Ergot Derivatives Research Articles

Rizatriptan 10‐mg Wafer Versus Usual Nontriptan Therapy for Migraine: Analysis of Return to Function and Patient Preference

More than half of patients with migraine suffer moderate to severe functional disability during migraine attacks. To compare effects on functional disability at 2 hours after treating a migraine with rizatriptan 10-mg wafer versus usual nontriptan therapy for triptan-naïve patients with migraine. Open-label, prospective, two-attack study conducted at 111 neurology clinics. Adult patients with migraine treated two migraine attacks, the first with their usual nontriptan therapy (nonsteroidal anti-inflammatory drugs, 57%; analgesics, 27%; or ergot derivatives, 16%) and the second with rizatriptan 10-mg wafer. Patients recorded pain intensity and functional disability at the start, and functional disability at 2 hours, as well as the time of return to normal function. A total of 1353 patients, 76% of them female, completed the study and were considered evaluable. During first and second migraine attacks, 55% and 63% of patients, respectively, reported severe disability or requiring bed rest. At 2 hours after treatment, the likelihood of experiencing any disability was more than five times greater after usual nontriptan therapy than after rizatriptan (odds ratio, 5.68; 95% confidence interval (CI), 4.66 to 6.94; P < .001). Rizatriptan was twice as likely to return patients to normal function than usual nontriptan therapy after adjusting for confounding factors (adjusted hazard ratio, 2.08; 95% CI, 1.92 to 2.25; P < .001). Assessed over all time points up to 6 hours, the speed of return to normal function was 52% faster after rizatriptan therapy (P < .001). Significantly more patients preferred rizatriptan than usual nontriptan therapy (78.8% vs. 21.2%; P < .001). The most common reasons cited for preference for rizatriptan were faster relief of headache pain and faster return to normal function. Patients in this study were more likely to experience a return to normal function at 2 hours after receiving rizatriptan than after their usual nontriptan therapy for migraine. The results of this study, using patient-oriented, clinically relevant endpoints such as functional disability and preference, will help to guide practitioners in making recommendations for acute migraine treatment.

The Use of High-Dose Daily Cabergoline in an Adolescent Patient With Macroprolactinoma

Prolactinomas are rare in children and adolescents but well studied in adults. Dopamine agonists are the treatment of choice for all ages. Bromocriptine is the only agonist approved for use in pediatric patients by the FDA. Cabergoline, a second-generation ergot derivative with a longer half-life, has been used in resistant prolactinomas and as first-line treatment in adults. The authors describe an adolescent boy with a pituitary macroadenoma with an initial prolactin level of 73,777 ng/mL. After failing to respond to bromocriptine and standard-dose cabergoline, he responded well to very high daily doses of cabergoline (1.5 mg daily), with a current prolactin level of 726 ng/mL and notable reduction in tumor size. Escalating doses of cabergoline should be considered in pediatric patients with dopamine-resistant prolactinomas.

An Autopsy Case of Postpartum Acute Myocardial Infarction Associated with Postpartum Ergot Alkaloids Administration in Old-Aged Pregnant Women

Cases of acute myocardial infarction (AMI) that occur during pregnancy or postpartum are rarely reported. Ergot derivatives are known to induce the spasmodic contraction of coronary arteries. Administration of ergot derivatives can cause AMI, even in normal healthy people. In several reported cases, ergot derivatives triggered severe AMI during the postpartum period. Here, we report the case of a forty-year-old woman who was successfully impregnated by artificial fertilization and died after treatment with ergot derivatives. The autopsy revealed AMI with severe coronary atherosclerosis. This is the first case that reports aggravation of pre-existent severe coronary atherosclerosis after postpartum infusion of ergot derivtives.

