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At least 19 recordsLinked to original sources
PubMed1975

Analysis of ergotamine - 5-HT interaction on the isolated rat stomach preparation.

The effect of ergotamine on the isolated rat stomach and its influence on the response to ACh and 5-HT were investigated. The log dose-response curve of ergotamine was bell-shaped. Extension of the incubation time of ergotamine resulted in a parallel shift to the left of the curve. The response to ergotamine was inhibited by methyserigide and piperoxan. Incubation with ergotamine resulted in a decrease of the pD2-value of 5-HT together with a marked suppression of the maximum of the 5-HT curve. The response to ACh was affected in accordance with the prediction of an action of ACh and ergotamine on different receptors. The prolonged receptor stimulation by 5-HT or ACh resulted in a decrease of the apparent affinity towards their receptors. Incubation with ACh resulted in a parallel shift to the right of the 5-HT curve. However no inconsistency with the theoretical prediction of an action on separate receptors was observed with the ACh curve in the presence of 5-HT. It is concluded that ergotamine is a partial agonist on the D-tryptamine receptors of tbe isolated rat stomach. The marked decrease of the maximum of the 5-HT curve by ergotamine is probably caused by the slowly reversible character of its antagonism. The parallel shift to the left of the ergotamine curve with the extension of the incubation time and the persistence of its antagonism both are probably caused by a slow diffusion into and from the biophase.

Acetylcholine↗
PubMed1989

Reduced serotonin vascular sensitivity in ergotamine abusers.

The action of ergotamine on the 5-hydroxytryptamine (5-HT) venous sensitivity was studied in ergotamine abuser and non-abuser migraine patients. Ergotamine abusers showed reduced 5-HT hand vein contraction during abuse, compared to seven days after ergotamine withdrawal. In non-ergotamine users, the 5-HT venoconstriction was not significantly modified 12 h after a single intramuscular ergotamine (0.25 mg) administration. Even the administration of ergotamine locally into the vein did not change the venospasm of 5-HT given acutely in the same vein. Therefore, it seems that the 5-HT antagonism does not contribute to the therapeutic effect of ergotamine during the migraine attack. Moreover, the reduced 5-HT responsiveness during ergotamine abuse may possibly be compatible with the chronic headache present in some abusers, the withdrawal headache attacks and the abuse itself.

Adult↗
PubMed1990

Pressor effect of inhaled ergotamine in orthostatic hypotension.

Treatment of orthostatic hypotension due to autonomic failure frequently necessitates use of pressor agents. Because venous pooling contributes significantly to this disorder, the venoconstrictive properties of ergotamine offer theoretical advantages over pure arteriolar pressor agents. However, the low and erratic bioavailability of oral preparations has hindered the use of ergotamine. Accordingly, the efficacy of inhaled ergotamine tartrate (1 puff, 0.36 mg) was compared to placebo in 8 patients with severe autonomic failure. Blood pressure was monitored in the seated position with an automated device. Ergotamine produced significant increases in systolic (29 +/- 5 mm Hg, p less than 0.01 by analysis of variance) and diastolic (13 +/- 1 mm Hg, p less than 0.001) blood pressures compared to placebo (-9 +/- 5 and -2 +/- 3, respectively). Upright blood pressure 2 hours after administration was significantly greater with ergotamine (119 +/- 8/69 +/- 6 mm Hg) vs placebo (82 +/- 7/59 +/- 5 mm Hg, p less than 0.05). Motionless standing time, a measurement of functional capacity, also improved with ergotamine (200 +/- 58 vs 85 +/- 22 seconds). No side effects were noted, but patients with coronary or peripheral artery disease were excluded. Inhaled ergotamine may provide an effective and practical therapy for disabling orthostatic hypotension due to autonomic failure.

Administration, Inhalation↗
PubMed1992

Comparative effects of the antimigraine drugs sumatriptan and ergotamine on the distribution of cardiac output in anaesthetized pigs.

