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PubMed1998

Oral and parenteral vaccination of mice with protein-ergotamine conjugates and evaluation of protection against fescue toxicosis.

Acremonium coenophialum produces ergopeptide alkaloids in tall fescue (Festuca arundinacea Schreb.). These ergot alkaloids decrease serum alkaline phosphatase (ALP) activity, serum cholesterol and prolactin concentrations, as well as average daily gains (ADG) in cattle. The objective of this study was to evaluate the protection of anti-ergotamine antibodies induced by either oral or parenteral vaccination with protein-ergotamine conjugates or passive vaccination with anti-ergovaline, monoclonal antibodies in a murine model of fescue toxicosis. Ergotamine (EG) was conjugated to bovine serum albumin (BSA) and cholera toxin subunit B (CTB) by the Mannich reaction. Mice were blocked based on weight and randomly allocated into five groups of 10 mice each. Treatment groups were as follows: (1) group vaccinated intraperitoneally (ip) with a BSA-EG conjugate and fed an endophyte-infected (EI) fescue diet (BSA-EG group); (2) group orally vaccinated with a CTB-EG conjugate mixed with free cholera toxin (CT) and fed an EI fescue diet (CTB-EG group); (3) nonvaccinated group fed an EI fescue diet (EI group); (4) group passively vaccinated with anti-ergovaline, monoclonal antibodies and fed an EI fescue diet (MoAB group); and (5) nonvaccinated group fed an endophyte-free (EF) fescue diet (EF group). The EI diet contained 1.5 ppm of Ergovaline (EV), whereas no EV was detected in the EF diet.Respective diets were similar upon nutritional analysis. Unvaccinated mice in the EI group exhibited features of fescue toxicosis as indicated by decreased serum ALP activity and cholesterol, and decreased weight gain as compared to mice in the EF group. Antibodies against EG and EV were present in sera of mice in the BSA-EG and MoAB groups, respectively. Mice orally vaccinated with the CTB-EG conjugate developed secretory IgA (sIgA) antibodies and short-lived, systemic IgG responses against EG. Weight gains were increased in the BSA-EG and CTB-EG groups and tended to be increased in the MoAB group vs. the unvaccinated EI group. Serum ALP activity was decreased in the BSA-EG and MoAB groups as compared to the EF group. Serum ALP activity was further decreased in the BSA-EG vaccinated group as compared to the EI group. Cholesterol concentrations were decreased in the EI, BSA-EG and MoAB groups as compared to the EF group. Prolactin concentrations were similar in all groups.

Acremonium↗
PubMed1982

Conformational analysis of the ergot alkaloids ergotamine and ergotaminine.

Conformational analyses by 1H NMR and potential-energy calculations are reported for the ergot alkaloids ergotamine and ergotaminine, both as free bases and as the protonated species. In the neutral forms in CDCl3. two strong intramolecular hydrogen bonds fix the molecules in folded conformations, but the protonated species adopt a more extended conformation, with a single intramolecular hydrogen bond. Of the 24 alternative conformations available to ergotamine, the most likely biologically active species in environments with low dielectric constants, e.g., the presumed ergotamine binding site, is the folded, hydrogen-bonded conformation observed for the neutral molecule in CDCl3 solution.

Chemical Phenomena↗
PubMed1999

Ergotamine-induced intermittent claudication.

We report about a female patient with intermittent claudication caused by ergotamine. She used ergotamine as a treatment for migraine headaches for more than 4 years. The claudication began 7 month before admission. Colour Doppler sonography and angiography showed severe stenosis of the left external iliac and superficial femoral artery. The patient was treated with phenprocoumon for one year after withdrawal of ergotamine. After that the superficial femoral stenosis disappeared completely, but the external iliac stenosis was still present and was consequently successfully treated by atherectomy. The histology showed a fibrosis of the intima and a hypertrophy of the media.

Adult↗
PubMed2000

Anti-inflammatory effects of ergotamine in steers.

