ergoline and Migraine-Disorders

The initial association between the development of valvular heart disease and drugs stems from observations made during the use of methysergide and ergotamine for migraine prophylaxis in the 1960s. Since then, the appetite suppressants fenfluramine and dexfenfluramine, the dopamine agonists pergolide and cabergoline, and more recently, the recreational drug ecstasy (3,4 methylenedioxymethamphetamine; MDMA) have been implicated. Results from clinical trials show that drug dose and treatment duration affect both the risk of developing the disease and its severity. The natural history of the disease remains unclear, although regression of valvular lesions after the end of treatment has been reported. Interference with serotonin metabolism and its associated receptors and transporter gene seems a likely mechanism for development of the drug-induced valvular heart disease. Physicians need to balance the benefits of continued therapy with these drugs against possible risks. Further investigation is needed to assist with treatment decisions. Continued vigilance is necessary because several commonly prescribed treatments interact with serotonergic pathways.

Topics: Antiparkinson Agents; Appetite Depressants; Cabergoline; Dexfenfluramine; Dopamine Agonists; Drug Monitoring; Ergolines; Ergotamine; Fenfluramine; Fibrosis; Heart Valve Diseases; Heart Valves; Humans; Methysergide; Migraine Disorders; N-Methyl-3,4-methylenedioxyamphetamine; Patient Selection; Pergolide; Receptors, Serotonin; Serotonin Agents; Serotonin Plasma Membrane Transport Proteins; Vasoconstrictor Agents

Topics: Adult; Age Factors; Brain Diseases; Child; Child, Preschool; Diagnosis, Differential; Electroencephalography; Epilepsy; Ergolines; Ergotamine; Female; Humans; Hypersensitivity; Hypothalamus; Maleates; Methysergide; Migraine Disorders; Personality; Serotonin; Stress, Psychological; Time Factors

Topics: Animals; Blood Pressure; Clinical Trials as Topic; Cycloheptanes; Cyproheptadine; Dogs; Ergolines; Guinea Pigs; Haplorhini; Headache; Histamine H1 Antagonists; Humans; Hypnotics and Sedatives; Lethal Dose 50; Methysergide; Mice; Migraine Disorders; Phenothiazines; Piperidines; Rabbits; Rats; Serotonin Antagonists; Thiophenes; Vascular Headaches

In an open multicenter study involving 420 patients lisuride proved to be an effective and well-tolerated migraine prophylactic. In 61.4% of the patients the frequency of migraine attacks was reduced by more than 50% during the 3 month treatment period; the severity and duration of remaining attacks were markedly reduced. In the overall assessment, the effect was regarded as good to excellent in 69.7% of the patients and tolerance was good to excellent in 94.2%. The most common side effects were nausea (4.0%), vertigo (3.1%), drowsiness (1.4%). Prognostic criteria for the response to lisuride could not be identified.

Topics: Adult; Ergolines; Female; Humans; Lisuride; Male; Migraine Disorders; Multicenter Studies as Topic; Prognosis

Topics: Adult; Clinical Trials as Topic; Ergolines; Female; Humans; Male; Middle Aged; Migraine Disorders; Nicergoline

Lisuride is an ergot derivative which acts on serotonin and dopamine receptors at both peripheral and central levels. According to the central theory of headache, lisuride is an active prophylactic drug in adult headache sufferers. Because of its activity on dopamine receptors, a hypotensive action has been observed after acute and chronic administration of high doses of the drug in adults. An open trial on 45 migrainous children was carried out, to compare lisuride with pizotiphene treatment. Some 23 children were treated with lisuride and 22 with pizotiphene for 42 days. No statistically significant difference in therapeutic results between the two groups was found. Eight migrainous children were treated with a single oral dose of lisuride (0.0250 mg) and arterial blood pressure was measured before and after the drug. No significant change in either supine or orthostatic blood pressure was recorded in pre-drug and post-drug values. This study shows that lisuride is an effective and well-tolerated prophylactic drug in migrainous children.

Topics: Adolescent; Blood Pressure; Child; Ergolines; Female; Humans; Lisuride; Male; Migraine Disorders; Pizotyline; Posture

Topics: Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Ergolines; Humans; Migraine Disorders; Placebos; Urea

In the present double-blind clinical trial an isoergolenyl derivative with periphal antiserotonin, central dopaminergic activity and alpha-increasing effect on the human EEG, lisuride hydrogen maleate, was tested against placebo in a six-month trial involving 240 patients. Lisuride in long-term administration significantly reduces the frequency of migraine attacks in comparison to placebo. Its advantages are good tolerance and minimal side-effects. It is therefore concluded that lisuride is a suitable and effective drug for the prevention of migraine.