The haemodynamic effects of sumatriptan, a 5-HT1-like receptor agonist, and ergotamine, an agonist at alpha-adrenergic, dopamine as well as 5-HT receptors, were compared using intracardiac injection of radioactive microspheres of different sizes in anaesthetized pigs. Ergotamine (0.02 mg.kg-1) and sumatriptan (0.3 mg.kg-1) decreased systemic vascular conductance and cardiac output. Only ergotamine raised arterial blood pressure. Both sumatriptan and ergotamine decreased arteriovenous anastomotic, but not capillary, blood flow in the head and body skin. Arteriovenous and capillary blood flow in the dura mater and nasal mucosa and capillary blood flow in the brain, kidneys, adrenals, intestine, heart, spleen and muscle remained unchanged. However, kidney conductance was decreased by both drugs, spleen conductance by sumatriptan and heart, liver and adrenal conductances were decreased by ergotamine. Thus, both sumatriptan and ergotamine constricted arteriovenous anastomoses in the skin, but not in the dura mater or nasal mucosa. Ergotamine constricted the vasculature more than sumatriptan, although both drugs may differentially decrease vascular conductances in some organs.

Anesthesia↗
PubMed1978

The effect of ergotamine on tissue blood flow and the arteriovenous shunting of radioactive microspheres in the head.

1 The radioactive microsphere method was used to study the effects of ergotamine (5, 10 and 20 mug/kg, i.v.) on systemic and regional haemodynamic variables in chloralose-urethane anaesthetized cats. The influence of the drug was also studied on the number of 15 mum microspheres escaping entrapment in the head to emerge in the left external jugular vein.2 Ergotamine decreased the heart rate and cardiac output. Since arterial blood pressure remained unchanged, calculated total peripheral resistance increased.3 The regional distribution of cardiac output obtained with 15 mum microspheres agreed well with previous studies in cats where 25 mum spheres were used. The most pronounced difference was that in the present investigation more microspheres, apparently escaping through arteriovenous anastomoses (AVAs), were detected in the lungs than when larger spheres had been used.4 Coronary blood flow decreased, while uterine blood flow was increased by the drug. The microsphere content of the lungs, which receive the spheres not only via bronchial arteries but also via AVAs, was greatly reduced by all doses of ergotamine. Ergotamine did not influence tissue blood flow to other major organs such as the brain, kidneys, skin, liver, skeletal muscle or the gastrointestinal tract.5 In the 16 experiments, 0.46 +/- 0.05 (s.e. mean)% of the total microspheres injected (equivalent to 11.7 +/- 1.4% of microspheres detected in the left-side of the head) appeared within 2 min of microsphere injection into the left external jugular vein. The highest dose of ergotamine significantly reduced the shunting of the microspheres in the head.6 Since 15 mum microspheres are only likely to reach the lungs by passing into the venous circulation through large glomus-type AVAs, we conclude that ergotamine reduces the fraction of microspheres appearing in the lungs by causing strong vasoconstriction in the AVAs in the head.7 In conformity with the closure of head AVAs is the finding that ergotamine reduced the jugular venous Po(2) and O(2) saturation thereby increasing the A-V O(2) saturation difference.8 It is quite possible that decreased A-V shunting may be the prominent mechanism of the antimigraine action of the drug, since sudden opening of AVA's has been implicated in the pathophysiology of migraine-syndrome.

Animals↗
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↗
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↗
PubMed1991

Ergotamine, flunarizine and sumatriptan do not change cerebral blood flow velocity in normal subjects and migraneurs.

