analogues presenting a reduced H1 receptor affinity and retained 5HT2A/D2 binding affinity ratio. BMC Pharmacology, 12 (June), 1-8.

Scopus Eid


  • 2-s2.0-84862564982

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1337&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/325

Has Global Citation Frequency


Number Of Pages


  • 7

Start Page


  • 1

End Page


  • 8

Volume


  • 12

Issue


  • June

Place Of Publication


  • United Kingdom

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.

Publication Date


  • 2012

Citation


  • Jafari, S., Bouillon, M. E., Huang, X., Pyne, S. G. & Fernandez-Enright, F. (2012). Novel olanzapine analogues presenting a reduced H1 receptor affinity and retained 5HT2A/D2 binding affinity ratio. BMC Pharmacology, 12 (June), 1-8.

Scopus Eid


  • 2-s2.0-84862564982

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1337&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/325

Has Global Citation Frequency


Number Of Pages


  • 7

Start Page


  • 1

End Page


  • 8

Volume


  • 12

Issue


  • June

Place Of Publication


  • United Kingdom