Topics: Clinical Trials as Topic; Double-Blind Method; Ergolines; Humans; Lisuride; Migraine Disorders; Placebos

Topics: Adult; Clinical Trials as Topic; Ergolines; Female; Humans; Male; Maleates; Methysergide; Middle Aged; Migraine Disorders; Urea

Topics: Adult; Cerebrovascular Circulation; Chronic Disease; Clinical Trials as Topic; Czechoslovakia; Drug Evaluation; Ergolines; Female; Humans; Male; Middle Aged; Migraine Disorders; Pizotyline; Serotonin Antagonists; Sweden; Thiophenes; Urea

Based on "quantitative pharmaco-EEG" using computer-analyzed EEG (CEEG) measurements, unknown CNS effects of lisuride hydrogen maleate (LHM) were established. CEEG profiles of LHM in low dosages (less than or equal to 10 mcg) are similar to CNS "inhibitory" compounds, while in higher dosages (25 mcg to 100 mcg) they resemble "psychostimulant" compounds. By measuring the brain function using computer period analysis of cerebral biopotentials, dose-efficacy relations were found (in the range of 25-75 mcg) which suggest the bioavailability of LHM at the CNS level. By comparing the CEEG profiles of LHM with the previously studied compounds, five different clinical uses of LHM were predicted. The pilot trials suggest that LHM may have therapeutic potentials in patients with "aging" and/or organic brain syndromes, and in children with behavioral disturbances.

Topics: Adolescent; Adult; Aged; Biological Availability; Child; Child, Preschool; Clinical Trials as Topic; Computers; Dementia; Dextroamphetamine; Diazepam; Drug Evaluation; Electroencephalography; Ergolines; Humans; Hyperkinesis; Isocarboxazid; Methylphenidate; Middle Aged; Migraine Disorders; Obesity; Pilot Projects; Psychophysiologic Disorders; Psychotropic Drugs; Schizophrenia; Urea

Topics: Animals; Blood Pressure; Clinical Trials as Topic; Cycloheptanes; Cyproheptadine; Dogs; Ergolines; Guinea Pigs; Haplorhini; Headache; Histamine H1 Antagonists; Humans; Hypnotics and Sedatives; Lethal Dose 50; Methysergide; Mice; Migraine Disorders; Phenothiazines; Piperidines; Rabbits; Rats; Serotonin Antagonists; Thiophenes; Vascular Headaches

The effectiveness of five different serotonin antagonists in the prevention of migraine was compared in 290 patients followed for periods of up to three years. Methysergide 3-6 mg. daily was most effective, with 20% of treated patients becoming headache-free and a further 44% remaining more than "half improved." The corresponding figures for BC105 were 10% and 40%, respectively.The results with BC105 were significantly better than those with placebo (P<0.02). The total improvement rates with methdilazine (45%) and cyproheptadine (43%) were better than those with placebo (32%) but did not achieve statistical significance. A new preparation, methylergol carbamide maleate, which is chemically related to methysergide, did not give better results than placebo.

Topics: Clinical Trials as Topic; Cyproheptadine; Ergolines; Female; Histamine H1 Antagonists; Humans; Male; Methysergide; Migraine Disorders; Muscle Cramp; Nausea; Phenothiazines; Placebos; Pyrrolidines; Serotonin Antagonists; Thiophenes

Topics: Amides; Body Temperature; Clinical Trials as Topic; Cyproheptadine; Ergolines; Female; Humans; Male; Maleates; Menstruation; Methysergide; Migraine Disorders; Phenothiazines; Serotonin Antagonists; Thermography; Thiophenes

Topics: Clinical Trials as Topic; Cyproheptadine; Ergolines; Humans; Methysergide; Migraine Disorders; Phenothiazines; Placebos; Serotonin Antagonists; Thiophenes; Urea

Topics: Brain; Cabergoline; Central Nervous System Agents; Child; Dopamine Agonists; Ergolines; Fructose; Humans; Male; Migraine Disorders; Pituitary Neoplasms; Prolactinoma; Topiramate

