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PubMed1976

The role of free serum tryptophan in the biphasic effect of acute ethanol administration on the concentrations of rat brain tryptophan, 5-hydroxytryptamine and 5-hydroxyindol-3-ylacetic acid.

1. Acute administration of ethanol exerts a biphasic effect on the concentrations of rat brain tryptophan, 5-hydroxytryptamine and 5-hydroxyindol-3-ylacetic acid. Both effects are associated with corresponding changes in the availability of circulating free tryptophan. 2. The initial increases in the above concentrations are prevented by ergotamine, are unaltered by allopurinol and are potentiated by theophylline, whereas the later decreases are prevented by both ergotamine and allopurinol. 3. It is suggested that the initial enhancement by ethanol of brain tryptophan metabolism is caused by catecholamine-mediated lipolysis followed by displacement of protein-bound serum tryptophan, whereas the activation of liver tryptophaan pyrrolase, which is produced by the same mechanism, leads to the later decreases in the brain concentrations of tryptophan and its metabolites. 4. The initial effects of ethanol can be reproduced by an equicaloric dose of sucrose, and a comparison of the two treatments alone could therefore be misleading. 5. The effects of ethanol on liver and brain tryptophan metabolism have also been examined in mice, and a comparison of the results with those previously reported suggests that the ethanol effects are strain-dependent.

Allopurinol↗

PubMed1996

Long-term outcome of patients with headache and drug abuse after inpatient withdrawal: five-year follow-up.

Thirty-eight patients with "chronic daily" headache and ergotamine and/or analgesics abuse according to the criteria proposed by the International Headache Society were re-investigated 5 years after inpatient drug withdrawal. At the end of the observation period, 19 patients (50.0%) had their headaches on only 8 days per month or less, 18 patients (47.4%) were free of symptoms or had only mild headaches. A close correlation was found between the frequency of headache and the duration of drug abuse, as well as between the intensity of headache and the number of tablets taken per month. Frequency and intensity of headache had changed within the first 2 years after withdrawal, but remained stable afterwards. Fifteen patients (39.5%) reported on recurrent drug abuse. Patients with migraine showed a tendency towards a better prognosis compared to patients with tension-type headache or with combined migraine and tension-type headache. The results of this study highlight the long-term efficacy of inpatient drug withdrawal in patients with headache and ergotamine and/or analgesics abuse.

Adult↗

PubMed1996

Characterisation of human 5-hydroxytryptamine2A and 5-hydroxytryptamine2C receptors expressed in the human neuroblastoma cell line SH-SY5Y: comparative stimulation by hallucinogenic drugs.

Stable transfection of the human neuroblastoma cell line SH-SY5Y with the human 5-hydroxytryptamine2A (5-HT2A) or 5-HT2C receptor cDNA produced cell lines demonstrating ligand affinities that correlated closely with those for the corresponding endogenous receptors in human frontal cortex and choroid plexus, respectively. Stimulation of the recombinant receptors by 5-HT induced phosphoinositide hydrolysis with higher potency but lower efficacy at the 5-HT2C receptor (pEC50 = 7.80 +/- 0.06) compared with the 5-HT2A receptor (pEC50 = 7.30 +/- 0.08). Activation of the 5-HT2A receptor caused a transient fourfold increase in intracellular Ca2+ concentration. Whole-cell recordings of cells clamped at -50 mV demonstrated a small inward current (2 pA) in response to 10 microM 5-HT for both receptors. There were no differences in potency or efficacy of phosphoinositide hydrolysis among four hallucinogenic [d-lysergic acid diethylamide (LSD), 1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane (DOI), 5-methoxy-N,N-dimethyltryptamine, and mescaline] and three nonhallucinogenic drugs (m-chlorophenylpiperazine, quipazine, and ergotamine). Comparison of equipotent doses producing 20% of the maximal response induced by 5-HT revealed selective activation of the 5-HT2A receptor by LSD and to a lesser degree by DOI, mescaline, and ergotamine. Quipazine and 5-methoxy-N,N-dimethyltryptamine were relatively nonselective, whereas m-chlorophenylpiperazine selectively activated the 5-HT2C receptor. It is unlikely therefore that hallucinosis is mediated primarily by activity at the 5-HT2C receptor, whereas activity at the 5-HT2A receptor may represent an important but not unique mechanism associated with hallucinogenic drug action.

