Ergot alkaloids block neurogenic extravasation in dura mater: Proposed action in vascular headaches

Saito, Kiyoshi; Markowitz, Stephen; Moskowitz, Mark A.

doi:10.1002/ana.410240607

Cited by 152 publications

(69 citation statements)

References 36 publications

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“…Like the ergot alkaloids (Saito et al, 1988) (Saito et al, 1988) + Indomethacin (Buzzi et al, 1989) + Aspirin (Buzzi et al, 1989) + neurogenic plasma extravasation within the dura mater. Although CGRP dilates cephalic blood vessels, it does not cause leakage in dura mater or extracranial tissues (Markowitz et al, 1987).…”

Section: Discussionmentioning

confidence: 99%

“…We have shown that the antimigraine drugs, ergotamine tartrate, dihydroergotamine and methysergide (given chronically) selectively block neurogenic plasma protein extravasation within dura mater without affecting leakage within extracranial vascular tissues, or the extravasation following systemic administration of SP or NKA (Saito et al, 1988). These antimigraine drugs readily pass the blood brain barrier (Ala-Hurula et al, 1979) and exhibit activity at 5-hydroxytryptamine (5-HT) receptors.…”

Section: Introductionmentioning

confidence: 99%

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The antimigraine drug, sumatriptan (GR43175), selectively blocks neurogenic plasma extravasation from blood vessels in dura mater

Buzzi

Moskowitz

1990

British J Pharmacology

404

192

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1We describe the actions of GR43175, a 5-hydroxytryptamine1 (5-HT,)-like receptor agonist, on neurogenically-mediated plasma protein extravasation within an important pain-sensitive intracranial tissue, the dura mater. 2 GR43175 markedly attenuated extravasation of '25I-albumin from blood vessels within ipsilateral dura mater when administered to rats (100 pgkg-1) fifteen minutes before unilateral electrical trigeminal stimulation (1.2 mA, 5Hz, Sims, S min.); the ratio (stimulated/unstimulated sides) decreased from 1.81 to 1.23, P < 0.005).3 GR43175 (l00pgkg-1, i.v., rats; 30pgkg-, i.v., guinea-pigs) decreased the leakage of radiolabelled albumin from 163% to 119% (P < 0.005, guinea-pig) or from 174 to 118% (P < 0.05, rat) above vehicletreated controls when injected ten minutes before systemic capsaicin treatment (0.5 or 1 umol kg-1, i.v.).4 GR43175 (30-300pgkg-1) did not block plasma protein extravasation within extracranial tissues of rats and guinea-pigs innervated by the trigeminal nerve (conjunctiva, eyelid and lip).5 The protein leakage which followed the i.v. administration of 5-HT (1 ymol kg 1) or neuropeptides which mediate neurogenic plasma extravasation, substance P (0.3 nmol kg-1 or 1 nmol kg 1) and neurokinin A (1 nmol kg-'), was not blocked by GR43175 (100, 300pgkg-1) despite the presence of leakage in amounts equivalent to that following neurogenic stimulation.6 GR43175 (l00gkg-1) decreased bradykinin (1Opmolkg-')-induced extravasation from 142 to 115% above vehicle-treated animals (P < 0.05). 7 These results demonstrate an important action of GR43175 on neurogenic mechanisms in dural blood vessels. Since the ergot alkaloids possess a similar profile of drug activity, it is suggested that drugs useful in the treatment of acute vascular headaches may share a similar mechanism of action.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The antimigraine drug, sumatriptan (GR43175), selectively blocks neurogenic plasma extravasation from blood vessels in dura mater

Buzzi

Moskowitz

1990

British J Pharmacology

404

192

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“…and dihydroergotamine (50,pg kg-1, i.v. or (Saito et al, 1988;. Secondly, dihydroergotamine (SOpgkg-1) and to a lesser extent sumatriptan (300pg kg-') attenuate the increases in immunoreactive calcitonin generelated peptide within sagittal sinus blood (e.g., venous effluent) during electrical stimulation of the trigeminal ganglion (Buzzi et al, 1991).…”

Section: Receptor Localizationmentioning

confidence: 99%

“…If closing arteriovenous shunts decreases vascular permeability following trigeminal stimulation, than leakage induced by intravenously administered neuropeptides (substance P or neurokinin A) should have been blocked as well. Constriction of arterioles (such as with phenylephrine) does not block neurogenic plasma extravasation nor does it reduce the increase in levels of calcitonin gene-related peptide in the sagittal sinus accompanying electrical stimulation (Saito et al, 1988;. Constriction of extracranial cephalic blood vessels follows ergotamine administration but neurogenic plasma extravasation is not blocked in these tissues.…”

