Systemic neurotransmitter responses to clinically approved and experimental neuropsychiatric drugs

Hamid R. Noori (), Lewis H. Mervin, Vahid Bokharaie, Özlem Durmus, Lisamon Egenrieder, Stefan Fritze, Britta Gruhlke, Giulia Reinhardt, Hans-Hendrik Schabel, Sabine Staudenmaier, Nikos K. Logothetis, Andreas Bender and Rainer Spanagel
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Hamid R. Noori: University of Heidelberg
Lewis H. Mervin: University of Cambridge
Vahid Bokharaie: Max Planck Institute for Biological Cybernetics, Max Planck Ring 8
Özlem Durmus: University of Heidelberg
Lisamon Egenrieder: University of Heidelberg
Stefan Fritze: University of Heidelberg
Britta Gruhlke: University of Heidelberg
Giulia Reinhardt: University of Heidelberg
Hans-Hendrik Schabel: University of Heidelberg
Sabine Staudenmaier: University of Heidelberg
Nikos K. Logothetis: Max Planck Institute for Biological Cybernetics, Max Planck Ring 8
Andreas Bender: University of Cambridge
Rainer Spanagel: University of Heidelberg

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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–target 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–target interactions.

Date: 2018
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DOI: 10.1038/s41467-018-07239-1

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