Changes in the diameter of extracranial and intracranial arteries resulting in changes in cerebral blood flow have previously been assumed to be the most important pathophysiological factor in migraine. To test this hypothesis 20 normal subjects, and three groups of patients (n = 29) with migraine were investigated by means of transcranial Doppler sonography. Blood flow velocities in the middle cerebral (MCA) and in basilar (BA) arteries were measured. Data from patients were obtained in the interval between migraine attacks, during migraine attacks and following treatment with either ergotamine (0.5 mg i.m.; n = 10); flunarizine, a calcium overload blocker (20 mg i.v.; n = 13); or a 5-HT1-like agonist (sumatriptan, 4 mg s.c.; n = 6). Ergotamine and sumatriptan are constrictors of cerebral arteries in animal experiments. The arithmetic mean of flow velocity in the BA was reduced in normal subjects (45 cm/s) as compared with patients with migraine measured in between attacks (53 cm/s). Mean flow velocity in MCA was not different in normals (72.5 cm/s) as compared with migraineurs (75 cm/s). Neither ergotamine nor the 5-HT1 agonist and flunarizine resulted in a significant change in blood flow velocity in MCA and BA. This was true irrespective of whether the drugs were given in the headache-free period, during a migraine attack or during the withdrawal phase of drug-induced headache. Ergotamine was effective in improving headache during migraine attacks and sumatriptan attenuated headache during drug withdrawal from chronic analgesic intake. These results indicate that the action of ergotamine and the 5-HT1-receptor agonist is probably not mediated by their vasoconstrictor action on cerebral arteries.

Adult↗
PubMed1979

Systemic availability of ergotamine tartrate after oral, rectal and intramuscular administration.

Plasma ergotamine levels were measured in 33 volunteers (subgroups 11, 12 and 10) after a single dose of ergotamine administered by various routes. Ergotamine tartrate was given in doses normally used in the treatment of acute migraine--2.0 mg orally, 2.0 mg combined with 100 mg caffeine rectally and 0.5 mg i.m. Plasma ergotamine concentrations were determined by radioimmunoassay. The highest and longest lasting levels were found after i.m. administration, the peak concentration being 1.94 +/- 0.34 (SEM) ng/ml at 1/2 h. The corresponding maximum concentrations after oral and rectal administration were 0.36 +/- 0.08 ng/ml at 2 h and 0.42 +/- 0.09 ng/ml at 1 h. In most of the subjects the plasma ergotamine level began to rise again at 24 to 48 h. The cause of the elevation is not known but it might favour possible accumulation of the drug. Absorption from suppositories was at least as good as after oral administration and the former route may therefore be advantageous for migraine patients in whom nausea and vomiting during an attack may prevent efficient oral medication.

Administration, Oral↗
PubMed1979

Presynaptic inhibition by ergotamine of the responses to cardioaccelerator nerve stimulations in the cat.

The effects of ergotamine on the tachycardia elicited by postganglionic stimulation of the cardioaccelerator nerve have been investigated in both intact and spinal (desmethylimipramine-pretreated) cats. Ergotamine (2.5--20 microgram kg-1) selectively antagonized the response to low-frequency (0.3--3 Hz) stimulation. The responses elicited by stimulation of the nerve with higher frequencies (greater than 10 Hz) either remained unaltered or were facilitatated by the drug. Pretreatment of the cats with pimozide (0.2 mg kg-1) completely antagonized the inhibitory effects of ergotamine on the sympathetic neuron. Although phentolamine (0.5 mg kg-1) did appear to attenuate the effects of ergotamine, the changes were, however, not statistically significant. Since the drug did not reduce the cardiac effects of isoprenaline or tyramine, it is concluded that ergotamine interferes with the release of noradrenaline from the cardioaccelerator nerve, mainly by stimulating the presynaptic dopaminergic receptors. This effect may be an important mechanism by which the drug causes bradycardia in almost all species regardless of the blood pressure response.

Animals↗
PubMed1992

Is dietary ergotamine atherogenic in the rabbit?

The effect of dietary ergotamine on pre-lesional indicators of atherosclerosis was studied in rabbits. The experimental purified diets contained 0.08% (w/w) cholesterol and either 0, 40 or 200 mg ergotamine-tartrate/kg. After 6 wk, serum total cholesterol concentration and the ratio of serum total cholesterol: high-density lipoprotein-cholesterol were significantly increased by ergotamine in a dose-dependent manner. Dietary ergotamine raised the total level of glycosaminoglycans and the relative proportion of chondroitin sulphate in the abdominal aorta. It is suggested that dietary ergotamine is atherogenic in the rabbit.

