Role of Some Biogenic Substances in Migraine and Relevant Mechanism in Antimigraine Action of Ergotamine‐studies in an Experimental Model for Migraine

Self Cite

1 Though it is well known that the antimigraine drugs ergotamine and dihydroergotamine reduce carotid arteriovenous anastomotic shunting, it is uncertain whether a 5-HT1-like receptor is responsible for this effect. Using a high dose of methiothepin (3 mg kg-1), which completely blocks the carotid vascular effects of sumatriptan, we have attempted to study the role of 5-HT1-like receptors in the carotid vascular effects of ergotamine as well as dihydroergotamine in anaesthetized pigs. 2 Both ergotamine and dihydroergotamine increased arterial blood pressure and decreased heart rate. 3 The ergot alkaloids reduced dose-dependently total carotid blood flow and conductance as a result of a selective decrease in the arteriovenous anastomotic fraction. The nutrient fraction increased, particularly to bones, tongue and salivary glands with ergotamine and to ears, head skin, bones and salivary glands with dihydroergotamine. In contrast, dural vascular conductance tended to decresae. 4 Methiothepin (3mg kg-') partially antagonized the decrease in total carotid and arteriovenous anastomotic blood flow and conductance by the ergot alkaloids; the ED30 for ergotamine and dihydroergotamine (agonist dose eliciting a 30% decrease in arteriovenous anastomotic conductance) was raised by 3.1 and 5.2 fold respectively. 5 These results indicate that the effects of ergotamine and dihydroergotamine are partly mediated by methiothepin-sensitive receptors, which may probably belong to either 5-HT1-like or a2-adrenoceptor category. However, an important part of the effect of ergot alkaloids is left after methiothepin and this could be mediated by other, perhaps novel, receptors.

Section: Systemic Haemodynamicssupporting

confidence: 63%

Section: Carotid Haemodynamicsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Carotid vascular effects of ergotamine and dihydroergotamine in the pig: no exclusive mediation via 5‐HT₁‐like receptors

Boer

Heiligers

Saxena

1991

Self Cite

“…Effects of5-hydroxytryptamine in the carotid vascular bed Intracarotid infusions of 5-HT, as we have also found with bolus injections in cervical sympathectomized dogs (Saxena etal., 1971;Saxena, 1972;Saxena & de Vlaam-Schluter, 1974), resulted in a reduction of total carotid blood flow in our pigs. Despite this reduction, tissue blood flow, particularly to the skin and ears (their colour changed to bright red), increased and the AVAs constricted.…”

Section: Discussionmentioning

confidence: 99%

Effects of methysergide and 5‐hydroxytryptamine on carotid blood flow distribution in pigs: further evidence for the presence of atypical 5‐HT receptors

Saxena

Verdouw

1984

Self Cite

1 The effects of acute (50-350 gg kg-, i.v.) and subacute (350 gg kg-l orally per day for six days) administration of methysergide, and of intra-arterial infusions of 0.5 and 2.0 gkg-min-1 5-hydroxytryptamine (5-HT) on the distribution of carotid blood flow into the capillary (nutrient) and arterio-venous anastomotic (AVA) fractions were studied in anaesthetized pigs. 2 The acute, but not the subacute, administration of methysergide caused a moderate reduction of carotid blood flow. This reduction, noticed only in the AVA fraction, was due to a constriction of the arterio-venous anastomoses (AVAs). 3 Both doses of 5-HT reduced total carotid blood flow but its nutrient fraction -particularly that distributed to the skin and ears -increased substantially. The AVA fraction was greatly diminished. 4 After treatment with methysergide, 5-HT no longer reduced the total carotid blood flow, but increased it. Despite this reversal the constriction of AVAs by the amine was only slightly diminished. On the other hand, the vasodilatation of the nutrient channels was enhanced. 5 The results of the interaction between methysergide and 5-HT provide further evidence for the presence of 'atypical' 5-HT receptors (probably corresponding to 5-HT1 binding sites) mediating AVA contraction and nutrient vasodilatation. The 5-HT2 receptors mediate vasoconstriction and are located in the large conducting arteries and possibly, in smaller numbers, in the AVAs and arterioles.

“…and above) did produce a small bradycardia which may be centrally mediated (Coote et al, 1987). The most prominent effect of GR43175 was to produce a highly selective vasoconstriction within the carotid arterial circulation, an action which is shared by the antimigraine drugs, ergotamine and methysergide (Saxena, 1974;Saxena & de Vlaam-Schluter, 1974). However ergotamine, unlike GR43175, also causes marked increases in blood pressure, total peripheral, mesenteric, vertebral and coronary vascular resistance (Saxena & de VlaamSchluter, 1974).…”

Section: Discussionmentioning

confidence: 99%

The selective carotid arterial vasoconstrictor action of GR43175 in anaesthetized dogs

Feniuk

Humphrey

Perren

1989

139

1 GR43175 is a highly selective agonist at 5-HTI-like receptors in the dog saphenous vein. This study describes the haemodynamic effects of GR43175 in barbitone-anaesthetized dogs. 2 GR43175 (1-lOOOpgkg-1, i.v.) produced dose-dependent decreases in carotid arterial blood flow with little or no change in arterial blood pressure. The decrease in blood flow was associated with an increase in carotid arterial vascular resistance. In preliminary studies, the dose of GR43175 producing 50% of the maximum carotid vasoconstrictor response was 39 + 8 jig kg-1, i.v. 3 In comparative regional haemodynamic studies, GR43175 (1-1000igkg-', i.v.) had little effect on total peripheral resistance or resistance in the mesenteric, vertebral and coronary arterial vascular beds. Low doses of GR43175 decreased, whilst high doses (100 pg kg-1, i.v. and above) increased femoral arterial vascular resistance. GR43175 (1-lOOOpgkg-1, i.v.) had no effect on respiratory inflation pressure. In doses of lOOpgkg-1 i.v. and above, GR43175 caused small decreases in heart rate.4 The carotid arterial vasoconstrictor action of GR43175 was resistant to antagonism by the 5-HT2 receptor, 5-HT3 receptor and x-adrenoceptor blocking drugs, ketanserin, MDL72222 and phentolamine respectively, but could be antagonized by the non-selective 5-HT1-like receptor blocking drug methiothepin. Methiothepin had no effect on the carotid vasoconstrictor action of the thromboxane A2 mimetic, U46619. 5 The results demonstrate that GR43175 produces a selective vasoconstriction in the carotid arterial circulation of anaesthetized dogs via activation of 5-HT,-like receptors, which appear similar to those mediating contraction of the dog isolated saphenous vein.