Thomas Kaulisch1, Holger Rosenbrock2,
Detlef Stiller3
1In-Vivo Imaging, Target
Discovery Research , Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach,
Germany; 2CNS Diseases Research, Boehringer Ingelheim Pharma GmbH
& Co. KG, Biberach, Germany; 3In-Vivo Imaging, Target
Discovery Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach,
Germany
Acetylcholinesterase inhibitors (AChEI) are used for the treatment of mild cognitive impairment (MCI) symptoms in Alzheimers disease. Pharmacological MRI (phMRI) can be used to study the dose-response relationship of a pharmacological challenge in the brain. The AChEI donepizil was studied with an rCBV-based MR read-out in rats at two doses (0.2 and 0.5 mg/kg) and compared to challenge with nicotine or the carboanhydrase inhibitor acetazolamid (ACZ); the latter testing the cerebral vascular reserve. A clear dose-response relation was observed being most pronounced in cortical regions. High dose of donepezil yielded changes in rCBV nearly reaching the vascular reserve.