Levodopa pharmacokinetics -from stomach to brain : A study on patients with Parkinson’s disease

............................................................................................................................. 1 SVENSK SAMMANFATTNING ......................................................................................... 2 LIST OF PAPERS.................................................................................................................... 3 ABBREVIATIONS ................................................................................................................. 4 INTRODUCTION.................................................................................................................... 6 Parkinson’s Disease .......................................................................................................... 6 The Basal Ganglia............................................................................................................. 7 Treatment of Parkinson’s Disease ................................................................................10 Levodopa ...................................................................................................................10 Levodopa in the periphery .............................................................................11 Levodopa in the brain ....................................................................................13 Motor Complications .....................................................................................14 MAO-inhibitors ........................................................................................................16 Dopamine Agonists ..................................................................................................17 Deep Brain Stimulation ...........................................................................................17 Gastric Emptying ............................................................................................................19 AIMS OF THE THESIS........................................................................................................20 METHODS .............................................................................................................................21 Microdialysis ...................................................................................................................21 Carbon-labeled Octanoic Acid Breath Test .................................................................28 Lumbar Puncture .............................................................................................................28 Mass Spectrometry .........................................................................................................28 High-performance Liquid Chromatography................................................................29 Deep Brain Stimulation..................................................................................................30 Statistics ...........................................................................................................................32 PATIENTS AND MATERIALS..........................................................................................33 Patient selection ..............................................................................................................33 Materials and Chemicals ................................................................................................34 REVIEW OF THE PAPERS AND MAIN RESULTS .....................................................36 DISCUSSION .........................................................................................................................47