Pharmacological treatment of attacks in juvenile migraine

Although migraine is a common complaint in childhood and adolescence, there is a lack of controlled clinical studies regarding treatment. In the young patient, the pharmacological approach should be preceded by setting up non-pharmacological measures which include behavioural intervention. The sole use of symptomatic therapies should be limited to patients who complain of up to four partially or totally disabling attacks, or those who suffer from headache for more than 4 days per month. The therapeutic armamentarium includes non-specific symptomatic drugs, such as analgesics and non-steroidal anti-inflammatory drugs (NSAIDs), as well as anti-emetics and specific drugs, such as the triptans. Analgesics and NSAIDs are the most frequently used drugs in childhood and adolescence for the symptomatic treatment of migraine attacks of slight or moderate intensity. The first-choice drug for those under 12 years of age is acetaminophen. Among NSAIDs, two double-blind, randomized, placebo-controlled studies were conducted for ibuprofen, supporting its efficacy. In the past, ergot derivatives played an important role in the treatment of spontaneous migraine attacks, particularly in adults, but after the triptan revolution their role was strongly confined to a small number of patients. Although they are considered first-choice drugs for moderate and severe migraine attacks in adults, triptans are still under study in migraine patients under 18 years of age. The Health Ministry rules do not approve their use in patients under 18 years. They can only be given legally if the therapeutic plan for their use is previously approved by the Ethics Committee and after informed consent from the patient/parents. Promising results have been obtained, particularly for sumatriptan in nasal spray formulation as well as for zolmitriptan and rizatriptan, showing a high tolerability and safety profile.

Fragmentation patterns of selected ergot alkaloids by electrospray ionization tandem quadrupole mass spectrometry.

Tall fescue toxicosis and other maladies in livestock result from the ingestion of vasoconstrictive ergot alkaloids produced by fungal endophytes associated symbiotically with the grass. In order to facilitate future analyses of grass extracts considered responsible for outbreak of related livestock diseases, we examined the electrospray ionization mass spectra of specific ergot alkaloids under conditions that permit protonation. Our purposes were both to record the spectra with interpretation of mechanisms of fragmentation and to derive commonalities that would allow the prediction of mass spectra of related compounds for which standards were not readily available. With [M + H](+) values in parentheses, water-insoluble lysergic acid peptide ergot derivatives ergovaline (m/z 534), ergotamine (m/z 582), ergocornine (m/z 562), ergocryptine (m/z 576) and ergocrystine (m/z 610) exhibited a consistent loss of water (-18 u) from the C-12' alpha-hydroxy functionality. Of this group, ergovaline and ergotamine generated an m/z 320 fragment deriving from cleavage of ring E amide and ether functions with retention of the peptide ring system methyl group. Ergocornine, ergocryptine and ergocrystine similarly formed an m/z 348 fragment with retention of isopropyl. These assignments were supported by the lack of similar fragments from the water-soluble ergot ergonovine, which lacks a peptide ring system. Clavine-type ergot alkaloids lysergic acid and lysergol lack any substituents beyond simple ones directly on the C-8 position and, similarly to ergonovine, lack significant fragments at m/z 268, 251 and 225 shared by the peptide ergot alkaloids.

Allergie aux triptans

Triptans are remarkably effective treatment for migraine attacks. The most frequent adverse effects are a feeling of thoracic pressure or of tightness, dizziness, tingling and flushes. Clinically patent coronary artery manifestations and allergic manifestations are exceptional with these products. Here we report two cases of urticaria due to triptans: one to sumatriptan, the second to naratriptan and eletriptan. Prick tests with a solution of sumatriptan were positive in both patients. Six healthy control subjects and five patients with a history of migraine attacks who were being treated with a triptan but who had no evidence of triptan-induced clinical allergy were prick test-negative to these drugs. We conclude that the skin tests demonstrate cross-reactivity between triptans, reflecting the similarity of their chemical structures. Cross reactivity was not observed between ergot derivatives and triptans.

