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PubMed1981

Effect of caffeine on ergotamine absorption from rat small intestine.

The effect of caffeine on the absorption of ergotamine from the rat small intestine was studied. The results of a series of experiments showed that caffeine significantly enhanced absorption of ergotamine from solutions of pH 5.0 when both substances were in solution and when an intact blood supply was either absent (in vitro everted sac experiments) or present (in situ experiments). Caffeine did not appear to influence the absorption rate of ergotamine in situ experiments when the solution pH was 3.0. Isosorbide dinitrate, a vasodilator, enhanced ergotamine absorption when both substances were administered simultaneously into intestinal loops in situ. Isosorbide dinitrate probably exerts its effect by increasing blood flow to the intestine. The results are consistent with an hypothesis that the rate-determining step in ergotamine absorption is the transport of the drug from a lipid phase (GI membrane) into an aqueous phase (blood). Caffeine is thought to exert its rate-accelerating effect by increasing the water solubility of ergotamine neutral molecules.

Animals↗
PubMed1983

Influence of pizotifen and ergotamine on the venoconstrictor effect of 5-hydroxytryptamine and noradrenaline in man.

The influence of locally infused pizotifen (80 ng) and ergotamine (16 ng and 4 ng) on the compliance of superficial hand veins in man, and their interactions with the venoconstrictor effects of noradrenaline and 5-hydroxytryptamine (5-HT), were investigated in a placebo-controlled study in healthy volunteers. Pizotifen alone reduced venous compliance and produced a parallel displacement to the right of the 5-HT dose-response curve suggestive of competitive antagonism. The venoconstrictor effect of noradrenaline was not influenced by pizotifen. This confirms the selective antagonism of 5-HT by pizotifen and supports the existence of specific 5-HT receptors on human veins. After infusion of 16 ng ergotamine, which by itself reduced venous compliance, the venoconstrictor effects of the lower doses of 5-HT and of all doses of noradrenaline were larger but still never exceeded the arithmetic sum of the separate effects of noradrenaline or 5-HT and ergotamine. A lower dose of ergotamine (4 ng) induced only a small venoconstriction and did not influence the constrictor effect of noradrenaline. Therefore, in contrast to previous observations, no potentiation of the venoconstrictor effect of noradrenaline by ergotamine was observed under the present experimental conditions. The additive effect of noradrenaline and ergotamine may well explain its therapeutic action in the treatment of migraine.

Adult↗
PubMed1997

Acute upper extremity ischemia during concomitant use of ergotamine tartrate and ampicillin.

Individual hypersensitivity to the vasoconstrictor effects of ergotamine tartrate has been observed even at doses within recommended limits. Hypersensitivity can be induced by concomitant use with other drugs. The best-documented example of drug-induced hypersensitivity to ergotamine tartrate involves antibiotics of the macrolides class. The mechanism underlying this interaction appears to be interference with metabolism of ergotamine tartrate by the liver. In the present report we describe a case of upper extremity ischemia during concomitant use of ergotamine tartrate and ampicillin. The fact that the effect was not dose-dependent, disappeared when administration of ampicillin was discontinued, and reappeared when administration of ampicillin was resumed suggests that the underlying mechanism in our patient was immunologic. Since immunologic hypersensitivity to the vasoconstrictor effects of ergotamine tartrate is unpredictable, great caution and close surveillance is advisable when ergotamine tartrate is used in association with other drugs.

Ampicillin↗
PubMed1988

Effects of ergotamine on cardiovascular catecholamine receptors in the pithed rat.

1. Ergotamine (3-10 micrograms/kg) inhibited the electrical stimulation-induced pressor and cardiac responses without modifying pressor responses of noradrenaline and tyramine in the pithed rat. 2. Yohimbine (0.3 mg/kg) partially prevented the ergotamine cardiac and vascular inhibitory effects but sulpiride (0.3 mg/kg) only prevented it at vascular level. Both antagonists together abolished the ergotamine inhibition of electrical stimulation-induced pressor responses. 3. The cumulative dose-response curve of ergotamine (1-100 micrograms/kg) vasoconstrictor effects was partially inhibited to the same extent by prazosin (1 mg/kg) and yohimbine (0.3 mg/kg). A greater inhibition was observed with both antagonists administered together. 4. Ergotamine (30 micrograms/kg), in presence of yohimbine, inhibited the pressor responses of methoxamine, without any effect on xylazine pressor responses. 5. These data indicate that ergotamine acts as an agonist of both the presynaptic dopamine receptors and alpha 2-adrenoceptors, of alpha 1 and alpha 2-postsynaptic adrenoceptors, and also as an antagonist of the postsynaptic alpha 1-adrenoceptors.

