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Cephalalgia. 2019 Apr;39(5):597-607. doi: 10.1177/0333102418798611. Epub 2018 Aug 30.

Effect of the H1-antihistamine clemastine on PACAP38 induced migraine.

Author information

1
1 Danish Headache Centre and Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
2
2 Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Hellerup, Denmark.

Abstract

OBJECTIVE:

To investigate the effect of the H1-antihistamine clemastine on the migraine-inducing abilities of pituitary adenylate cyclase activating peptide-38.

METHODS:

We conducted a double-blind, randomized, placebo controlled two-way cross-over study. Twenty migraine without aura patients were randomly allocated to receive bolus clemastine 2 mg (1 mg/ml) or bolus saline 2 ml intravenously over 2 min on two study days. Following each bolus injection, 10 pmol/kg/min of pituitary adenylate cyclase activating peptide-38 was administered intravenously over 20 min. We recorded migraine/headache characteristics every 10 min until 90 min after the start of infusion, and collected blood to investigate mast cell degranulation and the inflammation markers tryptase and tumor necrosis factor-alpha before and after infusion of pituitary adenylate cyclase activating peptide-38.

RESULTS:

After clemastine pretreatment, five out of 20 participants developed a migraine-like attack in response to a pituitary adenylate cyclase activating peptide-38 infusion compared to nine out of 20 after placebo pretreatment ( p = 0.288). Following clemastine pretreatment, 15 out of 20 participants reported headache in response to a pituitary adenylate cyclase activating peptide-38 infusion, whereas 19 out of 20 participants did so following placebo pretreatment ( p = 0.221). We found no difference in area under the curve 12 h for headache intensity between the two experimental days ( p = 0.481). We found no difference in area under the curve 180 min for tryptase ( p = 0.525) or tumor necrosis factor-alpha ( p = 0.487) between clemastine and placebo pretreatment days.

CONCLUSION:

H1-antihistamine, clemastine, failed to prevent migraine or headache after pituitary adenylate cyclase activating peptide-38 infusion, thus making a role for histamine release or mast cell degranulation in pituitary adenylate cyclase activating peptide-38-induced migraine less likely.

KEYWORDS:

PAC receptor; PACAP38; antihistamine; mast cells; migraine

PMID:
30165750
DOI:
10.1177/0333102418798611

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