Pergolide mesylate form II

A new polymorph of pergolide mesylate or 8beta-[(methylsulfanyl)methyl]-6-propylergoline methanesulfonate, C(19)H(27)N(2)S(+).CH(3)SO(3)(-), is reported. Pergolide mesylate form II crystallizes in the trigonal system, which is unique for ergot derivatives. Although the hydrogen-bond system in form II differs completely from that in form I, the conformation of the pergolide moiety in various related structures is very similar.

Migraine treatment patterns and patient satisfaction with prior therapy: A substudy of a multicenter trial of rizatriptan effectiveness

Background: Migraine is a common, chronic, often disabling neurologic condition that is underdiagnosed and undertreated. Objective: We undertook this questionnaire-based study as a substudy of a multicenter trial of rizatriptan effectiveness. Our goal was to assess the history of acute migraine medication use and the relationship between different migraine medication regimens and patient satisfaction with prior therapy. Methods: This study was conducted at 85 neurology clinics throughout Spain from March Lo December 2001. It was planned prospectively as part of the screening visit for a multicenter trial of the effectiveness of rizatriptan therapy for migraine. Male and female patients ≥18 years of age were eligible for the primary trial, and hence for this study, if they had a history of migraine attacks and did not have a contraindication for triptan use. At the screening visit for the primary trial, a questionnaire was used by clinicians to record past and current use, and duration and order of use, of analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), ergot derivatives, and triptans; satisfaction with treatment was scored on a 5-point scale ranging from “very dissatisfied” to “very satisfied.” Results: Of 712 patients completing the questionnaire (mean [SD] age, 34 [10] years; range, 18–69 years), 75% were women and 94% experienced moderate or severe functional disability during migraine attacks. Analgesics were used by the majority of patients (81%) and for the longest mean [SD] duration (8.8 [7.6] years) but were associated with the least satisfaction (10% of patients “very satisfied” or “somewhat satisfied”). Triptans were used by the fewest patients (32%) and for the shortest mean duration (18 [1.6] years) but were associated with the highest rate of satisfaction (66%) compared with NSAIDs (27%) and ergot derivatives (31%). Regardless of duration or order of drug use, or sex or age of the patient, the likelihood of satisfaction with triptans was significantly greater ( P < 0.001) than with nontriptan regimens, with an adjusted odds ratio (95% CI) of 16.8 (11.4–24.9) versus analgesics, 5.1 (3.6–7.1) versus NSAIDs, and 4.1 (2.8–6.0) versus ergot derivatives. Conclusions: Our results showed that analgesics, NSAIDs, and ergot derivatives were used for long durations but provided low satisfaction among patients. Triptans were rarely used as a first treatment choice; however, patients reported the highest treatment satisfaction scores after triptan therapy compared with ergot derivatives, NSAIDs, or analgesics.

Prise en charge d’une crise migraineuse rebelle chez l’adulte

The management of intractable migraine is not yet standardised. The first point in the emergency department is to eliminate severe cephalalgic non-migrainous disease, then to confirm the diagnosis of migraine. The second point is to determine trigger factors responsible for the refractory migraine – principally inadequate therapy, such as too low a dosage, inadequate treatment compared with intensity, and delayed treatment. Examples of inadequate classical treatments are presented for the following four main oral therapies: a nonsteroidal anti-inflammatory drug (NSAID), analgesics, ergot derivatives, and triptans. When these drugs are ineffective, the following are used via injections: propacetamol, aspirin (lysine acetylsalicylate), injectable NSAIDs, and nefopam. These products differ from country-to-country. For example, morphinomimetics, phenothiazines and corticosteroids are widely prescribed in the US, while metamizole (dipyrone) is preferred in developing countries. The authors describe the different modes of administration and the adverse effects of the substances. Finally, they describe the treatment of status migrainosus. Globally, triptans are underused in emergency departments. This review confirms the need for controlled trials of treatments for migraine in emergency departments in order to develop an international therapeutic consensus.

Dihydroergocriptine in Parkinson's disease: clinical efficacy and comparison with other dopamine agonists.

