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

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.

• Authors: Luise Haulund Vollesen, Song Guo, Malene Rohr Andersen, Messoud Ashina
• Journal: Cephalalgia : an international journal of headache (Cephalalgia) Vol. 39 Issue 5 Pg. 597-607 (04 2019) ISSN: 1468-2982 [Electronic] England
• PMID: 30165750 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• Histamine H1 Antagonists
• Pituitary Adenylate Cyclase-Activating Polypeptide
• Clemastine

Topics

• Adult
• Clemastine (therapeutic use)
• Cross-Over Studies
• Double-Blind Method
• Female
• Headache (chemically induced, prevention & control)
• Histamine H1 Antagonists (therapeutic use)
• Humans
• Male
• Middle Aged
• Migraine Disorders (chemically induced, prevention & control)
• Pituitary Adenylate Cyclase-Activating Polypeptide (adverse effects)
• Young Adult