Animals↗
PubMed2000

Contractile responses to sumatriptan and ergotamine in the rabbit saphenous vein: effect of selective 5-HT(1F) receptor agonists and PGF(2alpha).

Contractile responses to ergotamine, sumatriptan and the novel 5-HT(1F) receptor agonists, LY334370 and LY344864 were examined using the rabbit saphenous vein. Ergotamine (pEC(50)=8.7+/-0.06) was 30 fold more potent than 5-hydroxytryptamine (5-HT) (pEC(50)=7.2+/-0.13) and 300 fold more potent than sumatriptan (pEC(50)=6.0+/-0.08) in contracting the rabbit saphenous vein in vitro. The selective 5-HT(1F) receptor agonists, LY334370 or LY344864 (up to 10(-4) M), did not contract the rabbit saphenous vein. The contractile response to ergotamine in this tissue resulted from activation of both alpha(1) and 5-HT(1B/1D) receptors based on the observation that prazosin (10(-6) M), an alpha-adrenoceptor antagonist, and GR127935 (10(-8) M) a 5-HT(1B/1D) receptor antagonist, dextrally shifted the contractile response to ergotamine. In contrast, prazosin (10(-6) M) did not alter contraction to sumatriptan whereas GR127935 (10(-8) M) was a potent antagonist (-log K(B)=10.0) suggesting that sumatriptan-induced contraction of the rabbit saphenous vein was mediated only by activation of receptors similar or identical to 5-HT(1B/1D) receptors. PGF(2alpha) (3x10(-7) M) produced a modest increase (approximately 5.0 - 10.0% maximum PGF(2alpha) contraction) in saphenous vein force. Precontraction with PGF(2alpha) (3x10(-7) M) dramatically augmented the potency and maximal contractile response to sumatriptan (pEC(50)=7.1) and modestly enhanced the contractile potency of ergotamine (pEC(50)=9.0) in the rabbit saphenous vein. However, PGF(2alpha) (3x10(-7) M) only unmasked a contraction to the 5-HT(1F) receptor agonists when concentrations exceeded 10(-5) M, concentrations considerably higher than their 5-HT(1F) receptor affinities. LY334370 (10(-6) M) pretreatment did not alter contraction to either sumatriptan or ergotamine and a higher concentration (10(-5) M) of LY334370 or LY344864 inhibited contraction to sumatriptan. Thus, activation of 5-HT(1F) receptors will not induce vascular contraction (either alone or following modest tone with PGF(2alpha)) or augment contraction to other contractile agonists in the rabbit saphenous vein.

Animals↗
PubMed1983

Ergotamine-induced constriction of cranial arteriovenous anastomoses in dogs pretreated with phentolamine and pizotifen.

Previous investigations from our laboratory have shown that ergotamine causes a selective vasoconstriction in the carotid vascular bed of the dog and that the drug constricts arteriovenous anastomoses (AVAs) in cats and pigs. Since ergotamine can act via alpha-adrenergic or D-serotonergic receptors in certain vascular and non-vascular tissues, we have attempted to ascertain here if these receptors mediate the constriction of AVAs. Using radioactive microspheres of 15 microns diameter we found in the dog that about 40% of the carotid arterial blood is shunted to the venous side via AVAs. Ergotamine (2-20 micrograms X kg-1, i.v.) reduced total carotid blood flow to a larger extent in the AVA part than in the extracerebral part (muscles, ears, skin and fat). The cerebral component of carotid blood did not change. These results, confirming that ergotamine decreases arteriovenous shunting, show that the drug has a more selective action on the AVAs than on the arterioles. Pretreatment with phentolamine (0.5 mg X kg-1), pizotifen (0.5 mg X kg-1) or their combination did not effectively modify the responses to ergotamine. It is concluded that the vasoconstriction of cranial AVAs (and arterioles) by ergotamine does not appear to be primarily mediated by either alpha-adrenergic or D-serotonergic receptors. However, the role of atypical serotonin receptors has yet to be determined.