The present paper reviews clinical studies on the use of dihydroergocriptine (DHEC), an ergot derivative with dopamine agonist activity, for the treatment of Parkinson's disease. This compound is a hydrogenated ergot derivative structurally quite similar to bromocriptine, from which it differs because of the hydrogenation in C9 C10 and the lack of bromine in C2. DHEC has a potent D2-like receptor agonist and a partial D1-like receptor agonist activity; because of this biochemical profile, it has been suggested that DHEC may produce fewer side-effects and have clinical efficacy equal to that of a classical dopamine agonist. Several open-label and double-blind studies indicate that DHEC is an efficacious remedy for parkinsonian signs and symptoms. Further studies are necessary to compare DHEC to new dopamine agonists (pergolide, cabergoline, ropinirole, and pramipexole) which have been more recently marketed.

Overuse of symptomatic medications among chronic (transformed) migraine patients: profile of drug consumption.

Chronic daily headache and chronic (transformed) migraine (TM) patients represent more than one third of the subjects seen in specialized headache centers. Most of these patients may overuse symptomatic medications (SM) taken on a daily basis to relieve headache and associated symptoms. The conversion to the daily or near-daily pattern of headache presentation is thought to be related to the medication overuse. The aim of this study was to evaluate the profile of SM consumption among transformed migraine patients attending a tertiary center. One hundred thirty three consecutive patients (22 men and 111 women, ages 17 to 80) with TM and overuse of SM according to the proposed criteria of Silberstein et al (1994, 1996) were prospectively studied. None of the patients were under treatment for other conditions. Among them, 73 (54.9%) were using one category of SM, while 55 (41.3%) and 5 (3.8%) patients were taking simultaneously two and three categories of SM respectively. The categories of overused symptomatic medications varied from simple analgesics to narcotics, triptans and combinations of ergot derivatives and caffeine and of analgesics and caffeine. The average intake per patient per day was of 3 to 4 tablets and mostly of the patients overused simple analgesics (isolated or in combination with other substances) (75.2%), caffeine containing drugs (71.4%), drugs containing ergotamine derivatives (26.1%), triptans (alone or combined) (15.5%), drugs with narcotics or ansiolitics (13%) and anti-inflammatory drugs (3.7%). The mechanisms by which the overuse of symptomatic medications may play a role in this transformation are uncertain but despite of the necessity of controlled trials to demonstrate the real role of such compounds in the development of transformed migraine, this study emphasizes the necessity for more rigorous prescribing guidelines for patients with frequent headaches.

Lopinavir/ritonavir: a review of its use in the management of HIV infection.

Lopinavir/ritonavir: a review of its use in the management of HIV infection.

Abortifacient and endocrine effects of metergoline in beagle bitches during the second half of gestation

The purpose of this study was to investigate the abortifacient effects of high doses of metergoline when administered to pregnant beagle bitches during the second half of gestation and to define the endocrine effects of this treatment as represented by plasma progesterone and estradiol concentrations. Previously, metergoline had been shown to be incompletely luteolytic and induced abortion in only one of eight pregnant bitches when 0.4–0.5 mg/kg were administered twice daily for 5 days from Days 18 to 20 of diestrus. Nine pregnancies in six beagle bitches were used for the present study. Three bitches were treated in each of two consecutive pregnant cycles. Metergoline was administered at a dose of 0.6 mg/kg per os twice daily, starting on Day 28 after the cytological onset of diestrus. Abortion was induced in eight of the nine treated pregnancies and started after 3–23 days of treatment (mean 12.5 days, S.D. 6.4 days). The abortions were completed within 0.5–8 days (mean 2.2 days, S.D. 2.7 days). There were no side effects associated with metergoline treatment and none of the abortions was associated with complications that required intervention. In the single bitch that did not abort, an ovarian granulosa cell tumor was discovered when the single fetus had to be removed surgically at term. Plasma progesterone concentrations declined after the start of metergoline administration in all pregnancies but levels below 4.8 nmol/l were required for successful abortions. Plasma estradiol concentrations showed a tendency to decline and fluctuate concurrently with the plasma progesterone levels. However, suppression of plasma estradiol concentrations by metergoline was not as complete as the suppression of progesterone and did not seem a prerequisite for abortion. The hormone profiles and treatment period required for abortion tended to be similar for both cycles of the three bitches that were treated during two consecutive pregnancies. This suggests a bitch effect on the factors that determine the efficacy of metergoline to induce abortion. The large variation and length of the treatment period that was required until abortion commenced was probably related to the relatively early start of treatment compared to other studies. The results of this investigation suggest that, similar to other prolactin suppressing ergot derivatives, metergoline causes complete luteolysis and can be used to reliably induce abortion only during the last 3 weeks of gestation.