The objective of this experiment was to investigate whether the ergot alkaloid, ergotamine (ET), an alkaloid used to model fescue toxicosis in cattle, modifies the response of cattle to endotoxin (LPS) challenge. Steers (n = 16) were divided into the following treatment groups: control (C), ergotamine (ET), endotoxin (LPS), and ET + LPS. ET and ET + LPS groups received a single bolus intravenous injection of ET (40 microg. kg. body wt(-1)), whereas C and LPS steers received a single bolus injection of sterile vehicle. Thirty minutes after ET/vehicle administration, a single bolus intravenous injection of LPS (0.2 microg. kg. body wt(-1)) was given. Blood was collected at various time points for 48 hr post. Endotoxin increased rectal temperature (RT) and the circulating levels of tumor necrosis factor-alpha (TNF-alpha), cortisol, haptoglobin (Hp), thromboxane B(2) (TXB(2)). The circulating Hp, TNF-alpha, and TXB(2) increases were blunted by pretreatment with ET compared with ET + LPS. Ergotamine by itself increased circulating cortisol and RT, whereas it decreased serum prolactin (PRL). Therefore, whereas administration of LPS at 0.2 microg/kg to steers resulted in an expected response, the combination of ET + LPS attenuated major effects of LPS alone. Thus, acute administration of ET appeared to be anti-inflammatory as it decreased the inflammatory response to LPS, an effect likely driven at least in part by the ET-caused cortisol increase.

Animal Feed↗
PubMed1993

Myocardial infarction after chronic ergotamine abuse.

As a result of chronic ergotamine abuse, reversible arterial narrowing has been documented angiographically in peripheral, but not in coronary arteries. We report on a patient with no cardiovascular risk factors, but because of chronic ergotamine abuse suffered on acute myocardial infarction, complicated by ventricular fibrillation. Coronary angiography performed 3 days after resuscitation revealed a distal occlusion of the left anterior descending artery. Three months later, spontaneous recanalization had occurred, and no residual narrowing was seen angiographically. Thus, surveillance of patients with migraine headache to avoid chronic ergotamine abuse is recommended to prevent cardiovascular complications.

Coronary Disease↗
PubMed1981

Effect of ergotamine on platelet prostaglandin synthesis--in vitro and in vivo experiments.

We studied the effect of ergotamine on the formation of metabolites of [1 - 14C] arachidonic acid by human blood platelets incubated with ergotamine (10(-5) or 5.10(-5)M) in vitro or after 0.5 mg i.m. administration in vivo. The in vitro experiments confirmed our earlier observation that ergotamine inhibits prostaglandin synthesis. This effect, however, seemed to be restricted to the toxic dose range of the drug as in vivo it occurred only in those subjects who became nauseated or vomited after administration of the drug.

Adolescent↗
PubMed1992

Lack of effect of the antimigraine drugs, sumatriptan, ergotamine and dihydroergotamine on arteriovenous anastomotic shunting in the dura mater of the pig.

1. In anaesthetized animals, the antimigraine drugs, sumatriptan, ergotamine and dihydroergotamine, reduce carotid arteriovenous anastomotic shunting. Within the carotid vascular bed arteriovenous anastomoses are located, amongst other places in the dura mater, which is a putative site of the pain during a migraine attack. 2. In this investigation, we have localized and measured the arteriovenous shunting within the carotid vascular bed of the pig by using simultaneous intracarotid injections of radiolabelled microspheres of three different sizes (10, 15 and 50 microns), which provides an index of blood flow via arteriovenous anastomoses larger than approximately 14, 27 and 90 microns diameter, respectively. The effects of sumatriptan (0.3 mg kg-1), ergotamine (0.02 mg kg-1), dihydroergotamine (0.1 mg kg-1) and saline were studied by repeating the injections of 15 and 50 microns spheres after the treatments. 3. There was no difference in shunting or entrapment between the 10 and 15 microns microsphere, indicating the absence of arteriovenous anastomoses with a diameter between 14 and 27 microns. 4. Arteriovenous anastomoses with a diameter between 27 and 90 microns, as indicated by the difference in blood flow measured by 15 and 50 microns spheres, were located in the dura mater, ears, skin, fat and, to a lesser extent, in the skeletal muscles and eyes. 5. Sumatriptan, ergotamine and dihydroergotamine reduced the overall flow in the smaller arteriovenous anastomoses (diameter between 27 and 90 microns), and even more in larger shunts (wider than 90 microns). 6. Locally, blood flow in the smaller arteriovenous shunts was reduced in the skin and fat, but not in the dura mater, ears, eyes and muscles.It is not possible to determine in which tissues blood flow in the larger arteriovenous anastomoses was reduced.7. Tissue blood flow measured with 15 gm microspheres remained unchanged after the three antimigraine drugs, implying a lack of effect on capillary flow.8. It is concluded that in the anaesthetized pigs the only evident effect of these antimigraine drugs on carotid haemodynamics is a decrease in blood flow in both smaller and larger arteriovenous anastomoses;the smaller arteriovenous anastomoses were affected in the skin and fat, but not in other tissues.

