Evaluation of Drug Exposure and Metabolism in Locust and Zebrafish Brains Using Mass Spectrometry Imaging

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Standard

Harvard

APA

CBE

MLA

Vancouver

Author

RIS

TY - JOUR

T1 - Evaluation of Drug Exposure and Metabolism in Locust and Zebrafish Brains Using Mass Spectrometry Imaging

AU - Villacrez, Marvin

AU - Hellman, Karin

AU - Ono, Tatsuya

AU - Sugihara, Yutaka

AU - Rezeli, Melinda

AU - Ek, Fredrik

AU - Marko-Varga, Gyorgy

AU - Olsson, Roger

PY - 2018/8/15

Y1 - 2018/8/15

N2 - Studying how and where drugs are metabolized in the brain is challenging. In an entire organism, peripheral metabolism produces many of the same metabolites as those in the brain, and many of these metabolites can cross the blood-brain barrier from the periphery, thus making the relative contributions of hepatic and brain metabolism difficult to study in vivo. In addition, drugs and metabolites contained in ventricles and in the residual blood of capillaries in the brain may overestimate drugs' and metabolites' concentrations in the brain. In this study, we examine locusts and zebrafish using matrix assisted laser desorption ionization mass spectrometry imaging to study brain metabolism and distribution. These animal models are cost-effective and ethically sound for initial drug development studies.

AB - Studying how and where drugs are metabolized in the brain is challenging. In an entire organism, peripheral metabolism produces many of the same metabolites as those in the brain, and many of these metabolites can cross the blood-brain barrier from the periphery, thus making the relative contributions of hepatic and brain metabolism difficult to study in vivo. In addition, drugs and metabolites contained in ventricles and in the residual blood of capillaries in the brain may overestimate drugs' and metabolites' concentrations in the brain. In this study, we examine locusts and zebrafish using matrix assisted laser desorption ionization mass spectrometry imaging to study brain metabolism and distribution. These animal models are cost-effective and ethically sound for initial drug development studies.

KW - blood-brain barrier

KW - clozapine

KW - drug metabolism

KW - Locust

KW - Mass spectrometry imaging

KW - zebrafish

U2 - 10.1021/acschemneuro.7b00459

DO - 10.1021/acschemneuro.7b00459

M3 - Article

VL - 9

SP - 1994

EP - 2000

JO - ACS Chemical Neuroscience

T2 - ACS Chemical Neuroscience

JF - ACS Chemical Neuroscience

SN - 1948-7193

IS - 8

ER -