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PubMed1986

Effects of ergot alkaloids on stress-induced analgesia.

Repeated, thirty minute anticipation of unavoidable painful stimulation causes endorphin-induced analgesia in rats. This type of stress-induced analgesia (SIA) develops rapidly during the first minutes of the exposure to anticipation stress. SIA can be demonstrated during the whole period of anticipation stress. Ergot drugs (DH--ergotoxine, lisuride, trans-9,10 dihydrolisuride) administered 30 min before the onset of anticipation stress, blocked completely this form of SIA. On the other hand, no effect of ergot alkaloids in the tail-flick latency, as measured under resting conditions, was observed. Possible interactions of ergot alkaloids with opiate receptors as an important mechanism by which ergot drugs affect SIA are discussed.

Animals↗
PubMed1986

[Vascular changes in sporadic ergotism. Epidemiology, pathogenesis, clinical picture and diagnosis with particular consideration of angiographic documentation].

Whereas the epidemic form of ergotism has been rare in the 20th century, the sporadic form has a wide distribution as a consequence of therapy with ergot-derivative drugs. Favourable prognosis of the condition, with complete recovery from the ischemic peripheral circulatory disorders can be obtained by early diagnosis. Precise evaluation of the history, with recognition of treatment of migraine headache or postpartum hemorrhage with ergot alkaloids, can be determinative in diagnosis. The specific pattern of the angiographic findings, as we saw it in 6 cases within the last 4 years, decisively confirms the diagnosis. We could demonstrate thread-, thorn- and hour glass-like narrowing of the vessels, due to spasm. Total occlusion with the development of collaterals may occur, but we saw no thrombus formation. The stenotic arterial segments had smooth margins. The distribution of the involved arteries was more focal than generalized and more peripheral than central. In two cases spasm could be abolished immediately by a pharmaceutical (i.a. injection of tolazoline) or by anesthetic procedures (halothane). The phenomenologic data, together with the complete reversal of the circulatory ischemic disorders after therapy (particularly the absolute ban of ergots) in most cases, is so specific that other diseases of ischemic nature (emboli, arteriosclerosis, Buerger's disease, fibromuscular hyperplasia) can be excluded.

Adult↗
PubMedDate not supplied

Liquid chromatographic determination of ergot alkaloids in wheat.

A method is described for the determination of individual ergot alkaloids in wheat. The sample is extracted with ethyl acetate-4% ammonium hydroxide (100 + 10), and the extract is cleaned up by liquid-liquid partition. The ergot alkaloids are resolved by liquid chromatography (LC), using a porous cross-linked polystyrene-divinylbenzene resin column and a mobile phase consisting of acetonitrile-0.05 M dibasic ammonium phosphate (55 + 45) buffered at pH 10.0. The ergot alkaloids ergonovine, ergonovinine, ergotamine, ergotaminine, alpha-ergocryptine, alpha-ergocryptinine, ergocristine, and ergocristinine are separated by LC and detected with a fluorescence detector. Recovery of ergot alkaloids added to wheat at levels of 16-760 ng/g averaged 85.6% with a coefficient of variation of 11.1%.

Chromatography, Liquid↗
PubMed1980

[Ano-cutaneous gangrenous ergotism].

A case of ergotism by abuse of ergotamine tartrate suppositories is reported. The patient developed the clinical picture of ergotism with multiple perianal ulcers. After ergot had been withdrawn there was a spontaneous healing of these ulcers after a few weeks. It is well known that ergot abuse can develop severe vascular spasm in the arteries, but it is unknown that cutaneous ulcers may occur by topical application.

Adult↗
PubMed1981

Enhancement of the intestinal absorption of ergot peptide alkaloids in the rat by micellar solutions of polyoxyethylene-24-cholesteryl ether.

