Distribution of haloperidol, risperidone, raclopride and flumazenil in cortex, corpus callosum and striatum
Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
Introduction The treatment of psychotic disorders uses antipsychotic drugs, acting by blocking dopamine in the brain’s cortex. Most patients experience extrapyramidal side effects because of dopamine blockage in the motor center in the striatum. Antipsychotics show varying degrees of these side effects. Defining the distribution (Vu,brain) of the drug could determine the specific binding, which could explain the differences. Haloperidol and risperidone and the PET-ligands raclopride and flumazenil were chosen to investigate in this study. PET-ligands used when performing a PET-scan, show the distribution of a certain receptor in different brain regions. Aim The aim of the project was to evaluate the Vu,brain of haloperidol, risperidone, raclopride and flumazenil in different regions of the brain: cortex, corpus callosum and striatum using the brain slice method, in order to understand if there may be differences in the binding of these drugs in the brain regions. Materials and Method The brain slice method was used. Six slices from a rat brain was cut and put into a buffer containing the drug being investigated. After 5 h incubation a buffer sample was taken. Four slices were dissected and the amount of drug in each region was determined using liquid chromatography tandem mass spectrometry and compared to the amount in an entire brain slice. Results Vu,brain of risperidone in the entire brain slice was 15.3 mL g brain-1. Kp,uu,cell was 0,76, showing predominant extracellular distribution of risperidone. Discussion The aim was not met due to analytical difficulties, but as the questions formulated in this project are still very relevant, further research is needed. Results could possibly have a large bearing for the practicing clinician, as well as drug developing companies.
Place, publisher, year, edition, pages
2014. , 21 p.
IdentifiersURN: urn:nbn:se:uu:diva-237431OAI: oai:DiVA.org:uu-237431DiVA: diva2:767937
Subject / course
Bachelor of Science Programme in Pharmacy