Animals↗
PubMed1980

[Non-invasive method for recognition of coronary artery spasm: 201thallium sequential scintigraphy of the myocardium after ergotamine provocation (author's transl)].

For evaluation of coronary artery spasm 201thallium sequential scintigraphy of the myocardium after ergotamine provocation was performed in 10 patients with recurrent angina pectoris at rest and normal exercise ECG. In 9 out of the 10 patients ergotamine administration in the same dosage was repeated during the coronary angiography. A reversible defect in the 201thallium scintigram representative of regional myocardial ischaemia developed in 9 patients after ergotamine. Only in 4 out of the 9 patients angina pectoris and ST elevation were present at the same time. In all cases coronary spasm after ergotamine was demonstrable in the coronary angiogram; in the 4 patients with ergotamine-induced Prinzmetal angina pectoris it consisted of complete vascular occlusion, in the asymptomatic patients of incomplete vascular narrowing of a higher degree. In all cases the spasm could be relieved by ergotamine antidotes within a few minutes.

Adult↗
PubMed1989

Reduction of cephalic arteriovenous shunting by ergotamine is not mediated by 5-HT1-like or 5-HT2 receptors.

1. The potent, antimigraine drug ergotamine has affinity for both 5-HT1 and 5-HT2 binding sites and constricts arteriovenous anastomoses. Since 5-HT also constricts arteriovenous anastomoses (mainly via 5-HT1-like receptors), this study investigates the involvement of 5-HT receptors in the ergotamine-induced reduction of arteriovenous shunting in the carotid circulation of the cat and pig. 2. In the cat, ergotamine (3, 10 and 30 micrograms kg-1, i.v.) reduced carotid blood flow, predominantly by a reduction in arteriovenous anastomotic blood flow. Pretreatment with ketanserin (0.5 mg kg-1, i.v.) or methiothepin (1 mg kg-1, i.v.) did not antagonize the effects of ergotamine. 3. In the pig, ergotamine (2.5, 5, 10 and 20 micrograms kg-1, i.v.) also reduced carotid blood flow and arteriovenous shunting, which was not affected by pretreatment with methiothepin (1 mg kg-1, i.v.). 4. These results suggest that the reduction by ergotamine in the shunting of carotid arterial blood via cephalic arteriovenous anastomoses is not mediated by 5-HT1-like or 5-HT2 receptors.

Animals↗
PubMed1991

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

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 decrease. 4. Methiothepin (3 mg kg-1) 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 alpha 2-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.

Animals↗
PubMed1996

Endothelial 5-HT receptors mediate relaxation of porcine pulmonary arteries in response to ergotamine and dihydroergotamine.

