Effects of Sumatriptan on Cerebral Blood Flow Under Normo- and Hypercapnia in Rats

Fukuda, Michinari; Suzuki, Noriyuki; Maruyama, Shigeyoshi; Dobashi, Kazushige; Kitamura, Akihiko; Sakai, Fumihiko

doi:10.1046/j.1468-2982.2002.00395.x

Cited by 6 publications

(3 citation statements)

References 26 publications

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“…A second jpet.aspetjournals.org major finding in the present study is that donitriptan was devoid of significant vasoconstrictor effects in any of the cranial regional vascular beds investigated. This observation is corroborated by a report from another group, in which similar results on cerebral blood flow were described in rats after intracarotid administration of sumatriptan (Fukuda et al, 2002). In our study, the fluorescent microsphere technique was chosen for the determination of regional blood flow.…”

supporting

confidence: 86%

Donitriptan Decreases Jugular Venous Oxygen Saturation in Rats in the Absence of Cranial Vasoconstriction: An Overlooked Mechanism of Antimigraine Action?

Létienne

Blanchet²,

Sole³

et al. 2005

J Pharmacol Exp Ther

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The aim of the present study was to determine whether donitriptan and sumatriptan decreased jugular venous oxygen saturation and increased carbon dioxide partial pressure in venous blood. However, previous studies conducted with these compounds cannot discriminate whether the decrease of venous oxygen saturation is dependent of cranial vasoconstrictor. In the present study, vehicle (n ϭ 10), donitriptan (2.5, 10, and 40 g/kg; n ϭ 8) or sumatriptan (630 g/kg; n ϭ 8) were infused into the carotid artery in the anesthetized rat. Regional blood flows were evaluated in the presence of donitriptan (10 g/kg; n ϭ 6) or vehicle (n ϭ 6). Jugular venous oxygen saturation was significantly decreased by donitriptan (from 10 g/kg) with maximal changes of Ϫ32.9 Ϯ 8.0%. Jugular carbon dioxide partial pressure was increased by donitriptan, reaching maximal changes of 17.7 Ϯ 4.6% (P Ͻ 0.05 versus vehicle). Similarly, sumatriptan significantly decreased venous oxygen saturation and increased jugular carbon dioxide partial pressure. These changes induced by donitriptan are abolished by the 5-hydroxytryptamine (5-HT) 1B/1D receptor antagonist. In addition, donitriptan was devoid of significant effects on systemic arterial pressure, heart rate, or regional blood flows, including systemic arterial-jugular venous anastomotic, systemic, or cranial. The results demonstrate that donitriptan increases cerebral oxygen consumption by 5-HT 1B/1D receptor activation in the absence of cranial vasoconstriction.The current mechanism(s) of action of 5-HT 1B/1D receptor agonists (triptans) in the acute relief of migraine headache is considered to comprise cranial vasoconstriction (Humphrey and Feniuk, 1991), peripheral neuronal inhibition (Moskowitz, 1992), and inhibition of transmission through secondorder neurons of the trigeminocervical complex (Hoskin et al., 1996), leading to inhibition of the effects of activated nociceptive terminal afferents (Goadsby, 2000). Donitriptan, which has been evaluated for efficacy in the acute relief of migraine headache in phase II clinical trials (Dukat, 2001), and other triptans (Létienne et al., 2003a) augmented cerebral oxygen utilization and tissue metabolism. This additional mechanism of action may also be relevant to the acute headache-relieving effects of triptans as a whole. However, our previous studies in the anesthetized pig (Létienne et al., 2003a,b) showed that the triptans increased arteriovenous oxygen saturation difference and carbon dioxide partial pressure in venous blood draining the head but also produced concomitant carotid vasoconstriction. Consequently, it was not possible to determine whether these events occurred independently.The aim of the present investigation was therefore to determine whether donitriptan and sumatriptan produced similar effects on jugular venous blood gas parameters in a model in which triptans are considered not to produce cranial vasoconstriction. Thus, the study was performed in anestheArticle, publication date, and citation information can be found at

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supporting

confidence: 86%

Donitriptan Decreases Jugular Venous Oxygen Saturation in Rats in the Absence of Cranial Vasoconstriction: An Overlooked Mechanism of Antimigraine Action?