Managing Ergot-Induced Gangrene: The Anesthesiologist as a Key Player

Managing Ergot-Induced Gangrene: The Anesthesiologist as a Key Player

DA agonists -- ergot derivatives: dihydroergocryptine (DHEC): management of Parkinson's disease.

DA agonists -- ergot derivatives: dihydroergocryptine (DHEC): management of Parkinson's disease.

Effects of topical natural ergot alkaloids on intraocular pressure and aqueous humor dynamics in ocular normotensive rabbits.

Although it has been suggested that ergot derivatives may play a role in antiglaucoma therapy, little attention has been paid to the ocular hypotensive action of these drugs. Having previously reported in our laboratory that topical dihydroergocristine decreases intraocular pressure both in ocular normotensive and alpha-chymotrypsin-induced ocular hypertensive rabbits, the aim of the present work was to assess the effect of natural ergot alkaloids, ergocristine, alpha-ergocryptine and ergocornine, on the intraocular pressure and aqueous humor dynamics in ocular normotensive rabbits in order to further explore the ocular actions of these compounds. Intraocular pressure was measured with a pneumatonometer manometrically calibrated for the rabbit eye. Changes in tonographic facility of aqueous humor outflow and rate of aqueous humor inflow were evaluated in anesthetized rabbits. Natural ergot alkaloids were found to reduce intraocular pressure in ocular normotensive eyes in a dose-related fashion. These compounds decreased both tonographic outflow facility and, to a greater extent, aqueous humor inflow, which explains their final hypotensive effect.

Respiratory Complications of Parkinson's Disease

Patients with Parkinson's disease are at risk for pulmonary complications as a consequence of both the underlying disease pathology and the side effects of medication. Degeneration of the substantia nigra and subsequent loss of dopaminergic neurons may produce changes in ventilatory parameters. Upper airway obstruction and chest wall restriction are both common, and both may respond to levodopa. However, therapy for Parkinson's may also contribute to pulmonary morbidity. Overtreatment with levodopa causes respiratory dyskinesia that may be difficult to differentiate from complications of the disease itself. Therapy with ergot derivatives may cause pleuropulmonary fibrosis. Pneumonia resulting from the respiratory complications remains a significant cause of morbidity and mortality in Parkinson's disease.

Clinical Pharmacokinetic and Pharmacodynamic Properties of Drugs Used in the Treatment of Parkinson??s Disease