Section: Receptor Localizationmentioning

confidence: 99%

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Further characterization of the putative 5‐HT receptor which mediates blockade of neurogenic plasma extravasation in rat dura mater

Buzzi

Moskowitz

Peroutka

et al. 1991

British J Pharmacology

Self Cite

102

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1 We describe the effects of pretreatment with 5-hydroxytryptamine (5-HT) receptor agonists and antagonists on neurogenically-mediated plasma protein extravasation (["25I]-albumin) in rat dura mater and in extracranial tissues (temporalis muscle fascia, conjunctiva, eyelid and lip) induced by electrical stimulation of the right trigeminal ganglion. 2 Leakage of [25I]-bovine serum albumin from blood vessels in dura mater following high intensity stimulation (1.2 mA, Sims, 5Hz for 5min) was significantly reduced by the intravenous administration of drugs active at 5-HT receptors with some selectivity for the 5-HT1 receptor subtypes: 5-carboxamidotryptamine (5-CT) (threshold dose, 1ngkg-1); 5-benzyloxytryptamine (5-BT) (10, 30 or 100augkg-1); 8-hydroxydipropylaminotetralin (8-OH-DPAT) (300pigkg-1); and as previously reported, sumatriptan (lOOpugkg -), dihydroergotamine (DHE) (SOugkg 1), ergotamine tartrate (lOO1ugkg 1) and chronically administered methysergide (1 mgkg-1).3 The putative 5-HT receptor antagonist, metergoline lOOpgkg-1, inhibited partially the effect of sumatriptan in dura mater providing additional evidence for a 5-HT1 receptor subtype-mediated mechanism, although it was not effective against 5-CT (1 ng kg-1). Methiothepin (300,ug kg-1) did not affect the response to sumatriptan. When administered at high concentrations (1 mg kg 1) methiothepin and metergoline decreased plasma protein extravasation in rat dura mater. 4 Pretreatment with the 5-HT2 receptor antagonists pizotifen, 300pugkg 1, or ketanserin, 300,ugkg ', or the 5-HT3 receptor antagonists MDL 72222, 300,ugkg-1, or ICS 205-930, 300pgkg-1, did not affect plasma protein leakage following electrical trigeminal stimulation. Blockade by sumatriptan of plasma protein extravasation was not inhibited by pizotifen (300,ug kg-1) or MDL 72222 (300pg kg-').5 The 5-HT receptor(s) mediating this response were present only on intracranial tissues innervated by the trigeminal nerve; plasma protein extravasation in extracranial tissues was not blocked by pretreatment with the equivalent or higher concentrations of the above drugs following low intensity trigeminal stimulation (0.1 mA, 5 ms, 5 Hz). 6 The putative 5-HT receptor(s) mediating this response were not present on sympathetic fibres innervating dura mater since unilateral removal of the superior cervical ganglion did not prevent the development of plasma protein extravasation nor did it affect the blockade by sumatriptan IOOpug kg-'. 7 The above pharmacological data suggest that intracranial vessels possess 5-HT receptor(s) which are coupled to inhibition of neurogenically-mediated plasma protein extravasation. These receptors cannot be detected on extracranial cephalic blood vessels innervated by the trigeminal nerve, although available evidence strongly suggests that the 5-HT receptors reside on perivascular trigeminal nerve fibres. The rank order of effective doses (threshold concentrations; 5-CT < 5-BT < DHE < sumatriptan < 8-OHDPAT) is most consistent with a 5-HTlB-or 5-HTlD-mediated response, ...

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The Aura-Headache Connection in Migraine

Spierings

2004

Arch Neurol

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A historical analysis is presented of insights into the pathogenetic mechanisms related to the migraine aura and headache and how the mechanisms connect. In the traditional sequential concept, advanced through the work of Edward Liveing, MD, Harold G. Wolff, MD, and others, the mechanisms are considered causally connected. A noncausal, parallel concept has been proposed as well and is considered in light of the results of recent animal experimental studies.

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Ergot alkaloids block neurogenic extravasation in dura mater: Proposed action in vascular headaches

Cited by 152 publications

References 36 publications

The antimigraine drug, sumatriptan (GR43175), selectively blocks neurogenic plasma extravasation from blood vessels in dura mater

The antimigraine drug, sumatriptan (GR43175), selectively blocks neurogenic plasma extravasation from blood vessels in dura mater

Further characterization of the putative 5‐HT receptor which mediates blockade of neurogenic plasma extravasation in rat dura mater

The Aura-Headache Connection in Migraine

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