The incomplete intestinal absorption of hydrogenated ergot peptide alkaloids as measured in bile duct cannulated rats is much increased when the ergot compounds are administered as micellar solutions together with POE-24-cholesteryl ether. In vitro diffusion experiments with isolated intestinal mucus show that the ergot peptide alkaloids are strongly retained by the mucus layer. It is suggested that the diffusion of the ergot compounds across the mucus barrier is facilitated by micellar entrapment of the drug.

Animals↗
PubMed1992

Usefulness of CV 205-502 in a case of allergy to ergot-derived drugs.

This study reports a case of allergy to ergot-derived drugs in a patient with a prolactin (PRL)-secreting microadenoma. The anamnesis revealed allergic reactions to the administration of analgesics and antibiotics. The administration of dopamine agonist drugs, such as bromocriptine (BRC; 2.5 mg) or lisuride (0.2 mg), induced after a few minutes the appearance of nausea, vomiting, postural hypotension, headache, edema of the glottis with dispnea and acroedema. The edemas disappeared a few hours after the administration of antihistaminic drugs while nausea, vomiting, postural hypotension and headache persisted for a few days. Therefore, the patient was tested with another dopamine agonist non-ergot-derived drug, quinagolide (CV 205-502), which did not cause side effects or allergic reactions. Furthermore, not only was the responsiveness to the drug optimal but it also normalized the PRL levels, and menses reappeared after more than a 5-year amenorrhea. This report suggests that ergot-derived drugs, such as lisuride and BRC, seldom induce allergic reactions apart from common side effects. Consequently, the feasibility of using a new drug with a different molecular structure (non-ergot derived) effective in the therapy of hyperprolactinemic syndromes represents a good alternative to conventional therapy.

Adult↗
PubMed1983

Long-acting ergot: clinical and neuroendocrinological aspects in migraine patients.

The possible interaction between long-acting ergot and the opiate system has been studied in 12 migraine patients, evaluating the PRL releasing effect of morphine. Our data suggest the integrity of the opiate system in migraine patients and demonstrate that long-acting ergot does not interact with the dopaminergic system. We hypothesize that the effect of ergot on migraine pain may be related to the interaction with non-opiate substances with central analgesic action. Chronic treatment with long-acting ergot significantly reduces the peak of pain intensity of the migraine attack.

Adult↗
PubMed2002

Fibrosis due to ergot derivatives: exposure to risk should be weighed up.

(1) Ergot derivatives are used for a variety of indications, including migraine, Parkinson's disease, endocrine disorders, and cognitive and neurosensory deficits in elderly people. (2) Fibrosis is a common complication of treatment with ergot derivatives. (3) Retroperitoneal fibrosis is the commonest form. Pleuropulmonary and pericardial fibrosis also occur. (4) Cardiac valve damage has been linked to some ergot derivatives. (5) Fibrosis occurs during long-term treatment. (6) Renal, pulmonary and cardiac complications can be serious. The fibrosis is often reversible if the drug is stopped quickly. (7) In practice, this risk of serious adverse effects tips the scales against these drugs for poorly established indications such as cognitive and neurosensory deficits in elderly people. The possibility of drug induced fibrosis should be considered at the first sign of renal, cardiac or pulmonary fibrosis in a patient on ergot derivatives.

Dihydroergotamine↗
PubMed1992

[Ergotism of the locomotor apparatus--a sometimes forgotten diagnosis?].

The alcaloids from rye-ergot are known and used for their vasoconstrictive properties, which can induce secondary ergotism. The extremities will be particularly involved. Vasoconstriction will also concern the gastrointestinal tract as well as the peripheric and the central nervous system, possibly with neuro-psychiatry symptoms. Cardiac and renal involvement has been described. Migraine, thrombosis prophylaxis and obstetrical situations are the most frequent therapeutic indications. Precise patient history, clinical and the typical angiological findings are necessary for diagnosis. The importance of an early diagnosis is emphasized. The responsible agent can then be stopped with thorough in-time vasodilatating treatment, and restitution will occur. Three cases are reported. The patients were referred to the rheumato-orthopedic clinic because of limbs claims. They suffered from different grades of ergotism, and one had to be amputated at the right hand. The following discussion is based on a review of the literature.

