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PubMed2002

Wilfred Harris' early description of cluster headache.

Wilfred Harris was a London neurologist with a significant interest in the treatment of neuralgia. Harris' descriptions of what he called migrainous neuralgia were the first recorded of cluster headache in the English medical literature. He was probably one of the first to describe the cluster phenomenon itself and the effectiveness of ergotamine in treating acute attacks of cluster headache. His seminal contributions to the clinical and therapeutic spectrum of cluster headache are reviewed.

Anatomy, Comparative↗
PubMed2003

Migraine prophylactic medication usage patterns in The Netherlands.

This study aims to investigate usage patterns of specific migraine prophylactic medications in ergotamine and triptan patients commencing this treatment for the first time during 1 January 1992 until 31 December 1998. Usage patterns of specific migraine prophylactic drugs were evaluated for each patient by accessing data from a large prescription database and were characterized as continued, switch or stop use during the patient observation period. Several patient and medication-related factors were explored in order to identify a possible relationship with the specific usage pattern defined. Approximately 75% of the study population (n = 729) had terminated (stop or switch) prophylactic treatment after 1 year. Age < 40 years (relative risk (RR) 1.9; 95% confidence interval (CI) 1.2-3.2) and the concomitant use of non-steroidal anti-inflammatory drugs (RR 3.2; 95% CI 1.2-5.5) or specific abortive migraine drugs resulted in a faster onset of treatment modification (switch). Overall, migraine prophylactic treatment is used for a relatively short period, probably attributable to the common limitations associated with migraine prophylaxis, such as poor compliance and/or limited therapeutic efficacy. Patterns of use can be influenced by a variety of factors, including age, type of prescriber and certain co-medication. Patient interview studies are required to clarify these issues further.

Adrenergic beta-Antagonists↗
PubMed1997

Identification and characterization of a new serotonergic recognition site with high affinity for 5-carboxamidotryptamine in mammalian brain.

We analyzed the existence of an additional serotonin (5-HT) receptor subtype, sensitive to 5-carboxamidotryptamine, in the mammalian brain. Radioligand binding studies with [3H]5-HT were carried out in rat, guinea pig, and human brain membranes, in the presence of unlabeled drugs to mask the binding to all known 5-HT receptors, with the exception of 5-HT1E sites. Under these conditions, unlabeled 5-carboxamidotryptamine still showed a biphasic competition curve with a nanomolar affinity component. Saturation studies with 5-[3H]carboxamidotryptamine were carried out in the presence of (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin, mesulergine, and ergotamine, to mask the binding to all receptors known to be labeled by 5-carboxamidotryptamine. These studies showed the existence in cortex and hippocampus from guinea pig and human brain of a remaining binding site with high affinity (pK(D) = 7.8-8.1) and a unique pharmacological profile. 5-HT and 5-carboxamidotryptamine showed nanomolar affinity, whereas 5-methoxytryptamine recognized this binding site with intermediate affinity. Other drugs exhibited low or very low potency in inhibiting this binding. The addition of 5'-guanylylimidodiphosphate significantly reduced the number of binding sites labeled by 5-[3H]carboxamidotryptamine, in the presence of the masking drugs described above, indicating the interaction with a GTP-binding protein. Preliminary autoradiographic studies in human brain appear to indicate that this 5-HT binding site is present in areas such as the globus pallidus, neocortex, and hippocampus, among others.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2002

Efficacy and tolerability of prochlorperazine buccal tablets in treatment of acute migraine.

OBJECTIVES: To study the efficacy and tolerability of prochlorperazine (PCZ) management of acute migraine. DESIGN AND METHODS: A double blind comparative study was conducted to assess the efficacy of buccal PCZ 3 mg compared with oral ergotamine tartarate 1 mg plus caffeine 100 mg (ERG) or placebo (buccal or oral) for treatment of acute migraine. In all, 114 episodes of acute migraine were evaluated. Patients graded symptoms on a four-point scale before and up to 4 hours after treatment. The primary efficacy parameters included headache resolution within 2 hours (grade 3 or 2 to grade 0) and alleviation of other accompanying symptoms of migraine. The supplementary endpoints included improvement in quality of life (QOL). RESULTS: The percentage of patients reporting resolution of headache (to grade 0) was 51.4% for buccal PCZ and 21.7% for buccal placebo, 23.1% for oral ERG and 28.6% for oral placebo, headache tended to recur in both the placebo and ERG groups after initial improvement. Buccal PCZ was well tolerated; no signs of local irritation were evident, and patients found the formulation easy to use. Mild but transient sedation and drowsiness were observed in 41%. CONCLUSIONS: In the present study, PCZ 3 mg via the buccal route produced faster improvement and greater efficacy than placebo (oral as well as buccal) or oral ERG. The global QOL score 2 hours after treatment scores was higher in the PCZ group. Buccal PCZ may represent a particularly effective alternative for acute migraine treatment.