Adrenergic alpha-Agonists↗

PubMedDate not supplied

Effect of withdrawal of misused medication on sleep disturbances in migraine sufferers with chronic daily headache.

OBJECTIVES: To evaluate the sleep pattern of migraineurs with chronic daily headache and to determine whether and to what degree it is improved by withdrawal of medication, and to reconfirm relief of headache by withdrawal of medications in migraineurs with chronic daily headache due to medication misuse. BACKGROUND: Misuse of ergotamine and analgesics by migraineurs is one of the causes of chronic daily headache. The latter is alleviated or abolished in these patients by abrupt withdrawal of the misused medication. In common with patients with chronic daily headache, migraineurs frequently complain of insomnia, usually verifiable by polysomnography. METHODS: Twenty-six women with migraine, aged 18 to 49 years, with chronic daily headache due to medication misuse, voluntarily discontinued ergotamine and analgesics, and were followed at monthly intervals for 3 months. In 25 subjects, polysomnography was performed before withdrawal of medication and 3 months after withdrawal. All subjects filled out a standard sleep questionnaire on those two occasions and a daily self-assessment questionnaire focused on headaches. RESULTS: After 3 months, a significant decrease in mean headache frequency (P<.001) and intensity (P<.001) was demonstrated. Polysomnography performed 3 months after medication withdrawal showed significant improvement in total sleep time (P<.05), sleep efficiency (P<.05), and number of arousals (P<.001). The score of the sleep questionnaire was also significantly improved (P<.01). CONCLUSIONS: In migraineurs with chronic daily headache due to medication misuse, withdrawal of the misused medications alleviates the associated sleep disturbance along with diminution in frequency and intensity of chronic daily headache.

Adult↗

PubMed1992

[Drug-induced headache].

Migraine or tension-type headache lasting for several years is frequently complicated by chronic daily headaches. Those patients recurrently take analgesics or ergotamines. Headache induced by chronic ergotamine use is well known. Recent studies, however, have shown that a similar form of headache is caused by analgesic abuse. Treatment of drug-induced headaches envisages withdrawal of the headache medication.

Analgesics↗

PubMed1994

[Acute ischemia of an arm as an unusual manifestation of ergotism].

A 27-year-old woman developed acute pain, pallor and feeling of cold in her left arm. She had been a smoker of 15-20 cigarettes daily since the age of 15 years, but had not previously had any serious illness. In addition to contraceptives she had had been taking one to several suppositories containing caffeine and ergotamine tartrate (2 mg) daily against migraine. Angiological examination 5 days after onset of symptoms discovered a weak brachial pulse low in the left upper arm, while ulnar and radial pulses were absent. All other pulses were normally palpable. Colour duplex sonography demonstrated occlusion of the brachial artery which angiographically was due to a 5 cm severe narrowing without thrombus, blood flowing distally via collaterals. No improvement was achieved by local injection of 100,000 IU urokinase, 0.5 mg nitroglycerin, 20 mg tolazoline and a 3-hour infusion of alprostadil. On infusion of 560 ml hydroxyethylstarch over 8 hours, 400 mg naftidrofuryl, therapeutic doses of heparin and abstinence from ergotamine (since admission) the vessel diameter increased by 50% within 23 hours and after a further 24 hours to almost 100% of the comparable arterial segment of the right arm while merely on heparin infusion.

Acute Disease↗

PubMed1991

[Extremity-threatening ischemia in ergotism. Successful treatment with the intra-arterial administration of nifedipine].

A 39-year-old woman suffering from migraine took two suppositories of an ergotamine-containing proprietary drug (Cafergot, containing 2 mg ergotamine tartrate) for the first time again after an abstinence of two years. Twenty-four hours later she developed symptoms of decreased peripheral blood flow in all four limbs. Walking distance without pain was reduced to 100 m, but the severest changes affected the right arm, with livid discolorations and complete immobility 16 hours after the onset of symptoms. Despite administration of morphine derivatives the pain progressively increased. Angiography demonstrated spastic narrowing of all arm arteries below the axillary artery. No vessels were visualized below the lower-arm bifurcation. Thereupon 4 mg nifedipine were injected through the angio-catheter within 30 min (five individual doses of 0.8 mg each). This was followed by intravenous infusion of 0.5 mg/h. The pain immediately decreased and the livid discoloration as well as impaired arm movement improved. A residual deficit, incomplete lesion of the median nerve, persisted but gradually regressed during the following two months.