Adult↗
PubMed1984

Modern ergotism.

A patient taking excessive amounts of an ergot alkaloid for the treatment of migraine headaches developed cool, painful, swollen lower extremities with intermittent claudication and sensory changes. Symptoms subsided and pulses returned within a day of cessation of therapy. "St. Anthony's fire" may be due to stimulation of alpha-adrenergic receptors in the peripheral vasculature. Rebound headache after withdrawal of ergot alkaloids may lead to self-medication and overdosage, with subsequent risk of ergotism.

Caffeine↗
PubMed1975

Ergotism.

Severe extremity ischemia developed in four patients who had ingested methysergide maleate or ergot for the relief of headache. Symptoms involved the upper extremity in two patients and the lower extremity in two. Spontaneous reversal of the ischemic picture was obtained by simple discontinuation of ergot in most instances, although intra-arterial vasodilators were used in one case. Angliography disclosed arterial spasm and was a useful adjunct in confirming the cause of ischemia in each of the patients. It was especially useful when a history or ergot ingestion was not immediately available.

Adult↗
PubMedDate not supplied

Use of cyclodextrins for the enantioselective separation of ergot alkaloids by capillary zone electrophoresis.

Ergot alkaloid enantiomer derivatives were resolved using capillary zone electrophoresis. The effect of cyclodextrins, added to the background electrolyte, on the migration time and the resolution was studied. Good separation for epimeric ergot alkaloid derivatives was also obtained using phosphate buffer at pH 2.5. Separation was improved by supplementing the background electrolyte with 30 mM of gamma-cyclodextrin. Good resolution of racemic ergot alkaloid derivatives in their enantiomers was achieved in a background electrolyte containing either beta-cyclodextrin or its derivative, or gamma-cyclodextrin.

Cyclodextrins↗
PubMed2000

Progress and prospects of ergot alkaloid research.

Ergot alkaloids, produced by the plant parasitic fungi Claviceps purpurea are important pharmaceuticals. The chemistry, biosynthesis, bioconversions, physiological controls, and biochemistry have been extensively reviewed by earlier authors. We present here the research done on the organic synthesis of the ergot alkaloids during the past two decades. Our aim is to apply this knowledge to the synthesis of novel synthons and thus obtain new molecules by directed biosynthesis. The synthesis of clavine alkaloids, lysergic acid derivatives, the use of tryptophan as the starting material, the chemistry of 1,3,4,5-tetrahydrobenzo[cd]indoles, and the structure activity relationships for ergot alkaloids have been discussed. Recent advances in the molecular biology and enzymology of the fungus are also mentioned. Application of oxygen vectors and mathematical modeling in the large scale production of the alkaloids are also discussed. Finally, the review gives an overview of the use of modern analytical methods such as capillary electrophoresis and two-dimensional fluorescence spectroscopy.

Animals↗
PubMed1990

Actions of non-peptide ergot alkaloids at 5-HT1-like and 5-HT2 receptors mediating vascular smooth muscle contraction.

