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A mass spectrometry imaging approach for investigating how drug-drug interactions influence drug blood-brain barrier permeability
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- Vallianatou, Theodosia (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab
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- Strittmatter, Nicole (author)
- AstraZeneca, IMED Biotech Unit, Pathol Sci Drug Safety & Metab, Cambridge, England
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- Nilsson, Anna (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab
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- (creator_code:org_t)
- Elsevier BV, 2018
- 2018
- English.
- In: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 172, s. 808-816
- Journal article (peer-reviewed)
Abstract
Subject headings
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- There is a high need to develop quantitative imaging methods capable of providing detailed brain localization information of several molecular species simultaneously. In addition, extensive information on the effect of the blood-brain barrier on the penetration, distribution and efficacy of neuroactive compounds is required. Thus, we have developed a mass spectrometry imaging method to visualize and quantify the brain distribution of drugs with varying blood-brain barrier permeability. With this approach, we were able to determine blood-brain barrier transport of different drugs and define the drug distribution in very small brain structures (e.g., choroid plexus) due to the high spatial resolution provided. Simultaneously, we investigated the effect of drug-drug interactions by inhibiting the membrane transporter multidrug resistance 1 protein. We propose that the described approach can serve as a valuable analytical tool during the development of neuroactive drugs, as it can provide physiologically relevant information often neglected by traditional imaging technologies.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Keyword
- Mass spectrometry imaging
- Blood-brain barrier
- Drug-drug interactions
- Elacridar
- Loperamide
- Propranolol
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- art (subject category)
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- Uppsala University
- Karolinska Institutet
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