Acute Disease↗
PubMed1993

[Critical ischemia of the extremities caused by ergotism. Treatment with intra-arterial prostaglandin E1 infusion].

Severe ischaemia of the left upper limb developed in a 42-year-old woman (who had suffered from migraine since the age of 6 years) after the intake of 12 mg ergotamine tartrate (six suppositories of Cafergot within 5 hours). The left hand became very painful and pale with loss of touch sensation, and she could not move her fingers. Selective catheter angiography demonstrated typical signs of vascular ergotism: arterial spasms, corkscrew-like collaterals and segmental arterial occlusions. The patient's symptoms began to improve 10 minutes after starting an intraarterial infusion of prostaglandin E1 (0.34 ng/kg per min over 10 hours). Sensory function in the fingers was restored after 24 hours and reactive hyperaemia had occurred. Radiological examination after 48 hours showed complete recovery. This case emphasizes the need for obtaining an exact history regarding drug intake in any case of acute peripheral vascular disorder, but especially if there is no pointer to arterial thromboembolism. Angiography is of value in the differential diagnosis of suspected ergotism. Intraarterial infusion of prostaglandin E1 has few side effects and is immediately effective.

Adult↗
PubMed1979

Cluster headache: relation to and comparison with migraine.

Numerous factors, such as location of pain, sex, frequency and pattern of occurrence, and symptoms, distinguish cluster headache from migraine. Cluster headache is characterized by severe unilateral periorbital pain. Attacks lasting from several minutes to several hours occur many times a day over a period of weeks to months. Opinions differ as to whether cluster headache is a variant of migraine or a completely different disorder. For relatively mild attacks, abortive treatment with ergotamine tartrate is usually successful. Cases which do not respond to abortive measures require prophylaxis.

Cluster Headache↗
PubMed1989

Four steps in managing migraine.

The first step in management of migraine is convincing the patient of the diagnosis. Once this has been accomplished, the physician needs to identify precipitating factors. Common migraine triggers include stress, menstruation, use of oral contraceptives, and certain foods. The next step is choosing appropriate therapy. Analgesics are most commonly prescribed in North America; nonsteroidal antiinflammatory drugs, ergotamine, narcotics, corticosteroids, and other drugs are also useful. Prophylactic therapy should be considered when treatment of individual attacks fails, causes adverse effects, or leads to dependence.

Analgesics↗
PubMed2001

Clinical ergotism induced by ritonavir.

Ritonavir strongly inhibits cytochrome P450, thus altering the metabolism of other drugs. We report on an HIV-positive man who, on his 13th day of ritonavir therapy, developed severe ergotism after self-administration of low doses of ergotamine. Drug interactions, the degree of responsibility of the patient and the availability of over-the-counter medications must be considered when prescribing antiretroviral therapy.

Adult↗
PubMed1981

Variability in the content and composition of alkaloids found in Canadian ergot. I. Rye.

The total alkaloid content and individual alkaloid composition were determined by colorimetry and high performance liquid chromatography, respectively, for Canadian rye ergot sclerotia. The total alkaloid content was highly variable between sclerotia from the same head, field, or region and ranged from 0.011 to 0.452% (av. 0.249%). Levels were lowest in ergot from Prince Edward Island. The individual alkaloid composition was uniform throughout a single sclerotium or in different sclerotia from the same head, somewhat uniform for averages in different fields throughout a region, but highly variable from head to head in a given field. On a regional basis, ergotamine followed by ergocristine were the major alkaloids observed in the east whereas the order was reversed in the west. Ergometrine, ergosine, ergocornine, and ergocryptine were also observed to a lesser degree; ergostine was not observed. Isomerization of ergometrine increased from near 0% in the east to about 40% in the west, but was relatively constant (about 30%) for the peptide alkaloids in all regions.

