title: Ictal lack of binding to brain parenchyma suggests integrity of the blood-brain barrier for 11C-dihydroergotamine during glyceryl trinitrate-induced migraine.
abstract: SEE DREIER DOI 101093/AWW112 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: For many decades a breakdown of the blood-brain barrier has been postulated to occur in migraine. Hypothetically this would facilitate access of medications, such as dihydroergotamine or triptans, to the brain despite physical properties otherwise restricting their entry. We studied the permeability of the blood-brain barrier in six migraineurs and six control subjects at rest and during acute glyceryl trinitrate-induced migraine attacks using positron emission tomography with the novel radioligand (11)C-dihydroergotamine, which is chemically identical to pharmacologically active dihydroergotamine. The influx rate constant Ki, average dynamic image and time activity curve were assessed using arterial blood sampling and served as measures for receptor binding and thus blood-brain barrier penetration. At rest, there was binding of (11)C-dihydroergotamine in the choroid plexus, pituitary gland, and venous sinuses as expected from the pharmacology of dihydroergotamine. However, there was no binding to the brain parenchyma, including the hippocampus, the area with the highest density of the highest-affinity dihydroergotamine receptors, and the raphe nuclei, a postulated brainstem site of action during migraine, suggesting that dihydroergotamine is not able to cross the blood-brain barrier. This binding pattern was identical in migraineurs during glyceryl trinitrate-induced migraine attacks as well as in matched control subjects. We conclude that (11)C-dihydroergotamine is unable to cross the blood-brain barrier interictally or ictally demonstrating that the blood-brain barrier remains tight for dihydroergotamine during acute glyceryl trinitrate-induced migraine attacks.
authors.affiliation: 1 Headache Group, Department of Neurology, University of California San Francisco, San Francisco, CA, USA 3 Department of Neurology, University Hospital Bern - Inselspital, University of Bern, Bern, Switzerland 4 Headache Group, NIHR-Wellcome Trust, King's Clinical Research Facility, King's College London, London, UK.
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Schankin
authors.affiliation: 1 Headache Group, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Farooq H
authors.initials: FH
authors.lastname: Maniyar
authors.affiliation: 2 Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Youngho
authors.initials: Y
authors.lastname: Seo
authors.affiliation: 5 MAP Pharmaceuticals, Inc., Mountain View, CA, USA.
authors.forename: Shashidar
authors.initials: S
authors.lastname: Kori
authors.affiliation: 1 Headache Group, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Eller
authors.affiliation: 6 Department of Neurology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Denise E
authors.initials: DE
authors.lastname: Chou
authors.affiliation: 2 Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Blecha
authors.affiliation: 2 Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Stephanie T
authors.initials: ST
authors.lastname: Murphy
authors.affiliation: 2 Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Randall A
authors.initials: RA
authors.lastname: Hawkins
authors.affiliation: 7 Department of Neurology, DKD Helios Klinik, Wiesbaden, Germany.
authors.forename: Till
authors.initials: T
authors.lastname: Sprenger
authors.affiliation: 2 Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Henry F
authors.initials: HF
authors.lastname: VanBrocklin
authors.affiliation: 1 Headache Group, Department of Neurology, University of California San Francisco, San Francisco, CA, USA 4 Headache Group, NIHR-Wellcome Trust, King's Clinical Research Facility, King's College London, London, UK peter.goadsby@kcl.ac.uk.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Goadsby
mesh_terms: D000328:Adult; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging / Q000378:metabolism; D004087:Dihydroergotamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000000981:diagnostic imaging / Q000378:metabolism; D005996:Nitroglycerin / Q000494:pharmacology*; D049268:Positron-Emission Tomography / Q000379:methods*; D014662:Vasoconstrictor Agents / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D004087:Dihydroergotamine; D005996:Nitroglycerin
keywords: drug treatment; headache; imaging; migraine