Animals↗
PubMed1970

Controlled clinical trial of ergotamine tartrate.

A double-blind controlled clinical trial of cross-over design for the treatment of headache was conducted in 88 women identified during a community survey as having headaches with the features of migraine. Of 79 subjects who completed the trial, 40 benefited from oral ergotamine tartrate and 46 benefited from the placebo. There was no evidence that ergotamine in doses of 2 or 3 mg. was more effective than the placebo. Ergotamine aggravated the attack significantly more often than the placebo. Neither the colour of the tablets nor the order of therapy significantly affected the results of the treatment.

Adult↗
PubMed1988

Birth defects following maternal exposure to ergotamine, beta blockers, and caffeine.

Ergotamine exposure during pregnancy has been suggested to cause birth defects which have a vascular disruptive aetiology. The present case provides additional support for the possible adverse fetal effects of exposure to ergotamine, caffeine, and propranolol during the first four months of pregnancy. At birth the infant showed evidence of early arrested cerebral maturation and paraplegia. The nature of these defects suggests a primary vascular disruptive aetiology. We hypothesise that ergotamine, acting either alone or in synergy with propranolol and caffeine, produced fetal vasoconstriction resulting in tissue ischaemia and subsequent malformation. This case raises the possibility that fetal malformation may result from concomitant use of multiple vasoconstrictive agents during pregnancy.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Ergotamine and cerebral blood flow.

We measured the cerebral blood flow (CBF) of 16 patients by the xenon-133 intracarotid method before and after the intramuscular injection of ergotamine tartrate. The regional and hemispheric CBF was unaltered, even in 3 migraneurs in who ergotamine relieved the headache. Ergotamine tartrate in therapeutic doses has no effect on the cerebral circulation.

Adult↗
PubMed2001

Ergotamine-induced acute vascular insufficiency of the lower limb--a case report.

Ergotamine-containing drugs are widely used in the treatment of acute migraine attacks. Spastic vasoconstriction is one of the possible side effects usually affecting the lower extremities and sometimes leading to gangrene. A 28-year-old woman was hospitalized for severe acute arterial insufficiency of the limbs. The initial surgical approach was not successful since the diagnosis was missed. Overuse of ergotamine derivative was acknowledged by the patient, who had a long history of migraine headaches. Therefore, the patient was treated conservatively with intravenous heparin and prostaglandin infusion and sympatheticolysis via epidural catheter. The vascular complications, angiographic findings, and different modalities of treatment of ergotamine-induced peripheral vascular insufficiency of the lower limb are reviewed.

Acute Disease↗
PubMed2004

Ergotamine as a possible cause of Möbius sequence: additional clinical observation.

A case of Möbius sequence after exposure to ergotamine during early development is reported. Vascular disruption is one of the theories explaining the pathogenesis of Möbius sequence. Ergotamine can cause vasospasm and a prolonged and marked increase in uterine tone. This is the second report suggesting a relation between maternal ingestion of ergotamine in early pregnancy and subsequent Möbius sequence in a child.

Ergotamine↗
PubMed2000

[Can the biologic pattern of cervicogenic headache change after overuse or withdrawal of ergotamine derivatives?].