Canada↗
PubMed1986

Intraarterial sodium nitroprusside infusion in the treatment of severe ergotism.

Treatment of migraine with ergot alkaloids may produce systemic vasospasm in patients, especially as a result of automedication and overconsumption but also due to individual hypersensitivity. Peripheral vasoconstriction may lead to gangrene of the extremities, necessitating amputation. Various treatments have been tried against ischemic complications during ergotism with varied and unpredictable results. We report two recent cases of severe acute peripheral ischemia due to ergotamine abuse successfully treated with continuous systemic sodium nitroprusside infusion. The doses used during intraarterial injection are well below those known to be toxic. Consequently, the adverse effects of cyanide toxicity can be avoided. We think that intraarterial infusion of sodium nitroprusside, associated with forced diuresis and the administration of hydroxycobalamin, constitutes the treatment of choice of extreme peripheral ischemia of ergotism.

Adult↗
PubMed1977

Treatment of the premenstrual syndrome.

A placebo-controlled, randomized, double-blind, parallel group study in hospital and general practice has shown that a combination of belladonna alkaloids, ergotamine tartrate, and phenobarbitone (Bellergal) was effective in treating troublesome symptoms of the premenstrual syndrome of which fatigue, tender breasts, nervousness, irritability, lethargy and listlessness were improved to a statistically significant degree. The drug was given three times daily and caused no side effects.

Adolescent↗
PubMed1969

Reversal by pronethalol of dibenamine blockade: a study on the seminal vesicle of the guinea-pig.

1. The guinea-pig seminal vesicle has been shown to be a very suitable test object for the study of mechanisms involving alpha-adrenoceptive receptors, because no beta-receptors were found in this preparation.2. Adrenaline, noradrenaline and phenylephrine were directly acting agonists, their ED50 values being 7.1 x 10(-6)M, 1.5 x 10(-5)M and 2.7 x 10(-5)M, respectively.3. Pretreatment with reserpine had no influence on the contractions caused by adrenaline, noradrenaline and phenylephrine but abolished or greatly reduced the contractions caused by dopamine. Cocaine enhanced the effects of adrenaline, noradrenaline and phenylephrine and reduced those of dopamine.4. Pronethalol (6.8 x 10(-5)M) reversed the alpha-receptor blockade by dibenamine, ergotamine and phentolamine of responses to adrenaline, noradrenaline and phenylephrine; it did not affect the blockade by dibenamine of responses to histamine.5. Reversal of the blockade by dibenamine was observed only when its concentration was such that it caused a parallel shift of the dose-effect curves of the agonists to the right; higher concentrations, which caused an unsurmountable depression of the maximal contraction, were not antagonized by pronethalol.6. It is assumed that the reversal is dependent on a direct action on alpha-receptors, "spare receptors" being probably involved.

Animals↗
PubMed1989

Longterm prognosis of analgesic withdrawal in patients with drug-induced headaches.

We studied long-term prognosis and prognostic variables for therapeutic outcome of analgesic withdrawal in 54 patients with drug-induced headaches. The duration of headache history was 21.9 +/- 12.8 years. Each patient took an average of 38.8 +/- 22.8 tablets or suppositories a week and an average of 2.5 distinct drugs. Most patients used drugs containing several components. Caffeine was contained in at least one drug in all cases, ergotamine in 80.0% and pyrazolone in 77.1%. All patients were admitted to the hospital for two weeks. The analgesics were discontinued abruptly and the withdrawal symptoms were alleviated by neuroleptics and neurotropics. During the second week of hospital stay we started a basic therapy with calcium antagonists or beta blockers in patients suffering from migraine initially and with tricyclic antidepressants, physical therapy or biofeedback in patients suffering from tension type headaches initially. At the end of the study (mean follow-up period = 16.8 +/- 13.6 months) 38 patients (70.1%) were evaluated. 76.3% of these patients had significantly reduced their analgesic intake, 60.5% had experienced a significant relief of headache both in intensity and frequency, and 23.7% were therapeutic failures. Analysis of the time course of relapse revealed the first six months after hospital discharge as the critical period determining long-term success. The variables tested for prognostic relevance (age, sex, duration of headache history, number of tablets or suppositories taken a week, organic mental syndrome, and type of initial headaches) were not statistically significant.