Current research in Parkinson's disease (PD) focuses on symptomatic therapy and neuroprotective interventions. Drugs that have been used for symptomatic therapy are levodopa, usually combined with a peripheral decarboxylase inhibitor, synthetic dopamine receptor agonists, centrally-acting antimuscarinic drugs, amantadine, monoamine oxidase-B (MAO-B) inhibitors and catechol-O-methyltransferase (COMT) inhibitors. Drugs for which there is at least some evidence for neuroprotective effect are certain dopamine agonists, amantadine and MAO-B inhibitors (selegiline). Levodopa remains the most effective drug for the treatment of PD. Several factors contribute to the complex clinical pharmacokinetics of levodopa: erratic absorption, short half-life, peripheral O-methylation and facilitated transport across the blood-brain barrier. In patients with response fluctuations to levodopa, the concentration-effect curve becomes steeper and shifts to the right compared with patients with stable response. Pharmacokinetic-pharmacodynamic modelling can affect decisions regarding therapeutic strategies. The dopamine agonists include ergot derivatives (bromocriptine, pergolide, lisuride and cabergoline), non-ergoline derivatives (pramipexole, ropinirole and piribedil) and apomorphine. Most dopamine agonists have their specific pharmacological profile. They are used in monotherapy and as an adjunct to levodopa in early and advanced PD. Few pharmacokinetic and pharmacodynamic data are available regarding centrally acting antimuscarinic drugs. They are characterised by rapid absorption after oral intake, large volume of distribution and low clearance relative to hepatic blood flow, with extensive metabolism. The mechanism of action of amantadine remains elusive. It is well absorbed and widely distributed. Since elimination is primarily by renal clearance, accumulation of the drug can occur in patients with renal dysfunction and dosage reduction must be envisaged. The COMT inhibitors entacapone and tolcapone dose-dependently inhibit the formation of the major metabolite of levodopa, 3-O-methyldopa, and improve the bioavailability and reduce the clearance of levodopa without significantly affecting its absorption. They are useful adjuncts to levodopa in patients with end-of-dose fluctuations. The MAO-B inhibitor selegiline may have a dual effect: reducing the catabolism of dopamine and limiting the formation of neurotoxic free radicals. The pharmacokinetics of selegiline are highly variable; it has low bioavailability and large volume of distribution. The oral clearance is many-fold higher than the hepatic blood flow and the drug is extensively metabolised into several metabolites, some of them being active. Despite the introduction of several new drugs to the antiparkinsonian armamentarium, no single best treatment exists for an individual patient with PD. Particularly in the advanced stage of the disease, treatment should be individually tailored.

A review of canine pseudocyesis.

The purpose of this article is to review the most relevant features of the physiology, clinical signs, diagnosis, treatment and prevention of canine pseudocyesis (PSC). This is a physiological syndrome, characterized by clinical signs such as: nesting, weight gain, mammary enlargement, lactation and maternal behaviour, which appears in non-pregnant bitches at the end of metaoestrus. PSC is a frequent finding in domestic dogs. Although it is generally admitted that prolactin (PRL) plays a central role in the appearance of PSC, its precise aetiophysiology is not completely understood yet. A number of clinical studies suggest that at some point of metaoestrus circulating PRL levels rise in overtly pseudopregnant bitches. Individual differences in sensitivity to PRL as well as the existence of molecular variants of canine PRL with different bioactivity versus immunoreactivity ratios may help clarify the aetiopathology of PSC. Diagnosis of PSC is based on the presence of typical clinical signs in metaoestrous non-pregnant bitches. Considering that PSC is a self limiting physiological state, mild cases usually need no treatment. Discouraging maternal behaviour and sometimes fitting Elizabethan collars to prevent licking of the mammary glands may suffice in these cases. Sex steroids (oestrogens, progestins and androgens) have been traditionally used to treat PSC but the side-effects usually outweigh the benefits of these medications. Inhibition of PRL release by ergot derivatives [bromocriptine (10-100 microg/kg per day for 10-14 days], cabergoline (5 microg/kg per day during 5-10 days), metergoline (0.2 mg/kg per day during 8-10 days) has proved to be effective for the treatment of canine PSC. Although some of these ergot derivatives present some untoward side-effects, they are transient and can usually be managed. Predisposed bitches not intended for breeding should be spayed as ovariectomy is the only permanent preventive measure.

Efficacy of nicergoline in dementia and other age associated forms of cognitive impairment.

Efficacy of nicergoline in dementia and other age associated forms of cognitive impairment.