1. The aim of the present study was to investigate whether antimigraine ergot compounds may act at endothelial 5-hydroxytryptamine (5-HT) receptors which trigger the release of endothelium-derived relaxing factor (EDRF). Changes in tone of porcine isolated pulmonary arteries were measured isometrically. The integrity of the endothelium was assessed by the bradykinin-induced relaxation of prostaglandin F2 alpha (PGF2 alpha, 3 microM)-precontracted vessels. 2. The ergot derivatives ergotamine, dihydroergotamine (DHE) and dihydroergocristine, as well as 5-HT and (+/-)-alpha-methyl-5-HT, elicited a reversible endothelium-dependent relaxation of PGF2 alpha-precontracted arterial ring segments. The relaxation to both ergotamine and 5-HT was associated with an increase in cyclic GMP. After pretreatment of the vessels with NG-nitro-L-arginine methyl ester (200 microM), or removal of endothelium by mechanical rubbing, the relaxant responses were abolished. 3. The mean pEC50 values for relaxant responses followed the order: (+/-)-alpha-methyl-5-HT (8.80) > 5-HT (8.75) > ergotamine (8.17) > DHE (7.70) > 5-carboxamidotryptamine (7.62) > dihydroergocristine (7.17). 4. The relaxant effects of both ergotamine and dihydroergotamine were resistant to block by indomethacin (3 microM), prazosin (1 microM) and ketanserin (1 microM). However, the ergotamine-induced relaxation was highly susceptible to block by pizotifen (pA2 = 8.23), norclozapine (pA2 = 8.20), methiothepin (-log IC50 = 7.26), rauwolscine (pA2 = 7.24) and mesulergine (pA2 = 6.64). Each antagonist inhibited the relaxant responses to (+/-)-alpha-methyl-5-HT in the same manner with similar potency as that determined against ergotamine. 5. Recently, mRNA transcripts for 5-HT1D beta and 5-HT2B receptors have been demonstrated in porcine pulmonary arteries. The rank order of potencies of agonists and antagonists in the present study suggests that the relaxant responses to 5-HT and ergot derivatives are mediated through activation of endothelial 5-HT receptors which are similar to the 5-HT2B receptor subtypes.

Adrenergic alpha-Antagonists↗
PubMed1993

No effect of the 5HT2-antagonist ICI 169,369 on systolic, ergotamine-induced blood pressure changes in man.

The 5HT-antagonistic effect of drugs in man is difficult to study because of side effects to 5HT. Ergotamine, however contracts human arteries, probably by acting on 5HT receptors. This effect can be antagonized in vitro by the 5HT antagonist ICI 169,369. After an initial ergotamine challenge to select responders to ergotamine, 10 selected volunteers were given in a double blind study an oral dose of either placebo, 30 mg or 120 mg of ICI 169,369. After 2 hr an intravenous dose of 0.5 mg ergotamine tartrate was given. From 6 to 8 hr after the administration, ergotamine caused a mean decrease in the toe-arm systolic gradient, measured by strain-gauge plethysmography of 32 mmHg (P < 0.001), which was not influenced by either 30 mg or 120 mg ICI 169,369 (P < 0.4). The most likely explanation for our inability to detect any effect of ICI 169,369 on blood pressure changes, induced by ergotamine may be high binding (99%) of ICI 169,369 to plasma proteins. There was, however, indication of a per se vasodilatory effect of ICI 169,369 since the dose of 120 mg increased the toe-arm systolic gradient by 4.7 mmHg.

Administration, Oral↗
PubMedDate not supplied

The effect of ergotamine and dihydroergotamine on cerebral blood flow in man.

The effects of ergotamine and dihydroergotamine on cerebral blood flow was investigated 4 hours after i.v. injection as these drugs might be of importance for migraine treatment. Eight normal male volunteers (not suffering from migraine) received 0.5 mg ergotamine and 1 mg dihydroergotamine i.v. Cerebral blood flow was measured by the xenon-133 inhalation method and single-photon-emission computerized tomography before and after intravenous acetazolamide administration (1 g). Cerebral blood flow was measured before and 4 hours after ergotamine and dihydroergotamine administration. Strain-gauge measurements of toe-arm systolic gradients were used to monitor the effect of the drug on leg arteries. Mean hemispheric and regional cerebral blood flow was unchanged after either drug (mean +/- SEM, ml/100 g/min): for ergotamine, 57 +/- 3 before and 57 +/- 3 at 4 hours; for dihydroergotamine, 54 +/- 2 before and 55 +/- 2 at 4 hours. The acetazolamide response was unchanged as well. Only ergotamine decreased the toe-arm systolic gradient significantly (22 mm Hg at maximum after 240 minutes; p less than 0.02). Thus, our study did not support the belief that ergot alkaloids should be withheld from patients during attacks of classic migraine, but this has to be investigated further. The discrepancy in the peripheral effects of ergotamine and dihydroergotamine might also be of clinical importance.

Acetazolamide↗
PubMed2001

Ergotamine, dihydroergotamine: current uses and problems.