The clinical characteristics of 84 patients with pituitary tumour who had troublesome headache were investigated. The patients presented with chronic (46%) and episodic (30%) migraine, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT; 5%), cluster headache (4%), hemicrania continua (1%) and primary stabbing headache (27%). It was not possible to classify the headache according to International Headache Society diagnostic criteria in six cases (7%). Cavernous sinus invasion was present in the minority of presentations (21%), but was present in two of three patients with cluster headache. SUNCT-like headache was only seen in patients with acromegaly and prolactinoma. Hypophysectomy improved headache in 49% and exacerbated headache in 15% of cases. Somatostatin analogues improved acromegaly-associated headache in 64% of cases, although rebound headache was described in three patients. Dopamine agonists improved headache in 25% and exacerbated headache in 21% of cases. In certain cases, severe exacerbations in headache were observed with dopamine agonists. Headache appears to be a significant problem in pituitary disease and is associated with a range of headache phenotypes. The presenting phenotype is likely to be governed by a combination of factors, including tumour activity, relationship to the cavernous sinus and patient predisposition to headache. A proposed modification of the current classification of pituitary-associated headache is given.

Topics: Adenoma; Adult; Aminoquinolines; Antineoplastic Agents, Hormonal; Bromocriptine; Cabergoline; Disability Evaluation; Dopamine Agonists; Ergolines; Female; Headache; Humans; Male; Migraine Disorders; Octreotide; Peptides, Cyclic; Pituitary Neoplasms; Severity of Illness Index; Somatostatin; Time Factors

Topics: Antineoplastic Combined Chemotherapy Protocols; Brain; Bromocriptine; Cabergoline; Carotid Arteries; Dopamine Agonists; Ergolines; Horner Syndrome; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Migraine Disorders; Neoplasm Recurrence, Local; p-Hydroxyamphetamine; Pituitary Neoplasms; Prolactin; Prolactinoma; Remission Induction

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.

Topics: Animals; Binding, Competitive; Choroid Plexus; Dihydroergotamine; Ergolines; Ergotamine; In Vitro Techniques; Inositol Phosphates; Migraine Disorders; Piperazines; Receptors, Serotonin; Serotonin; Swine; Thermodynamics

The effect of nicergoline on cerebral blood flow (CBF), cerebrovascular resistance, the constriction of cerebral vessels caused reflectorily or by 5-hydroxytryptamine (5-HT) and on the transport of 5-HT in rat brain synaptosomes was studied using different experimental models. Nicergoline reduced cerebrovascular resistance in the carotid and vertebrobasilar system. The drug decreased carotid blood flow and local cortical CBF, preceded in some experiments by short-lasting CBF increase. Nicergoline almost completely inhibited brain vessels responses in the carotid and vertebrobasilar systems after tibial nerve stimulation. Simultaneously, inhibition of reflectory discharges of the sympathetic nerves was observed. Nicergoline showed an antiserotonin action by antagonizing the 5-HT effect on the cerebral circulation and inhibiting 5-HT-induced constriction of isolated rabbit basilar artery. The inhibition of uptake and enhancement of the release of 5-HT from brain synaptosomes indicates its ability to affect neuronal transmission in serotoninergic neurons. The effects of nicergoline are probably involved in the realization of its antimigraine action.

Topics: Animals; Basilar Artery; Cats; Cerebrovascular Circulation; Disease Models, Animal; Ergolines; In Vitro Techniques; Male; Migraine Disorders; Muscle Contraction; Muscle, Smooth, Vascular; Nicergoline; Rabbits; Rats; Serotonin; Synaptosomes; Vascular Resistance

Topics: Adolescent; Child; Dihydroergotamine; Electroencephalography; Ergolines; Female; Humans; Lisuride; Male; Migraine Disorders

Clinical experience of lysuride maleate acid in the treatment of 88 patients with occasional and 12 patients with chronic headache is reported. After 3-5 months observations the treatment was judged effective (excellent, good, satisfactory) in 72% of the cases and ineffective (poor, nil) in 28%. Side effects were few and short-lived, consisting mainly of slight nausea and asthenia. In 2 cases treatment was suspended as ineffective (in the patient's opinion).