Acute Disease↗

PubMed2003

Incidence and determinants of antidepressant drug use in migraine patients.

The purpose of this retrospective, follow-up study was to characterise the use of antidepressant medication in a defined migraine population and evaluate the determinants thereof. Data was obtained from the PHARMO-RLS prescription database. Our migraine population (2,517 people) included patients having commenced specific migraine drugs, ergotamine or sumatriptan, for the first time from January 1 1992 to December 31 1998. The corresponding date was termed the 'index date'. Non-migraine patients, those not having used any medication specific for migraine, were selected and equally matched (n=2,517). The cumulative incidence of initiating antidepressant treatment was estimated during two-year observation periods prior to and after the index date. Several demographic and comedication characteristics were assessed as potential determinants of antidepressant drug use within the migraine population. Other determinants included usage patterns ("therapeutic intensity") of ergotamine and sumatriptan, defined as the absolute number of Defined Daily Doses (DDDs) dispensed per patient during one year prior to initiation of antidepressant therapy. A total of 300 migraine patients (11.9%) and 213 non-migraine patients (8.5%) had initiated antidepressant treatment in the two-year period prior to or in the two-year period after the index date (RR adj 1.4; 95% CI 1.2-1.7). The cumulative incidence of initiation of antidepressant treatment for the migraine population was 3.0% per year prior to and 3.2% per year after the initiation of specific migraine analgesia. The concomitant use of benzodiazepines (RR adj 4.7; 95% CI 3.5-6.3), migraine prophylactic medication (RR adj 2.1; 95% CI 1.6-2.8) and heavy therapeutic intensity use of specific migraine analgesia, defined as >/=150 DDDs per year were highly predictive of antidepressant drug use within the migraine population. In conclusion, compared to the non-migraine population, the initiation of antidepressant treatment was only slightly higher in the migraine population. A number of determinants within the latter were found to be strongly associated with antidepressant drug use, the nature of which most likely reflects an increased severity of migraine whereby therapeutic needs are higher.

Adult↗

PubMed2006

Oligosaccharides in colostrum of Italian and Burkinabe women.

Human milk contains a large number of compounds to provide nutrition and defense for the newborn. Among these, oligosaccharides are present in concentrations up to 12 g/L, and their composition varies during lactation. Colostrum from 53 Burkinabe women were collected at the maternity department of St Camille Medical Centre in Ouagadougou (Burkina Faso, West Africa). Colostrum from 50 Italian women were collected at the maternity department of St Bambino Hospital in Catania (Catania, East Sicily, Italy). All mothers spontaneously delivered at term. Italian mothers received an injection of the ergot derivative ergotamine after delivery. Ergotamine, notoriously, delays breastfeeding initiation up to 2 to 3 days. Chromatographic separation of colostrum from both Burkinabe and Italian women showed a progressive appearance of oligosaccharides in the first 3 days. Burkinabe women showed high concentrations of 2-fucosyllactose and lower concentrations of lacto-N-fucopentaose I. By contrast, Italian women showed inverted behaviour. A comparable percentage of the secretor genotype for the Lewis blood group phenotype in both Burkinabe and Italian women was found. According to the different ethnicity, different milk oligosaccharide profiles were documented in the present study. 2-Fucosyllactose in milk should be biologically significant for Burkinabe infants because of the high levels found in their mothers' colostrum after the second day of lactation.

Burkina Faso↗

PubMed1980

Peripheral blood flow in chronic ergotism.

Muscle blood flow (MBF) was determined in 11 patients on chronic overdoses of ergotamine tartrate and in 12 controls, using the local 133xenon clearance method. The difference in MBFs between the groups was insignificant, 59.7 +/- 21.4 and 61.6 +/- 10.8 ml/100 g/min, respectively. Six patients taking ergotamine in doses exceeding 0.25 mg/kg/week showed a significant (p less than 0.01) reduction of MBF (45.2 +/- 10.7 ml/100 g/min). This reduction could be measured before the manifestation of symptoms or signs of circulatory insufficiency.

Adult↗

PubMed1971

Effects of adrenoceptor blocking agents on body temperature.