In randomized clinical trials oral ergotamine was found superior to placebo but inferior to oral sumatriptan 100mg. In contrast rectal ergotamine was found to have higher efficacy (73% headache relief) than rectal sumatriptan (63% headache relief). Intranasal dihydroergotamine (DHE) was found superior to placebo but less effective than subcutaneous and intranasal sumatriptan. In general, the use of the more specific drugs, the triptans, causing less adverse events and being more effective, is preferable to the use of the ergotamine in the acute treatment of migraine. If ergotamine is to be used the rectal route is preferable. The rectal dose of ergotamine should be tailored to the individual patient. The intranasal dose of DHE , between 1 and 2 mg, should also be tailored to the individual patient. In order to avoid drug-induced headache ergotamine and DHE should not be used daily.

Analgesics, Non-Narcotic↗
PubMed2006

Risk of ischemic complications related to the intensity of triptan and ergotamine use.

OBJECTIVE: To investigate whether the intensity of triptan and ergotamine use, in specific overuse, is associated with the risk of ischemic complications. METHODS: We conducted a retrospective nested case-control study using data from the PHARMO Record Linkage System. All patients with more than one prescription for either a triptan or ergotamine were initially identified. Cases were all patients who were admitted to the hospital for an ischemic complication. Matched controls were assigned the same index date as the cases. The determinant was the intensity of use of triptans and ergotamine during 1 year preceding the index date. Overuse was defined as use of > or =90 defined daily doses during that year. Conditional logistic regression was used to estimate odds ratios (ORs), adjusting for confounders. Stratified analysis was used to estimate the risk for both patients using and those not using cardiovascular drugs. RESULTS: A total of 17,439 patients received more than one prescription. A total of 188 cases and 689 controls were identified. Triptan overuse was not associated with an increased risk of ischemic complications (OR 0.96; 95% CI: 0.49 to 1.90). Overuse of triptans in patients concomitantly using cardiovascular drugs did not increase this risk. Overuse of ergotamine turned out to be a risk factor for ischemic complications (OR 2.55; 95% CI: 1.22 to 5.36). Patients overusing ergotamine and concomitantly using cardiovascular drugs were at highest risk (OR 8.52; 95% CI 2.57 to 28.2). CONCLUSIONS: In general practice, triptan overuse does not increase the risk of ischemic complications. Overuse of ergotamine may increase the risk of these complications, especially in those simultaneously using cardiovascular drugs.

Adolescent↗
PubMed1997

Plasma concentrations of prolactin, growth hormone, and luteinizing hormone in steers administered ergotamine or ergonovine.

This research investigated whether ergot alkaloids associated with endophyte-infected tall fescue could alter plasma concentrations of pituitary hormones that regulate biological processes related to cattle performance. Seven Angus yearling steers received single i.v. injections of ergotamine tartrate, ergonovine maleate, or saline vehicle in a simple cross-over design. Each steer was given a different compound each week. Blood samples were collected at 15-min intervals for 45 min before and 240 min after treatments to assess plasma concentrations of prolactin, growth hormone, and LH. Respiratory rates were measured hourly to ascertain a systemic effect. Ambient temperature averaged 34 degrees C during data collection. Treatment x time was a significant source of variation for respiration rate and plasma concentrations of each hormone evaluated. Respiration rates were higher for ergonovine than for saline (P < .02) and ergotamine (P < .07) 30 min after treatment, but they were higher (P < .05) for ergotamine than for ergonovine and saline by 210 min after treatment. Both alkaloids transiently elevated (P < .01) plasma growth hormone concentrations compared with before alkaloid treatment and after saline treatment. Ergotamine reduced (P < .01) plasma concentrations of prolactin and LH throughout the 120-min period after treatment compared with concentrations before ergotamine treatment and after saline treatment. Ergonovine lowered (P < .01) prolactin concentrations for a shorter time than ergotamine and did not affect mean LH concentrations. Results indicated that ergot alkaloids implicated as contributing agents to fescue toxicosis can alter plasma concentrations of pituitary hormones important to cattle production.

Animals↗
PubMed2002

Endocrine and respiratory responses to ergotamine in Brahman and Hereford steers.

