Article 2018

Systemic neurotransmitter responses to clinically approved and experimental neuropsychiatric drugs

{Neuropsychiatric disorders are the third leading cause of global disease burden. Current pharmacological treatment for these disorders is inadequate, with often insufficient efficacy and undesirable side effects. One reason for this is that the links between molecular drug action and neurobehavioral drug effects are elusive. We use a big data approach from the neurotransmitter response patterns of 258 different neuropsychiatric drugs in rats to address this question. Data from experiments comprising 110,674 rats are presented in the Syphad database [www.syphad.org]. Chemoinformatics analyses of the neurotransmitter responses suggest a mismatch between the current classification of neuropsychiatric drugs and spatiotemporal neurostransmitter response patterns at the systems level. In contrast, predicted drug\textendashtarget interactions reflect more appropriately brain region related neurotransmitter response. In conclusion the neurobiological mechanism of neuropsychiatric drugs are not well reflected by their current classification or their chemical similarity, but can be better captured by molecular drug\textendashtarget interactions.}

Author(s): Noori, HR and Mervin, LH and Bokharaie, V and Durmus, Ö and Egenrieder, L and Fritze, S and Gruhlke, B and Reinhardt, G and Schabel, H-H and Staudenmaier, S and Logothetis, NK and Bender, A and Spanagel, R
Journal: {Nature Communications}
Volume: 9
Pages: 1--14
Year: 2018
Publisher: Nature Publishing Group
Bibtex Type: Article (article)
DOI: 10.1038/s41467-018-07239-1
Address: London
Electronic Archiving: grant_archive

BibTex

@article{item_3007977,
  title = {{Systemic neurotransmitter responses to clinically approved and experimental neuropsychiatric drugs}},
  journal = {{Nature Communications}},
  abstract = {{Neuropsychiatric disorders are the third leading cause of global disease burden. Current pharmacological treatment for these disorders is inadequate, with often insufficient efficacy and undesirable side effects. One reason for this is that the links between molecular drug action and neurobehavioral drug effects are elusive. We use a big data approach from the neurotransmitter response patterns of 258 different neuropsychiatric drugs in rats to address this question. Data from experiments comprising 110,674 rats are presented in the Syphad database [www.syphad.org]. Chemoinformatics analyses of the neurotransmitter responses suggest a mismatch between the current classification of neuropsychiatric drugs and spatiotemporal neurostransmitter response patterns at the systems level. In contrast, predicted drug\textendashtarget interactions reflect more appropriately brain region related neurotransmitter response. In conclusion the neurobiological mechanism of neuropsychiatric drugs are not well reflected by their current classification or their chemical similarity, but can be better captured by molecular drug\textendashtarget interactions.}},
  volume = {9},
  pages = {1--14},
  publisher = {Nature Publishing Group},
  address = {London},
  year = {2018},
  slug = {item_3007977},
  author = {Noori, HR and Mervin, LH and Bokharaie, V and Durmus, \"O and Egenrieder, L and Fritze, S and Gruhlke, B and Reinhardt, G and Schabel, H-H and Staudenmaier, S and Logothetis, NK and Bender, A and Spanagel, R}
}