Amplifying Effect of Sumatriptan on Noradrenaline Venoconstriction in Migraine Patients

Panconesi, Alessandro; Franchi, G; Anselmi, B; Curradi, C; Tarquini, B

doi:10.1046/j.1468-2982.1993.1306383.x

Cited by 5 publications

(4 citation statements)

References 28 publications

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“…Collectively, these findings are in keeping with recent evidence that sumatriptan displaces a radiotracer binding to brain 5HT1 B receptors (15), and corroborate prior work indicating the ability of sumatriptan to cross the BBB (see (13) for a comprehensive review). Data are also in line with the ability of subcutaneous sumatriptan to prompt quick migraine/CH relief, as well as central side effects soon after the injection (14,21). Clinical evidence demonstrates that functional disability improves in CH patients as soon as 0.5–5 min after subdermal administration (18–20).…”

Section: Discussionsupporting

confidence: 65%

“…Such an ultra-rapid effect suggests the ability of parenteral sumatriptan to readily reach the site of pain origin and/or the CH generator. In this regard, evidence that nausea occurs within 2-5 minutes after sumatriptan injection (21) indicate that the drug rapidly reaches the brain parenchyma. To our knowledge, however, there are no data on the ability of sumatriptan to enter the brain within this very short time frame.…”

Section: Introductionmentioning

confidence: 99%

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Ultra-rapid brain uptake of subcutaneous sumatriptan in the rat: Implication for cluster headache treatment

et al. 2019

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Background In spite of the substantial therapeutic efficacy of triptans, their site of action is still debated. Subcutaneous sumatriptan is the most efficacious symptomatic treatment for cluster headache (CH) patients, showing therapeutic onset within a few minutes after injection even in migraine patients. However, whether subcutaneous sumatriptan is able to reach the CNS within this short time frame is currently unknown. Methods Here, by means of liquid chromatography/mass spectrometry, we investigated peripheral and brain distribution of subcutaneous sumatriptan soon after injection in rats at a dose equivalent to that used in patients. Tissue sumatriptan contents were compared to those of oxazepam, a prototypical lipophilic, neuroactive drug. Results We report that sumatriptan accumulated within brain regions of relevance to migraine and CH pathogenesis such as the hypothalamus and the brainstem as soon as 1 and 5 minutes after injection. Notably, sumatriptan brain distribution was faster than that of oxazepam, reaching concentrations exceeding its reported binding affinity for 5HT1B/D receptors, and in the range of those able to inhibit neurotransmitter release in vivo. Conclusion Our findings indicate that sumatriptan distributes within the CNS soon after injection, and are in line with prompt pain relief by parenteral sumatriptan in CH patients.

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Section: Discussionsupporting

confidence: 65%

Section: Introductionmentioning

confidence: 99%

Ultra-rapid brain uptake of subcutaneous sumatriptan in the rat: Implication for cluster headache treatment

et al. 2019

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“…In all subjects venoconstriction ended within 5-15 minutes; its intensity and duration were similar to that induced by 0.5-1 µg of 5-HT, as observed in a previous study. 13 Conversely, ergotamine provoked venoconstriction only at 50 µg doses (n=5). The venoconstriction induced by ergotamine was long lasting in all subjects and it did not decrease for at least one hour ( Figure 1).…”

Section: Resultsmentioning

confidence: 97%

“…The sumatriptan hand vein contraction was completely inhibited by low doses of ketanserin, a 5-HT 2 antagonist, indicating an action of the high doses of sumatriptan on the 5-HT 2 receptors. 13 In fact the 5-HT contraction of the hand vein is mediated by the 5-HT 2 receptors. 14,19,20 Ergotamine is not as effective as 5-HT, but more than sumatriptan, in provoking hand vein contraction.…”

Section: Discussionmentioning

confidence: 99%

Comparison Between Venoconstrictor Effects of Sumatriptan and Ergotamine in Migraine Patients

et al. 1994

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The vasoconstrictor activity of sumatriptan and ergotamine were compared by injecting these drugs in the hand vein of migraine subjects. We used the "venotest method", which permits the evaluation of the venoconstrictor effect of small doses of drugs, acting locally in the hand vein. Sumatriptan injected at increasing doses in the hand vein provoked contraction only at high doses (500 micrograms): venoconstriction lasted 5-15 minutes and was similar in intensity and duration to that induced by 0.5-1 micrograms of 5-hydroxytryptamine (5-HT). Likewise, ergotamine induced contraction only at a dose of 50 micrograms: this venoconstrictor effect was long lasting (at least 1 hour). Ergotamine-induced hand vein contraction, almost completely inhibited by ketanserin, seems mediated at least in part by 5-HT2 receptors, like the one induced by 5-HT and sumatriptan, already observed in a previous study. Clinical doses of ergotamine (0.25 mg intramuscular) and of sumatriptan (6 mg subcutaneous) do not provoke hand vein contraction for at least 1 hour: this could be due to a low activity of these drugs on the 5-HT2 vein receptors or a technique that is unsuitable to detect the vasoconstrictor effect of drugs given by the systemic route. The long lasting venoconstrictor effect of ergotamine may be due to a slow dissociation from receptor sites. The short vasoconstriction induced by sumatriptan could account for the recurrence of headache in many sumatriptan-treated migraine subjects.

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Serotonin and migraine: a reconsideration of the central theory

Panconesi¹

2008

J Headache Pain

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The 5-hydroxytryptamine (5-HT) has been implicated in migraine pathophysiology for the past 50 years. A low central 5-HT disposition associated with an increase in 5-HT release during attack is the most convincing change of 5-HT metabolism implicated in migraine. Peripheral studies on plasma/platelet have not generally shown low 5-HT levels. Studies on 5-HT reactivity showed hypersensitivity, also expressed as reduced tachyphylaxis (habituation), which successively was evidenced as the most characteristic marker of an altered sensory neurotransmission. Even the gender and seasonal variations of 5-HT parameters seem to agree with a low 5-HT turnover with receptoral hypersensitivity. The interpretation of the effects of some serotonergic drugs and recent neuroimaging studies give major evidence for this cascade of events. Although the exact mechanism that links abnormal 5-HT neurotransmission to the manifestation of head pain has yet to be fully understood, a deficit on 5-HT descending pain inhibitory system is still probably today the most implicated in migraine pathophysiology. This short review focuses and discusses the alteration of peripheral and central 5-HT parameters in migraine patients.

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Amplifying Effect of Sumatriptan on Noradrenaline Venoconstriction in Migraine Patients

Cited by 5 publications

References 28 publications

Ultra-rapid brain uptake of subcutaneous sumatriptan in the rat: Implication for cluster headache treatment

Ultra-rapid brain uptake of subcutaneous sumatriptan in the rat: Implication for cluster headache treatment

Comparison Between Venoconstrictor Effects of Sumatriptan and Ergotamine in Migraine Patients

Serotonin and migraine: a reconsideration of the central theory

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