Létienne

Blanchet²,

Sole³

et al. 2005

J Pharmacol Exp Ther

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“…In vivo , psilocybin undergoes first pass metabolism to psilocin, the active metabolite thought to account for most of the psychotropic effects of psilocybin administration ( Hasler et al., 1997 , Passie et al., 2002 ). A further potential confound in interpretation of BOLD signals in the case of psilocin is the combined neuronal and vascular effects of serotonergic drugs ( Cohen et al., 1996 , Fukuda et al., 2002 ). The 5-HT 2A receptor has vasoconstrictive effects ( Kovács et al., 2012 , Martin, 1994 ), and psilocin also has affinity for the 5-HT 1D and 5-HT 1B receptors ( Halberstadt and Geyer, 2011 ), which have both neuronal and vascular effects ( Gupta and Villalón, 2010 , Kovács et al., 2012 ).…”

Section: Introductionmentioning

confidence: 99%

Neurovascular and neuroimaging effects of the hallucinogenic serotonin receptor agonist psilocin in the rat brain

et al. 2015

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The development of pharmacological magnetic resonance imaging (phMRI) has presented the opportunity for investigation of the neurophysiological effects of drugs in vivo. Psilocin, a hallucinogen metabolised from psilocybin, was recently reported to evoke brain region-specific, phMRI signal changes in humans. The present study investigated the effects of psilocin in a rat model using phMRI and then probed the relationship between neuronal and haemodynamic responses using a multimodal measurement preparation. Psilocin (2 mg/kg or 0.03 mg/kg i.v.) or vehicle was administered to rats (N = 6/group) during either phMRI scanning or concurrent imaging of cortical blood flow and recording of local field potentials. Compared to vehicle controls psilocin (2 mg/kg) evoked phMRI signal increases in a number of regions including olfactory and limbic areas and elements of the visual system. PhMRI signal decreases were seen in other regions including somatosensory and motor cortices. Investigation of neurovascular coupling revealed that whilst neuronal responses (local field potentials) to sensory stimuli were decreased in amplitude by psilocin administration, concurrently measured haemodynamic responses (cerebral blood flow) were enhanced. The present findings show that psilocin evoked region-specific changes in phMRI signals in the rat, confirming recent human data. However, the results also suggest that the haemodynamic signal changes underlying phMRI responses reflect changes in both neuronal activity and neurovascular coupling. This highlights the importance of understanding the neurovascular effects of pharmacological manipulations for interpreting haemodynamic neuroimaging data.

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“…The 5-HT 1B/1D receptor agonist sumatriptan attenuates experimentally induced cerebral hyperperfusion in both rat 70 and baboon 71 models, whilst having no effect on blood flow at normal flow volumes. In patients with migraine it causes vasoconstriction of the internal carotid and middle cerebral arteries 72,73 without inducing changes in systemic cardiovascular parameters.…”

Section: Potential Interventions For Patients Believed To Be At High mentioning

confidence: 97%

Intracerebral Haemorrhage Following Carotid Endarterectomy

RUSSELL¹,

GOUGH²

2004

European Journal of Vascular and Endovascular Surgery

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Objectives. To determine risk factors for the development of hyperperfusion and intra-cerebral haemorrhage following carotid endarterectomy and formulate potential protocols for prevention. Methods. MEDLINE database search of the English language literature (1966-2002) was performed using the words 'cerebral haemorrhage', 'intracranial haemorrhage' and 'carotid endarterectomy'. Other articles were cross-referenced by hand. Results. There are no data from randomised trials confirming the significance of any single risk factor. The evidence suggests that the following may have a role: pre-operative hypertension, recent ipsilateral non-haemorrhagic stroke, previous ischaemic cerebral infarction, surgery for a. 90% ipsilateral internal carotid artery (ICA) stenosis, impaired cerebrovascular reserve, intra-operative haemodynamic or embolic ischaemia, post-operative hypertension, an ipsilateral increase of $175% in peak middle cerebral artery velocity (MCAV) and/or a $100% increase in pulsatility index. Conclusions. A critical ICA stenosis with impaired cerebrovascular reserve resulting in maximal intracerebral vasodilatation and post-operative hyperperfusion (impaired autoregulation) appear to be central to the development of ICH. Appropriate pre-operative screening and post-operative monitoring in high risk patients might identify those who would benefit from manipulation of the haemodynamic events that appear to promote ICH.

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Effects of Sumatriptan on Cerebral Blood Flow Under Normo- and Hypercapnia in Rats

Cited by 6 publications

References 26 publications

Donitriptan Decreases Jugular Venous Oxygen Saturation in Rats in the Absence of Cranial Vasoconstriction: An Overlooked Mechanism of Antimigraine Action?

Donitriptan Decreases Jugular Venous Oxygen Saturation in Rats in the Absence of Cranial Vasoconstriction: An Overlooked Mechanism of Antimigraine Action?

Neurovascular and neuroimaging effects of the hallucinogenic serotonin receptor agonist psilocin in the rat brain

Intracerebral Haemorrhage Following Carotid Endarterectomy

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