Topics: Adolescent; Adult; Aged; Drug Evaluation; Ergolines; Female; Humans; Lisuride; Male; Middle Aged; Migraine Disorders; Sleep Initiation and Maintenance Disorders; Speech Disorders; Tremor

Topics: Adult; Bromocriptine; Drug Evaluation; Ergolines; Female; Humans; Menstruation; Middle Aged; Migraine Disorders; Premenstrual Syndrome

Topics: Bromocriptine; Ergolines; Humans; Levodopa; Migraine Disorders; Prolactin

Topics: Brain; Depression, Chemical; Electroencephalography; Ergolines; Humans; Migraine Disorders; Urea

Topics: Adult; Carbon Dioxide; Cerebral Arteries; Cerebrovascular Circulation; Ergolines; Humans; Male; Migraine Disorders; Papaverine; Partial Pressure; Vasomotor System

Topics: Adult; Aged; Cerebrovascular Disorders; Ergolines; Erythrocytes; Female; Giant Cell Arteritis; Headache; Humans; Hypertension; Male; Meningitis; Metabolic Clearance Rate; Middle Aged; Migraine Disorders; Osteoarthritis; Serotonin Antagonists; Sinusitis; Urea; Vascular Headaches

Topics: Adolescent; Adult; Aged; Asthma; Child; Chronic Disease; Conjunctivitis; Eczema; Ergolines; Female; Humans; Hypersensitivity; Male; Meniere Disease; Middle Aged; Migraine Disorders; Rhinitis, Allergic, Seasonal; Urea; Urticaria

Topics: Analgesics; Cerebrovascular Disorders; Ergolines; Ergotamine; Headache; Humans; Hypertension; Hypnotics and Sedatives; Metabolic Diseases; Methysergide; Migraine Disorders; Psychotherapy; Tranquilizing Agents

1. Platelets were incubated with methysergide and related compounds (2-bromo lysergic acid (BOL), ergotamine and methyl ergotamine) together with reserpine.2. Methysergide inhibited the normal aggregation response of platelets to 5-hydroxytryptamine (5HT) but did not affect the reduction in the 5HT content caused by reserpine, or the uptake of 5HT by the platelets.3. BOL, ergotamine and methyl ergotamine behaved similarly. Methysergide had greater anti5HT potency than BOL, and methyl ergotamine had greater potency than ergotamine.4. The use of platelets as a model for synaptic preparations is discussed.5. The role of 5HT receptor sites on the platelet membrane and the significance of the results for migraine patients treated with methysergide are discussed.

Topics: Blood Platelets; Bromine; Ergolines; Ergotamine; Humans; In Vitro Techniques; Methysergide; Migraine Disorders; Reserpine; Serotonin Antagonists

A review is presented of a distinctive type of vascular headache and its stereotyped features are emphasized, viz. severe non-throbbing character, unilateral and usually peri-ocular localization, frequent nocturnal occurrence and tendency to occur in brief episodes in a clustered pattern over weeks or months, with headache-free periods lasting months or years.Ten illustrative case histories are given and a plea is made for the early clinical recognition of this entity so that patients will not be submitted to unnecessary and potentially hazardous investigative procedures. While the common analgesics and narcotics are usually ineffective, ergotamine derivatives, methysergide and a new compound, BC-105, are highly effective forms of therapy.

Topics: Adult; Ergolines; Female; Humans; Male; Methysergide; Middle Aged; Migraine Disorders

Topics: Animals; Antihypertensive Agents; Behavior, Animal; Blood Pressure; Dose-Response Relationship, Drug; Ergolines; Evaluation Studies as Topic; Hallucinogens; Humans; In Vitro Techniques; Lysergic Acid Diethylamide; Migraine Disorders; Rats; Serotonin Antagonists; Stomach; Sympatholytics; Urea

Topics: Body Temperature; Cycloheptanes; Cyproheptadine; Ergolines; Female; Humans; Menstruation; Methysergide; Migraine Disorders; Phenothiazines; Piperidines; Progesterone; Reserpine; Serotonin Antagonists; Skin Temperature; Thermography; Thiophenes; Urea

Topics: Ergolines; Headache; Humans; Methysergide; Migraine Disorders; Serotonin Antagonists

Topics: Ergolines; Humans; Male; Methysergide; Middle Aged; Migraine Disorders; Retroperitoneal Fibrosis; Urinary Tract Infections

Topics: Adolescent; Adult; Ergolines; Female; Humans; Male; Methysergide; Middle Aged; Migraine Disorders; Serotonin Antagonists