Tadalafil Associated with Typical Migraine Aura without Headache

Dinn, R.; Wall, Michael

doi:10.1111/j.1468-2982.2006.01188.x

Cited by 11 publications

(4 citation statements)

References 16 publications

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“…The headache-eliciting effects of PDEs have not been tested in MA patients. In a case report, tadalafil was associated with visual aura symptoms (75).…”

Section: Phosphodiesterase (Pde) Inhibitor Modelmentioning

confidence: 99%

Pearls and pitfalls in human pharmacological models of migraine: 30 years' experience

2013

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In vitro studies have contributed to the characterization of receptors in cranial blood vessels and the identification of new possible anti-migraine agents. In vivo animal models enable the study of vascular responses, neurogenic inflammation, peptide release and genetic predisposition and thus have provided leads in the search for migraine mechanisms. All animal-based results must, however, be validated in human studies because so far no animal models can predict the efficacy of new therapies for migraine. Given the nature of migraine attacks, fully reversible and treatable, the headache- or migraine-provoking property of naturally occurring signaling molecules can be tested in a human model. If such an endogenous substance can provoke migraine in human patients, then it is likely, although not certain, that blocking its effect will be effective in the treatment of acute migraine attacks. To this end, a human in vivo model of experimental headache and migraine in humans has been developed. Human models of migraine offer unique possibilities to study mechanisms responsible for migraine and to explore the mechanisms of action of existing and future anti-migraine drugs. The human model has played an important role in translational migraine research leading to the identification of three new principally different targets in the treatment of acute migraine attacks and has been used to examine other endogenous signaling molecules as well as genetic susceptibility factors. New additions to the model, such as advanced neuroimaging, may lead to a better understanding of the complex events that constitute a migraine attack, and better and more targeted ways of intervention.

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“…The headache-eliciting effects of PDEs have not been tested in MA patients. In a case report, tadalafil was associated with visual aura symptoms (75).…”

Section: Phosphodiesterase (Pde) Inhibitor Modelmentioning

confidence: 99%

Pearls and pitfalls in human pharmacological models of migraine: 30 years' experience

2013

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“…Sildenafil, an inhibitor of cGMP-degrading phosphodiesterase 5 (PDE5), used for pulmonary arterial hypertension and erectile dysfunction, induces headache in healthy individuals and migraine-like headache in patients with migraine without aura (1,12). Interestingly, in a case report, the selective PDE5-inhibitor, tadalafil, consistently induced typical visual aura without headache 72 hours after administration in a patient with no history of migraine or significant visual disturbances (13). It is of great interest to investigate if cGMP accumulation can induce migraine-like headache, and, more importantly, migraine aura in patients with migraine with aura (MA) to disclose a possible common pathway of the aura and migraine headache initiation and to determine if such a pathway involves the signaling molecules known to be important in the induction of migraine-like headache.…”

Section: Introductionmentioning

confidence: 99%

The headache and aura-inducing effects of sildenafil in patients with migraine with aura

2022

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Introduction It has not been established if migraine headache and migraine aura share common pathophysiological mechanisms. Sildenafil, a phosphodiesterase-5 inhibitor, causes cGMP accumulation and provokes migraine-like headache in patients with migraine without aura. We investigated if sildenafil induced aura and migraine-like headache in patients with migraine with aura. Methods In a randomized, double-blinded, placebo-controlled crossover study, 16 patients with migraine with aura (of whom 11 patients exclusively had attacks of migraine with aura) received 100 mg sildenafil or placebo on two separate days. The development, duration, and characteristics of aura and headache were recorded using a questionnaire. The primary outcome was the incidence of migraine aura. Results Aura symptoms were induced in three patients (19%) after sildenafil and none after placebo (P < 0.001). After administration of sildenafil, 12 patients (75%) developed headache compared with two patients (12.5%) after placebo (Fisher’s exact test, P < 0.001). The headache in nine patients (56%) after sildenafil and one patient (6%) after placebo fulfilled the criteria for migraine-like attacks (Fisher’s exact test, P = 0.002). All patients, who fulfilled the criteria for migraine-like attacks, reported that the attack mimicked the headache phase during their usual migraine attacks. Discussion Sildenafil have a moderate migraine headache-inducing and a modest aura-inducing effect in patients with migraine with aura, even in those who exclusively experienced attacks of migraine with aura in their spontaneous attacks. These findings suggest that accumulation of cGMP by PDE5-inhibition do not play any significant role in the initiation of migraine aura and refute the hypothesis of sildenafil being a tool for pharmacological provocation of this phenomenon. These findings further support dissociation between the aura and the headache phase. Trial registration: ClinicalTrials.gov – NCT02795351

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“…Two studies reported aura after the consumption of two different food sources (50,51). Hypoxia (52) and 11 different pharmaceutical drugs were reported to precipitate aura in one patient each (50,52–62). One article reported aura after GTN infusion (63) and one following the transdermal application of GTN (64).…”

Section: Resultsmentioning

confidence: 99%

Can migraine aura be provoked experimentally? A systematic review of potential methods for the provocation of migraine aura

et al. 2016

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Background The nature of the migraine aura and its role in migraine pathophysiology is incompletely understood. In particular, the mechanisms underlying aura initiation and the causal relation between aura and headache are unknown. The scientific investigation of aura in patients is only possible if aura can be triggered. This paper reviews potential methods for the experimental provocation of migraine aura. Methods We systematically searched PubMed for studies of experimental migraine provocation, including case reports of patients with aura and reports of the occurrence of aura following exposure to any kind of suspected trigger. Results We identified 21 provocation studies, using 13 different prospective provocation methods, and 34 case reports. In the prospective studies, aura were reported following the administration of intravenous and sublingual glyceryl trinitrate, visual stimulation, physical activity, calcitonin gene-related peptide infusion, chocolate ingestion, and the intravenous injection of insulin. In addition, carotid artery puncture has consistently been reported as a trigger of aura. Conclusions No safe and efficient method for aura provocation exists at present, but several approaches could prove useful for this purpose.

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Tadalafil Associated with Typical Migraine Aura without Headache

Cited by 11 publications

References 16 publications

Pearls and pitfalls in human pharmacological models of migraine: 30 years' experience

Pearls and pitfalls in human pharmacological models of migraine: 30 years' experience

The headache and aura-inducing effects of sildenafil in patients with migraine with aura

Can migraine aura be provoked experimentally? A systematic review of potential methods for the provocation of migraine aura

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