1. The effect on rectal temperature of adrenoceptor blocking agents, injected through a cannula chronically implanted into a lateral cerebral ventricle, was examined in unanaesthetized rabbits, cats and rats, kept at room temperature (19-22 degrees C).2. In rabbits, the alpha-adrenoceptor blocking agent phenoxybenzamine (50 or 100 mug) produced marked hypothermia when injected intraventricularly but not when injected intravenously. In some rabbits as little as 1 mug was effective on intraventricular injection. Phentolamine and ergotamine, the other alpha-adrenoceptor blocking agents examined, had a much weaker hypothermic action when injected intraventricularly, whereas the beta-adrenoceptor blocking agents propranolol, pronethalol and Trasicor had no effect.3. In rabbits in which the noradrenaline stores of the hypothalamus were depleted by intraventricular injections of reserpine, the hypothermic effect of phenoxybenzamine was abolished and remained abolished for a few days.4. In cats, an intraventricular injection of phenoxybenzamine (200 mug) produced long-lasting hyperthermia, but not in all cats, and only with the first, or the first two or three injections. Injected intraperitoneally, this dose had no effect on temperature. Phentolamine (100 or 200 mug) had a very weak hyperthermic effect and phentolamine (500 mug), a hypothermic effect, but only on intraventricular injection, whereas ergotamine (100 and 200 mug) had a weak hyperthermic effect both on intraventricular and intraperitoneal injection. Propranolol and Trasicor had no effect on temperature when injected intraventricularly.5. In rats, phenoxybenzamine (5 or 20 mug) produced long-lasting hypothermia on intraventricular injection.6. Some of the temperature effects produced by intraventricular injections of the alpha-adrenoceptor blocking agents are explained on the assumption that they prevent the effect on temperature produced by a continuous release of noradrenaline from adrenergic neurones innervating the anterior hypothalamus.

Amino Alcohols↗

PubMedDate not supplied

Application of metoclopramide specificity in migraine attacks therapy.

The 5-HT3 antagonism property of metoclopramide, acting on receptors presumably located in the trigeminovascular system, is the theoretical basis of its remarkable success, as a single intravenous agent, in the treatment of migraine attacks. The specific anti-migraine activity of oral metoclopramide is, most probably, applicable only when its plasma level is equivalent to 10 mg injected intravenously. The clinical effective dose of ergotamine, beginning from the minimal dose of 1 mg, correlates well with its affinity for 5-HT1B and 5-HT1D receptors, and the rank order of clinical potency of ergotamine is superior to sumatriptan. The presumed synergic power of drugs that interact with both 5-HT1 and 5-HT3 receptors is examined, in order to formulate a highly potent, low headache recurrence, oral combination.

Caffeine↗

PubMed1975

Changes in cerebral blood flow during a migraine attack.

Regional cerebral blood flow studies during a typical prodromal phase of a migraine attack in a young woman showed a global decrease of cerebral blood flow in the carotid artery territory. These studies were repeated during the subsequent headache phase of the same attack and hemispheric blood flow increased considerably. Ergotamine tartrate was then administered intramuscularly which brought definite relief of symptoms but no change in cerebral blood flow. Carotid angiography performed immediately afterwards showed retrograde filling of the proximal portion of the basilar artery, which suggested that the brain stem was the site of hyper-perfusion. These findings illustrate certain features underlying both the pathophysiology of migraine itself and its response to ergotamine preparations.

Adolescent↗

PubMed1975

Positive inotropic effects of methoxamine: evidence for alpha-adrenergic receptors in ventricular myocardium.

The present study was undertaken to evaluate the effects of methoxamine on force development and adenyl cyclase activity in cat ventricular myocardium. Methoxamine produced a dose-related increase in force development of isometrically contracting cat papillary muscles. The positive inotropic effects of methoxamine were not altered by beta-adrenergic blockade (propranolol), or catecholamine depletion by prior reserpinization, but were completely prevented by alpha-adrenergic blockade (phentolamine or ergotamine). Neither ergotamine, phentolamine, nor methoxamine had any direct effects on adenyl cyclase activity. Phentolamine did not attenuate the increase in force development produced by paired electrical stimulation, suggesting that it does not block the entry of calcium into the muscle. In summary, methoxamine produced a dose-related increase in force development of the cat papillary muscle that was selectively blocked by alpha-adrenergic receptors in ventricular myocardium.