Animals↗
PubMed1976

Quantitative thin-layer chromatographic analysis of ergotamine tartrate and caffeine in the nanogram range.

Direct, quantitative, thin-layer chromatographic methods for the determination of ergotamine tartrate and caffeine in the presence of each other in blood and in pharmaceutical preparations are described. The blood is centrifuged, the plasma decanted from the coagulum and deproteinized with acetone-methanol. After removal of the solvent mixture, the active ingredients are extracted from the remaining aqueous solution with chloroform. In the case of the pharmaceutical preparations, the active ingredients are also extracted with chloroform or methanol. Ergotamine tartrate and caffeine are separated on pre-coated silica gel 60 F254 plates and measured directly on the thin-layer plate, ergotamine tartrate being determined by the fluorescence method, excitation wavelength 365 nm, at lambdamax.=450 nm and caffeine by the reflactance method at lambdamax.=274 nm. The analytical methods are suitable for the bioavailability studies of these drugs in blood as they enable the determination of 20 ng ergotamine tartrate with a coefficient of variation of 6.7% and the determination of 200 ng caffeine with a coefficient of variation of 6.1%. The methods have also proved useful in the determination of the active ingredients of drug forms such as tablets and suppositories and can be well reproduced with a maximum coefficient of variation of 4.9% for ergotamine tartrate and 3.5% for caffeine.

Biological Availability↗
PubMedDate not supplied

Regional myocardial perfusion and wall thickness and arteriovenous shunting after ergotamine administration to pigs with a fixed coronary stenosis.

The hemodynamic effects of antimigraine drug ergotamine, which is considered contraindicated in patients with coronary artery disease, were studied in pigs with a normal myocardial circulation (doses of 8, 16, and 32 micrograms/kg, i.v.) or with acute coronary stenosis (8 micrograms/kg). In both groups of animals, ergotamine decreased heart rate, cardiac output, and arteriovenous anastomotic blood flow while increasing aortic blood pressure and systemic vascular resistance. No effects on total ventricular blood flow and its distribution within the myocardium were found in normal animals. In animals with a clamp on the left anterior descending coronary artery (LAD), the blood flow to the LAD-perfused area was reduced from 1.10 +/- 0.16 to 0.67 +/- 0.05 cm3/min/g. The endocardium was affected more than the epicardium and the endo/epi flow ratio decreased from 1.18 +/- 0.05 to 0.74 +/- 0.07. Ergotamine increased the blood flow to the ischemic zone towards normal values, and the endo/epi flow ratio to 1.05 +/- 0.21. However, myocardial wall thickness parameters, which showed functional deterioration during ischemia, did not change after ergotamine. The present study provides no clear support for cardiovascular contraindications to ergotamine administration.

Animals↗
PubMed1992

Ketoprofen and ergotamine in acute migraine.

The objectives of this study were to evaluate and compare the efficacy and tolerability of ketoprofen and ergotamine in the treatment of acute migraine attacks without aura. The study design was a single-centre, double-blind, placebo-controlled, cross-over comparison of a single dose of ketoprofen (100 mg) and ergotamine (2 mg) suppositories in the treatment of acute migraine attacks. Fifty patients were included in the statistical evaluation. Ketoprofen was found to be more efficient than ergotamine and placebo in reducing the severity of pain. Ketoprofen was found to be more satisfactory than ergotamine and placebo with regard to influence on working ability, and better than placebo in global assessment. We conclude that ketoprofen (100 mg suppository) is superior to ergotamine (2 mg suppository) and placebo in the symptomatic treatment of acute migraine attacks, and has better tolerability.

Acute Disease↗
PubMed1991

The antimigraine drugs ergotamine and dihydroergotamine are potent 5-HT1C receptor agonists in piglet choroid plexus.