Ergot alkaloids are considered causative agents of fescue toxicosis, a syndrome experienced by cattle consuming tall fescue (Festuca arundinacea) infected with the fungal endophyte Neotyphodium coenophialum. One sign of fescue toxicosis in cattle is severe hyperthermia. This study assessed hormonal responses to ergotamine in heat-sensitive and heat-tolerant cattle. Seven Hereford (heat-sensitive, Bos taurus) and 7 Brahman (heat-tolerant, Bos indicus) steers on a fescue-free diet received ergotamine tartrate iv. Blood was sampled every 15 min for 2 h before and 4 h after dosing for determination of circulating hormonal changes. Respiration rates were recorded hourly. Ambient temperature and relative humidity averaged 31C and 48%, respectively, during sampling. A breed x time interaction existed (p < 0.01) for plasma prolactin, LH, insulin, glucagon, cortisol, triiodothyronine and glucose concentrations. The breed x time interaction tended to affect (p = 0.14) growth hormone and influenced (p < 0.01) respiration rates. Ergotamine reduced (p < 0.01) plasma LH and increased (p < 0.01) growth hormone concentrations in Brahman. Both breeds responded to ergotamine with increased (p < 0.01) plasma cortisol, glucagon, and glucose and reduced (p < 0.01) insulin concentrations. The magnitude of response for cortisol, insulin, and glucose were greater for the Brahman. Ergotamine increased (p < 0.01) plasma triiodothyronine and respiration rates in Hereford, whereas these traits were unaltered in Brahman. Acute ergotamine exposure generally resulted in similar effects on Brahman and Hereford steers. The triiodothyronine and respiratory comparisons revealed modified responses in Brahman that suggest a potential benefit of using heat-tolerant genetics to reduce the adverse effects of fescue toxicosis in cattle.

Animals↗
PubMed1981

Effects of ergotamine on isolated human vessels.

In isolated human mesenteric and crural veins, ergotamine induced long-lasting contractions. These contractions were resistant to repeated wash-out and were not affected by alpha-adrenoceptor blockade, but could be abolished by removal of extracellular calcium or by the presence of the calcium-blocker nifedipine. In contrast to its effect on human mesenteric and crural veins, ergotamine had no contractile effect, but a marked relaxant effect on mesenteric arteries mediated via blockade of alpha-receptors. The ergotamine-induced contraction was not affected by indomethacin (0.28--2.8 microM) nor was it influenced by serotonin (5-HT). In both mesenteric and crural veins, the ergotamine-induced contraction was diminished by the 5-HT blocking agent, methysergide. In veins, development of tachyphylaxis to 5-HT was demonstrated. It is concluded that ergotamine has a direct contractile effect on isolated human mesenteric and crural veins. These effects are dependent on unhindered influx of extracellular calcium and are at least partly mediated via 5-HT receptors. In mesenteric arteries, ergotamine acted as an alpha-adrenoceptor blocker, and had no contractant effect.

Adult↗
PubMedDate not supplied

The antimigraine effect of ergotamine: a role for alpha-adrenergic blockade?

The hypothesis that alpha-adrenergic receptor blockade accounts for the ability of ergotamine to stop migraine attacks was tested, in migraine patients, in an experimental migraine model based on nitroderivative- induced attacks. In a preliminary single blind, placebo controlled study, thymoxamine, a prevalently post-synaptic alpha adrenergic receptor antagonist, was able to abort migraine attack in 9 out of 10 patients, as opposed to 2 out of 10 by placebo (p < 0.005 Fisher's exact test). In a subsequent randomized, crossover, placebo controlled double blind study, the ability of a selective alpha-1 adrenergic receptor agonist, methoxamine, to block ergotamine antimigraine effect was studied. In 26 patients migraine was induced in two separate tests and then ergotamine was administered once after methoxamine pretreatment and once after placebo; methoxamine was significantly more effective than placebo in blocking antimigraine effect of ergotamine (p = 0.0055 Fisher's exact test). These results support the hypothesis that ergotamine alpha-1 adrenolytic properties may account for its antimigraine effect suggesting that this action takes place outside the blood-brain barrier, since methoxamine can cross it very poorly. Ergotamine target structure could be the trigeminal innervation of the extracranial and/or dural vessels.

Adolescent↗