The transformation of a primary headache into a chronic daily headache (CDH) may or may not be related to the overuse of pain-killers, as their influence on the pathophysiological mechanisms remain inconclusive. We describe three patients (female, aged 65 and 39 years, and male, 46) affected by cervicogenic headache (CH) and CDH linked to the overuse of pain-killers (ergotamine derivatives) that were submitted to the infiltration of the greater occipital nerve (GON). At the end of three days of treatment, a total improvement of the pain symptoms was recorded, which allowed for the withdrawal of the ergotamine derivatives. The CH cannot be ranked with the CDHs, since it presents an organic etiology; however, if the pain is daily and the diagnosis is belated, the indiscriminate and excessive use pain-killers may occur. In the cases described, the overuse of pain-killers did not affect the natural evolution of this headache after treatment with the infiltration of the GON, as all the patients who underwent infiltration showed a total improvement of their painful symptoms, without headache resulting from the withdrawal of pain-killers, nor did they show any pharmacological dependence. This is an evidence that the CH presents and organic etiology, not being influenced in its pathophysiology by the overuse of ergotamine derivatives.

Adult↗
PubMed1999

Tongue necrosis provoked by ergotamine tartrate and disclosing a giant cell arteritis.

A case of tongue necrosis induced by ergotamine tartrate is reported in a patient who was suffering from an unknown giant cell arteritis (GCA). The role of ergotamine in provoking tongue necrosis in temporal arteritis has only infrequently been considered. The hypothesis concerning ergotamine-induced vasospasm potentially being able to trigger a tongue necrosis in GCA is supported by the present case. This unusual complication warns us against uncritical prescription of this drug for elderly people suffering from migraine without considering GCA.

Aged↗
PubMed1999

Ventricular fibrillation secondary to ergotamine in a healthy young woman.

A 34-year-old woman collapsed secondary to ventricular fibrillation 3 hours following the ingestion of ergotamine tartrate for migraine. She underwent defibrillation and recovered rapidly without any subsequent consequences. The mechanism of action and the side effects of ergotamine and other antimigraine drugs are discussed. We hypothesize that a coronary spasm induced by ergotamine could be the aetiologic factor leading to ischaemic ventricular fibrillation.

Adult↗
PubMed2002

Successful treatment of threatening limb loss ischemia of the upper limb caused by ergotamine. A case report and review of the literature.

We report a case of ischemia limited to the upper limb caused by chronic use of ergotamine. The effect of this drug was not related to hypersensitivity or to the potentiating effects of other medications. The patient was successfully treated discontinuing ergotamine and administering an alpha-blocking agent for three months. A review of the literature of the vascular complications of ergotamine is presented.

Administration, Oral↗
PubMed1992

Ergotamine: its use in the treatment of migraine and its complications.

This paper gives a review of the use of ergotamine in the treatment of migraine and discusses its side effects and the treatment of possible complications. It is concluded that ergotamine is an effective and valuable substance in the treatment of acute attacks of migraine. However, ergotamine remains a potentially dangerous substance, its possible side effects being multiple and in some cases very serious. In view of the important adverse effects, the further study of other molecules effective in the treatment of acute migraine attacks is warranted.

Autonomic Nervous System Diseases↗
PubMed2003

[The effectiveness of ergotamine treatment in chronic headache disorders: a double-blind, randomized, crossover, placebo controlled trial].

BACKGROUND: Postulated mechanism of migraine headache is a result of vascular spasm (primary) and dilatation with edema of the perivascular space (secondary). Thus we use drugs not the only during acute phase of headache but in prevention, also. Drugs containing ergotamine are well known and were used for years in the treatment of migraines. In this study we tried to investigate the role of multicomponent drugs containing ergotamine in the treatment of migraine in the adult workers group. MATERIALS AND METHODS: Experiments were performed with the use of double blind, randomized, crossover, placebo controlled study. Drug, Hydacorn, is a multicomponent drug where one tablet contains 1 mg of dihydroergo-tamine, 40 mg of caffeine and 100 mg of diphenylhydantoine. 36 adults were enrolled (27 females and 9 males). Patients were examined 5 times every 2 weeks. During the 3rd visit the drug was changed to Hydacorn and placebo. RESULTS: During the 1st visit the intensity of pain did not differ significantly. After start of treatment the pain intensity did not differ significantly versus the 1st visit in placebo group. In the Hydacorn group we observed the significant reduction of pain intensity vs 1st visit and vs placebo. After drug change the significant reduction was present vs placebo (during the 5th visit only) and vs the 1st visit. Pain intensity during the 4th visit did not differ significantly vs placebo probably because of long action time for ergotamine. CONCLUSIONS: Our results suggest that Hydacorn is very effective and safe in the prevention of migraines.

Adolescent↗