Adenylyl Cyclases↗

PubMed1976

Interactions between antimigraine drugs and a high affinity uptake and storage mechanism for 5-hydroxytryptamine.

Rabbit hearts removed 3H-5-hydroxytryptamine (3H-5-HT) from a perfusion concentration of 2.6 X 10(-9) g/ml. 15.8% of the extractable cardiac total radioactivity consisted of metabolites, mainly 5-hydroxyindoleacetic acid, and metabolism appeared in the perfusion fluid during the course of the perfusion. Ergotamine tartrate (1.0 X 10(-6) g/ml) caused a small increase in 3H-5-HT uptake by the heart. Methysergide bimaleate (1.0 X 10(-6) g/ml) slowed the appearance of metabolites in the perfusion fluid. Because of the high concentrations required, neither observation seems likely to be of clinical significance to migraine. The results do, however, suggest that the frequently observed sensitisation of tissues to 5-HT by ergotamine and methysergide is not the result of inhibition of its tissue uptake.

Animals↗

PubMed2000

Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications.

BACKGROUND: Serotonergic medications with various mechanisms of action are used to treat psychiatric disorders and are being investigated as treatments for drug dependence. The occurrence of fenfluramine-associated valvular heart disease (VHD) has raised concerns that other serotonergic medications might also increase the risk of developing VHD. We hypothesized that fenfluramine or its metabolite norfenfluramine and other medications known to produce VHD have preferentially high affinities for a particular serotonin receptor subtype capable of stimulating mitogenesis. METHODS AND RESULTS: Medications known or suspected to cause VHD (positive controls) and medications not associated with VHD (negative controls) were screened for activity at 11 cloned serotonin receptor subtypes by use of ligand-binding methods and functional assays. The positive control drugs were (+/-)-fenfluramine; (+)-fenfluramine; (-)-fenfluramine; its metabolites (+/-)-norfenfluramine, (+)-norfenfluramine, and (-)-norfenfluramine; ergotamine; and methysergide and its metabolite methylergonovine. The negative control drugs were phentermine, fluoxetine, its metabolite norfluoxetine, and trazodone and its active metabolite m-chlorophenylpiperazine. (+/-)-, (+)-, and (-)-Norfenfluramine, ergotamine, and methylergonovine all had preferentially high affinities for the cloned human serotonin 5-HT(2B) receptor and were partial to full agonists at the 5-HT(2B) receptor. CONCLUSIONS: Our data imply that activation of 5-HT(2B) receptors is necessary to produce VHD and that serotonergic medications that do not activate 5-HT(2B) receptors are unlikely to produce VHD. We suggest that all clinically available medications with serotonergic activity and their active metabolites be screened for agonist activity at 5-HT(2B) receptors and that clinicians should consider suspending their use of medications with significant activity at 5-HT(2B) receptors.

Dose-Response Relationship, Drug↗

PubMed1983

Jejunal atresia associated with Cafergot ingestion during pregnancy.

Fetal vascular accidents have been suggested as one cause for jejunal atresia due to in utero interruption of the superior mesenteric arterial supply to the intestines. Experimental studies support this hypothesis, and ergotamine has been shown to be a teratogen in experimental animals as a consequence of its vasoconstrictive action. We report the occurrence of intrauterine growth retardation and jejunal atresia in an offspring of a woman who also experienced four spontaneous abortions. During each of six pregnancies, the mother had taken as many as eight Cafergot tablets daily. We raise the hypothesis that Cafergot (1 mg ergotamine tartrate and 100 mg caffeine) might represent a vascular disruptive teratogenic agent during pregnancy. This hypothesis is supported by the clinical association of nonduodenal intestinal atresia with other defects that have a disruptive vascular etiology.

Abnormalities, Drug-Induced↗

PubMed1997

Uterine contraction in the development of Möbius syndrome.

We report a patient with Möbius syndrome. The birth defect in this child is probably the result of both vasoconstriction and uterine contractions brought on by ergotamine taken during the sixth week of pregnancy. We propose that vasoconstrictive or mechanical effects, or both, of abortifacient drugs such as ergotamine and misoprostol may account for other cases of Möbius syndrome, and we suggest that uterine contraction from any cause, at about the sixth or seventh week of pregnancy, may cause this birth defect. Further observational studies are needed to verify this hypothesis.

Abnormalities, Drug-Induced↗