Does sumatriptan cross the blood–brain barrier in animals and man?

Tfelt‐Hansen, Peer

doi:10.1007/s10194-009-0170-y

Cited by 58 publications

(34 citation statements)

References 71 publications

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“…This is a potential confounder of the data in that the drug may itself produce changes in brain structure and function, albeit intermittent use with the use with migraine attacks. While the direct effects of triptans are still a matter of debate (Tfelt-Hansen 2010), and longitudinal studies will be needed to clarify their impact on the central nervous system central nervous system central nervous system, there are studies supporting direct effects of triptans on CNS (Boshuisen and den Boer 2000; Cupini and Calabresi 2005; Dodick and Martin 2004). …”

Section: Discussionmentioning

confidence: 99%

Common hippocampal structural and functional changes in migraine

et al. 2012

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The hippocampus is classically involved in memory consolidation, spatial navigation and is involved in the stress response. Migraine is an episodic disorder characterized by intermittent attacks with a number of physiological and emotional stressors associated with or provoking each attack. Given that migraine attacks can be viewed as repeated stressors, alterations in hippocampal function and structure may play an important role in migraine pathophysiology. Using high-resolution magnetic resonance imaging, hippocampal morphometric and functional differences (in response to noxious heat stimulation) were compared in age and gender-matched acute episodic migraineurs with high (HF) versus low (LF) frequency of migraine attacks. Morphometric results were compared with age and gender-matched healthy control (HC) cohort. Significant larger bilateral hippocampal volume was found in LF group relative to the HF and HC groups suggestive of an initial adaptive plasticity that may then become dysfunctional with increased frequency. Functional correlates of greater deactivation (LF > HF) in the same hippocampal regions in response to noxious stimulation was also accompanied by overall reduction in functional connectivity of the hippocampus with other brain regions involved in pain processing in the HF group. The results implicate involvement of hippocampus in the pathophysiology of the migraine.

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Section: Discussionmentioning

confidence: 99%

Common hippocampal structural and functional changes in migraine

et al. 2012

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“…While sumatriptan has relatively limited blood-brain barrier (BBB) penetration, its brain/plasma partition coefficient of 0.13 suggests that central effects can occur as has been previously noted in humans and in animals (43). Additionally, as triptans are agonists for the 5-HT1 B/D receptors, central effects may occur even with low fractional receptor occupancy (58). Thus, it is conceivable that a period of prolonged sumatriptan exposure, as employed here, could lead to consequential levels of the drug within the brain to promote long-lasting central changes underlying cortical excitability.…”

Section: Discussionmentioning

confidence: 99%

Increased susceptibility to cortical spreading depression in an animal model of medication-overuse headache

Green

Felice

et al. 2013

Cephalalgia

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Objective The objective of this article is to evaluate electrically evoked thresholds for cortical spreading depression (CSD) and stress-induced activation of trigeminal afferents in a rat model of medication-overuse headache (MOH). Methods Sumatriptan or saline was delivered subcutaneously by osmotic minipump for six days to Sprague-Dawley rats. Two weeks after pump removal, animals were anesthetized and recording/stimulating electrodes implanted. The animals were pretreated with vehicle or topiramate followed by graded electrical stimulation within the visual cortex. CSD events were identified by decreased EEG amplitude and DC potential shift. Additional unanesthetized sumatriptan or saline-pretreated rats were exposed to bright light environmental stress and periorbital and hindpaw withdrawal thresholds were measured. Following CSD stimulation or environmental stress, immunohistochemical staining for Fos in the trigeminal nucleus caudalis (TNC) was performed. Results Sumatriptan pre-exposure significantly decreased electrical stimulation threshold to generate a CSD event. Topiramate normalized the decreased CSD threshold as well as stress-induced behavioral withdrawal thresholds in sumatriptan-treated rats compared to saline-treated animals. Moreover, CSD and environmental stress increased Fos expression in the TNC of sumatriptan-treated rats, and these effects were blocked by topiramate. Environmental stress did not elicit cutaneous allodynia or elevate TNC Fos expression in saline-treated rats. Conclusions A previous period of sumatriptan exposure produced long-lasting increased susceptibility to evoked CSD and environmental stress-induced activation of the TNC that was prevented by topiramate. Lowered CSD threshold, and enhanced consequences of CSD events (increased activation of TNC), may represent an underlying biological mechanism of MOH related to triptans.

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“…Similar discussions are ongoing for the triptans and gepants. There is no evidence that triptans may enter the human brain in sufficient quantities to exert central pharmacological actions [25,26] and binding of telcagepant within the brain could only be demonstrated after administration of supratherapeutic doses [27]. Thus, structures that are located outside the BBB appear to be more likely therapeutic targets for the CGRP antibodies.…”

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confidence: 93%