Analyzing the Effects of Psychotropic Drugs on Metabolite Profiles in Rat Brain Using1H NMR Spectroscopy
Abstract
The mechanism of action of standard drug treatments for psychiatric disorders remains fundamentally unknown, despite intensive investigation in academia and the pharmaceutical industry. So far, little is known about the effects of psychotropic medications on brain metabolism in either humans or animals. In this study, we investigated the effects of a range of psychotropic drugs on rat brain metabolites. The drugs investigated were haloperidol, clozapine, olanzapine, risperidone, aripiprazole (antipsychotics); valproate, carbamazapine (mood stabilizers) and phenytoin (antiepileptic drug). The relative concentrations of endogenous metabolites were determined using high-resolution proton nuclear magnetic resonance (1H NMR) spectroscopy. The results revealed that different classes of psychotropic drugs modulated a range of metabolites, where each drug induced a distinct neurometabolic profile. Some common responses across several drugs or within a class of drug were also observed. Antipsychotic drugs and mood stabilizers, with the exception of olanzapine, consistently increased N-acetylaspartate (NAA) levels in at least one brain area, suggesting a common therapeutic response on increased neuronal viability. Most drugs also altered the levels of several metabolites associated with glucose metabolism, neurotransmission (including glutamate and aspartate) and inositols. The heterogenic pharmacological response reflects the functional and physiological diversity of the therapeutic interventions, including side effects. Further study of these metabolites in preclinical models should facilitate the development of novel drug treatments for psychiatric disorders with improved efficacy and side effect profiles.
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The effects of antipsychotic medication cannot be discounted because it has been suggested that haloperidol, clozapine, and olanzapine cause reductions in glutamatergic levels in the rat brain.
“The effects of antipsychotic medication cannot be discounted because it has been suggested that haloperidol, clozapine, and olanzapine cause reductions in glutamatergic levels in the rat brain.58”
From Glutamate in Schizophrenia: A Focused Review and Meta-Analysis of 1H-MRS Studies (2013) · cites this paper as [58]
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- Authors
- McLoughlin, G. A., Ma, D., Tsang, T. M., Jones, D. N. C., Cilia, J., Hill, M. D., Robbins, M. J., Benzel, I. M., Maycox, P. R., Holmes, E., & Bahn, S.
- Affiliations
- Department of Biomolecular Medicine, Division of SORA, Faculty of Medicine, Imperial College, London, SW7 2AZ, U.K., Institute of Biotechnology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QT, U.K., and Psychiatry CEDD, New Frontiers Science Park, GlaxoSmithKline, Third Avenue, Harlow, CM19 5AW, U.K.
- GlaxoSmithKline (United Kingdom) (GB)
- Corresponding author
- Bahn, Sabine
- Venue
- Journal of Proteome Research
- Publisher
- American Chemical Society (ACS)
- Published
- 2009-03-11
- Volume
- 8
- Issue
- 4
- Pages
- 1943-1952
- ISSN
- 1535-3893 (ISSN-L)
- 1535-3907
- OpenAlex
- W2088807992
- Cited by
- 63
- References
- 78
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 3 · 2022: 7 · 2021: 2 · 2020: 8 · 2019: 3 · 2018: 1 · 2017: 3 · 2016: 2 · 2015: 4 · 2014: 4 · 2012: 9
- FWCI
- 3.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Proteome Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- psychotropic drugs, brain metabolites, antipsychotic drugs, mood stabilizers, antiepileptic drugs, N-acetylaspartate, neuronal viability, glucose metabolism, glutamate, aspartic acid, myo-inositol, mental illness, adverse drug reactions, rat brain
- MeSH terms
- Animals, Brain, Magnetic Resonance Spectroscopy, Oligodendroglia, Psychotropic Drugs, Rats
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