1. Fozard & Gray (1989) proposed that migraine is mediated by stimulation of 5-HT1C receptors. We have examined the interaction of two effective anti-migraine agents, ergotamine and dihydroergotamine (DHE), with these receptors. Binding (inhibition of labelling by [3H]-mesulergine) and agonist activity (phosphoinositide hydrolysis) were measured in piglet choroid plexus, a tissue rich in 5-HT1C receptors. 2. The pKD for [3H]-mesulergine binding was 8.4. Ergotamine and DHE both inhibited [3H]-mesulergine binding with a pKD of 7.1. This was similar to the potency of m-chlorophenylpiperazine (m-CPP) (pKD 7.4) and rather less than that of 5-hydroxytryptamine (5-HT) (pKD 8.1). 3. Both ergotamine and DHE were full agonists (pEC50S 7.5 and 7.6 respectively) with potencies similar to that of 5-HT (pEC50 7.7) and greater than that of m-CPP (pEC50 7.1). Mesulergine 10(-7) M produced near-parallel rightward shifts of the concentration-response curves for all these agents of 1.8-2.2 log units, consistent with an action of the agonists at the same receptor. 4. There was no effect of prazosin, spiperone, mepyramine or atropine on the phosphoinositide hydrolysis induced by ergotamine, ruling out an action via alpha 1-adrenoceptors, 5-HT2, histamine H1, or muscarinic receptors. 5. It is concluded that, together with 5-HT, ergotamine and DHE are the most potent 5-HT1C agonists reported so far. These findings do not support the theory that 5-HT1C receptor activation causes migraine.

Animals↗
PubMed1991

[Headache caused by analgesic and/or ergotamine abuse].

Headache induced by ergotamine-abuse was described 40 years ago. More recently there is ample evidence suggesting that chronic headache may also be provoked by analgesic abuse. A recent Classification of the International Headache Society has defined this kind of headache as an autonomous disease. It consists in a daily chronic headache with paroxysmal attacks associated with daily or almost daily assumption of analgesics and/or ergotamine. It is debated whether the term "abuse" or "dependence" is correct. Almost 5% of patients of the Headache Centres in Italy were found to be drug abusers. Most of these patients originally suffered from migraine. The therapeutic approach consists in hospitalization, withdrawal of analgesics and/or ergotamine, treatment of the withdrawal headache (which appears within 48 hours and lasts even 1-2 weeks) and finally in a prophylactic therapy. Although several treatments have been suggested for the abstinence syndrome, only fluid replacement, antiemetics, hypnotic-sedative drugs and rarely mild analgesics are necessary. A review of the literature shows the following success rates in the relief of the headache: above 50% relief in more than 60% of patients within a follow up period of 1 to 3.5 years as mean. Even if caffeine and barbiturates, which are often contained in the analgesic and ergotamine preparations, might be considered the cause of the abuse and withdrawal syndrome, they don't seem to play a fundamental role in this syndrome. An impairment of the central antinociceptive system was hypothesized to be involved in the pathogenesis of the headache associated with analgesic and/or ergotamine abuse. Recently there has been evidence of a possible hyposensitivity of the adrenergic and serotoninergic receptors of the central nervous system. It is still to be proved whether drug abuse is the cause or the consequence of the headache chronicization. The remarkable improvement of headache after analgesic withdrawal suggests a causal factor.

Analgesics↗
PubMed1976

Evidence for stimulation of 5-HT receptors in canine saphenous arteries by ergotamine.

Changes in tension of spiral strips from dog saphenous arteries were monitored isometrically. Dose-response curves for noradrenaline, 5-HT and ergotamine were established without and after a 30 min incubation with phentolamine or pizotifen. Phentolamine was about 15 times more potent in antagonizing responses to noradrenaline (pA2 value=7.4) than those to 5-HT (pA2 value=6.2) but it was nearly equipotent in antagonizing responses to ergotamine (pA2 value=6.5) and those to 5-HT. Pizotifen was about 500 times less potent in antagonizing noradrenaline effects than 5-HT but again nearly equipotent when tested against ergotamine and 5-HT. It is suggested that in canine saphenous arteries the stimulant activity of ergotamine is mediated mainly through 5-HT receptors.

Animals↗