title: Phosphodiesterase 3 inhibitor cilostazol induces migraine-like attacks via cyclic AMP increase.
abstract: The initiating mechanisms of migraine attacks are very complex but may involve the cyclic AMP signalling pathway. It is unknown whether intracellular cyclic AMP accumulation induces migraine attacks. We investigated whether administration of cilostazol, which causes cyclic AMP accumulation, may induce migraine attacks. We included 14 migraine patients without aura in a double-blind, placebo-controlled crossover study. All participants received oral cilostazol or placebo on two separate days. We recorded migraine headache characteristics, associated symptoms and time of rescue medication intake using a questionnaire. Cilostazol induced delayed migraine-like attacks in 12 patients (86%) compared with two (14%) patients after placebo (P = 0.002). The median time to onset for migraine-like attacks was 6 h (range 3-11 h). Patients reported that the attacks mimicked their usual migraine attacks and that cilostazol-induced attacks responded to their usual migraine treatment. Median time of medication intake was 6 h (range 4-11 h). The present study suggests that intracellular cyclic AMP accumulation plays a crucial role in migraine induction. This knowledge is a further step in our understanding of the intracellular pathway of migraine initiation.
authors.affiliation: Danish Headache Centre and Department of Neurology, Glostrup Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2600 Glostrup, Copenhagen, Denmark.
authors.forename: Song
authors.initials: S
authors.lastname: Guo
authors.affiliation: Danish Headache Centre and Department of Neurology, Glostrup Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2600 Glostrup, Copenhagen, Denmark.
authors.forename: Jes
authors.initials: J
authors.lastname: Olesen
authors.affiliation: Danish Headache Centre and Department of Neurology, Glostrup Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2600 Glostrup, Copenhagen, Denmark ashina@dadlnet.dk.
authors.forename: Messoud
authors.initials: M
authors.lastname: Ashina
mesh_terms: D000328:Adult; D000077407:Cilostazol; D018592:Cross-Over Studies; D000242:Cyclic AMP / Q000378:metabolism*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020326:Migraine without Aura / Q000139:chemically induced* / Q000503:physiopathology; D058987:Phosphodiesterase 3 Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D010919:Placebos; D013777:Tetrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D013997:Time Factors; D055815:Young Adult
chemical_list: D058987:Phosphodiesterase 3 Inhibitors; D010919:Placebos; D013777:Tetrazoles; D000242:Cyclic AMP; D000077407:Cilostazol
keywords: cilostazol; cyclic adenosine monophosphate; headache; migraine; phosphodiesterase inhibitor