This report describes the actions of the non-peptide ergot alkaloids methysergide, methylergometrine and ergometrine at two types of 5-HT receptor mediating vascular contraction; the well established 5-HT2 receptor in rabbit aorta and a non-5-HT2 receptor in rabbit saphenous vein which resembles the 5-HT1-like receptor in dog saphenous vein. In the rabbit aorta ergometrine (1 mumol/l) and methylergometrine (0.3 mumol/l), but not methysergide, produced small contractions (14% and 7% respectively of the maximal response to 5-HT). This contraction was not related to activation of 5-HT2 receptors since it was resistant to blockade by ketanserin (0.3 mumol/l). When examined as antagonists of 5-HT-induced contractions of rabbit aorta, each ergot displayed nanomolar affinity at the 5-HT2 receptor but only methysergide behaved as a simple competitive antagonist (pKB = 8.25). Methylergometrine and ergometrine produced surmountable blockade which was accompanied by a non-parallel displacement of the 5-HT concentration-effect curves. The selective 5-HT1-like receptor agonist GR43175 (less than or equal to 30 mumol/l) was devoid of affinity at the 5-HT2 receptor in rabbit aorta. In the rabbit saphenous vein each of the ergots produced concentration-dependent contractions which resulted in overtly biphasic concentration-effect curves. Only the first phase of contraction mimicked the effects of 5-HT and GR43175 since contractions were not blocked by MDL 72222 (1 mumol/l), but were surmountably antagonised by methiothepin (10 nmol/l), ketanserin (0.3 mumol/l) and spiperone (0.3 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

Nitroglycerin for ergotism. Experimental studies in vitro and in migraine patients and treatment of an overt case.

Ergotamine was used to induce arterial contraction in vitro (measurement of isometric tension in segments from 3 human temporal arteries) and in vivo (peripheral systolic blood pressure measured by strain gauge plethysmography in 5 migrainous patients). In both these models of ergotism, the directly acting vasodilator nitroglycerine (NTG) effectively relieved the ergotamine-induced arterial contractions. A case of ergotism treated successfully with NTG infusion is reported. The diagnosis was based on history and measurement of peripheral systolic blood pressure by strain gauge plethysmography. The latter technique was also used to monitor the response to treatment for 20 h. Blood levels of ergotamine during ergotism were in the therapeutic range. Possible explanations for this finding are discussed.

Adult↗
PubMed1987

Ergotism presenting as restenosis following angioplasty.

Ergotism may cause isolated lower-extremity arterial stenoses that appear amenable to angioplasty but that will recur if the causative agent is not withdrawn. A case of femoral-popliteal stenosis caused by surreptitious ergot ingestion is presented. The lesion initially responded to angioplasty but quickly recurred, whereupon discovery of ergot use and withdrawal of the compound led to the disappearance of symptoms.

Angioplasty, Balloon↗
PubMed1976

Ergot alkaloids as dopamine agonists: comparison in two rodent models.

A series of ergot alkaloids, together with the DA agonists apomorphine and piribedil, were tested for protective effects against audiogenic seizures in an inbred strain of mice (DBA/2) and for induction of circling behaviour in mice with unilateral destruction of one nigrostriatal DA pathway. The order of potency against audiogenic seizures was apomorphine greater than ergocornine greater than bromocryptine greater than ergometrine greater than LSD greater than methysergide greater than piribedil while that observed in the rotating mouse model was apomorphine greater than ergometrine greater than ergocornine greater than bromocryptine greater than piribedil. LSD caused only weak circling behaviour even when administered in high doses (greater than 1 mg/kg). Methysergide was ineffective. Prior administration of the neuroleptic agent haloperidol blocked the effect of DA agonists and of ergot alkaloids in both animal models. The possible action of ergot alkaloids as DA agonists is discussed.

Acoustic Stimulation↗
PubMed1979

Effects of ergot drugs on serotonergic function: behavior and neurochemistry.

Several new ergot drugs were tested for behavioral and neurochemical effects related to serotonergic function. Lergotrile and bromocriptine potentiated the so-called "5-HT syndrome", a set of behaviours associated with increased serotonergic neurotransmission consequent to monoamine oxidase inhibition and tryptophan loading. Metergoline antagonized this behavior. In studies of receptor binding using 3H-5-HT or 3H-LSD, metergoline was the most potent at displacing specific ligand binding. Since the ergots also affect dopaminergic function, these results are discussed for their information on both dopaminergic and serotonergic actions of these drugs and their implications for clinical use of ergots.

5-Hydroxytryptophan↗