Adult↗
PubMed1991

5-Hydroxtryptamine1D receptor agonism predicts antimigraine efficacy.

The interactions of four abortive anti-migraine agents and four prophylactic anti-migraine agents with 5-HT1D receptors in bovine brain were analyzed using radioligand binding techniques and adenylate cyclase assays. In bovine caudate, the affinities of abortive anti-migraine agents (i.e. 5-hydroxytryptamine, ergotamine, dihydroergotamine, sumatriptan) for 5-HT1D receptors range from 4.0-34 nM while the affinities of prophylactic anti-migraine agents (i.e. methysergide, amitriptyline, (-)propranolol, verapamil) range from 46-11,000 nM. In adenylate cyclase studies in bovine substantia nigra, all four abortive anti-migraine agents dose-dependently inhibit forskolin-stimulated adenylate cyclase activity, a biochemical effect mediated by 5-HT1D receptors. No agonist effect on cyclase activity is observed with the four prophylactic anti-migraine agents. These data support the hypothesis that abortive anti-migraine agents are 5-HT1D receptor agonists and that this effect may underlie their anti-migraine efficacy.

Adenylyl Cyclase Inhibitors↗
PubMedDate not supplied

Wolff Award presentation 1993. Anti-migraine drug interactions with cloned human 5-hydroxytryptamine1 receptor subtypes.

Multiple 5-hydroxytryptamine (5-HT) receptors have been identified in humans. A subgroup of these receptors (designated 5-HT1 receptors) have been hypothesized to be involved in the mechanism of action of acute anti-migraine drugs. At present, this hypothesis cannot be tested directly in human tissues due to technical limitations. However, recent molecular biological advances have allowed for the development of assays employing cloned human 5-HT1 receptors expressed in cells by DNA transfection. This study analyzed the ability of ergotamine, dihydroergotamine, and 5-HT and sumatriptan to interact with the four known human 5-HT1 receptor subtypes. The four acute anti-migraine agents interacted with all 4 human 5-HT1 receptor subtypes with less than 1 microM affinity. However, drug affinities for the human 5-HT1B and 5-HT1D receptors correlate most closely with the rank order of clinical dosages used to treat a migraine attack. Therefore, these data indicate that human 5-HT1B and/or 5-HT1D receptors are likely to mediate the therapeutic efficacy of acute anti-migraine drugs.

Ergotamine↗
PubMed1994

Migraine treatment: the British perspective.

Migraine occurs in about 10% of the population in the United States and the United Kingdom. In the United States there seem to be more complicated patients and the expectations of the patient are higher. In the United Kingdom there is a tendency to use single rather than compound formulations, and drugs such as barbiturates cannot be prescribed for migraine. In treating migraine the first and most important thing is to get the correct diagnosis which depends on the history and the absence of abnormal physical signs. Investigations do not confirm the diagnosis of migraine, they are only necessary to exclude other causes of headaches. Most sufferers from migraine have less than four attacks a month. Attack therapy is usually all that is required, and over the past 20 years efficient attack therapy has been developed. This depends mainly on sleep, an antinauseant, analgesics, ergotamine and more recently sumatriptan.

Acute Disease↗
PubMedDate not supplied

Denial of hospitalization by insurers for inpatient treatment of medication rebound headaches.

Inpatient treatment with intravenous dihydroergotamine has been remarkably successful in managing chronic daily headaches due to excessive use of analgesics or ergotamine tartrate. Recently we have been denied authorization in appropriate patients for this procedure by third party payers on the grounds that it was "not medically necessary," "based on anecdotal information," or is "an outpatient procedure." Three cases are described in which the insurer's decision was either contested as an issue of substandard care, or the patient elected to pay for the procedure. The outcome in two cases was dramatically favorable, at least from the patient's and the physician's point of view. The third case is currently being appealed. Time and energy spent on combating the position of the third party payer on issues of standards of specialist care should be unnecessary. Publication of standards of care by specialists, and a requirement that these care standards must be provided by third party payers are needed in order that quality medical care can continue in this society.

Analgesics↗