Ergotamine Research Articles

Efficacy, tolerability and safety of oral eletriptan and ergotamine plus caffeine (Cafergot) in the acute treatment of migraine: a multicentre, randomised, double‐blind, placebo‐controlled comparison.

Eur Neurol. 2002;47(2):99‐107The 5‐HT(1B/1D/1F) agonist eletriptan, at an oral dose of 80 mg, has been shown to be more efficacious than sumatriptan 100 mg and placebo in the treatment of migraine attacks with or without aura. Another commonly prescribed oral treatment for migraine attacks is Cafergot (1 mg ergotamine tartrate with 100 mg caffeine per tablet). The efficacy, tolerability and safety of 40‐ and 80‐mg doses of eletriptan and 2 tablets of Cafergot were compared in a double‐blind, randomised, placebo‐controlled, parallel‐group trial involving 733 migraine patients. Patients recorded symptoms at baseline (before treatment) and 1, 2, 4 and 24 h after dosing. Headache intensity was assessed on a 4‐point scale (3 = severe pain, 2 = moderate pain, 1 = mild pain, 0 = no pain). Significantly more eletriptan‐treated patients (80 mg, 68%; 40 mg, 54%) than Cafergot‐treated patients (33%; p < 0.001) reported headache response (improvement from moderate‐to‐severe to mild or no pain) at 2 h. Substantially more eletriptan recipients reported no pain (80 mg, 38%; 40 mg, 28%; Cafergot, 10%; placebo, 5%; p < 0.001). Eletriptan headache response rates at 1 h were significantly higher (80 mg, 39%; 40 mg, 29%; Cafergot, 13%; placebo, 13%; p < 0.002 for each comparison). Both doses of eletriptan were significantly more effective than Cafergot in reducing nausea (p < 0.0001), photophobia (80 mg, p < 0.0001; 40 mg, p < 0.002), phonophobia (80 mg, p < 0.0001; 40 mg, p < 0.003) and functional impairment (p < or = 0.001) at 2 h. Adverse events were generally mild or moderate and transient. This randomised trial shows that oral eletriptan is more efficacious in the acute treatment of migraine than oral Cafergot and is well tolerated.Comment: As with all comparative trials with eletriptan, this comparative trial raises the important issue of blinding. Was the Cafergot encapsulated (hence potentially hindering the early phase of absorbtion)? This approach has been a major issue with previous eletriptan studies and may potentially make the results from this trial difficult to interpret. DSM One key issue in ensuring methodologically rigorous comparative trials is symmetry of comparative groups. I have come to believe that the controversy over encapsulation for blinding is neither about the pharmacokinetics of encapsulation, nor about the effectiveness of eletriptan, but rather about the methodology of comparison, which requires as much symmetry as possible. As Gawel and Wiebe wrote in a superb article explaining how to critically evaluate a comparison trial, “When faced with a potential confounder … readers need to estimate in which direction the results would be biased” in any comparative trial (Gawel M, Wiebe S. Evidence‐based analysis of a migraine treatment drug comparison trial. Cephalalgia. 2000;20[suppl 2]:33‐38). SJT

Cluster headache: aetiology, diagnosis and management.

Drugs. 2002;62(1):61‐69Cluster headache is characterised by repeated attacks of strictly unilateral pain in the orbital region associated with local autonomic symptoms or signs. The attacks are brief but of a very severe, almost excruciating intensity. For unknown reasons males are affected more often than females. Recent studies suggest that an autosomal dominant gene has a role in some families with cluster headache. Hormonal studies indicate a dysfunction in the central nervous system. Neuroimaging has revealed primary defects in the hypothalamic grey matter. Local homolateral dilatation in the intracranial segment of the internal carotid and ophthalmic arteries during attacks is the result of a generic neurovascular activation, probably mediated by trigeminal parasympathetic reflexes. Sumatriptan 6mg subcutaneously is the drug of choice in the treatment of acute attacks. Inhalation of 100% oxygen can also be recommended. In the prophylactic treatment, verapamil is the first option. Other drugs that can be considered are corticosteroids, which may induce a remission of frequent, severe attacks, and lithium. Oral ergotamine tartrate may be sufficient for patients with night attacks and/or short, rather mild to moderately severe cluster headache periods. Third line drugs are serotonin inhibitors (methysergide and pizotifen) and valproic acid. Patients should be encouraged to keep headache diaries and be carefully instructed about the nature and treatment of the headaches. Alcohol can bring on extra attacks and should not be consumed during active periods of cluster headache.Comment: A useful review of clinical options. Given the effectiveness of injectable sumatriptan and the prophylactic use of ergotamine mentioned, one might speculate that the new intranasal formulations of triptans (eg, zolmitriptan) and triptans with a longer half‐life (eg, frovatriptan) may prove to be effective in the treatment of cluster headache. DSM

Antagonistic effects of simultaneous exposure of ergot alkaloids on kidney adenosine triphosphatase system.

Much of the research on fescue toxicosis has concentrated on evaluating animal response to grazing endophyte-infected (E+) versus endophyte-free tall fescue or the effects of single toxins such as ergonovine (EN), ergovaline (EV), or ergotamine (ET) on animal performance. Such approaches have eliminated the opportunity to test the possible additive, synergistic, or antagonistic interactions of one or more ergot alkaloids with the other ergot alkaloids found in E+ tall fescue. This study was conducted to determine the effects of simultaneous exposure of pairs of EN, EV, and ET on the kidney adenosine triphosphatase (ATPase) system in vitro. Tests were performed using three separate rat kidney homogenates and were repeated four times at concentrations of 0, 75, and 200 microM. Individually, EN, EV, and ET induced dose-dependent inhibitions of kidney Na(+)/K(+) ATPase, with EN being most potent, followed by purified EV, and then by ET. The ergot alkaloids inhibited Mg(2+) ATPase to a lesser degree than Na(+)/K(+) ATPase, with EN again being the most potent toxin. Simultaneous exposure to any combination of the ergot alkaloid pairs tested (EV + ET, EV + EN, and ET + EN) resulted in significant interactions (P < 0.05), indicating antagonistic effects on the inhibition of Na(+)/K(+) ATPase and Mg(2+) ATPase for most concentration combinations. These interactions suggest that in studies of the effects of any ergot alkaloid on animal performance, effects of other ergot alkaloids may also be present. Effects may not be additive, as was the case in this study, and the presence of one toxin may enhance or hinder the effectiveness of others.

Automated sequential injection fluorimetric determination and dissolution studies of Ergotamine Tartrate in pharmaceuticals

A fully automated flow system for drug-dissolution studies based on the sequential injection analysis (SIA) was described and used for monitoring dissolution profiles of Ergotamine Tartrate (ET) in pharmaceutical formulations. 50 μl of dissolution medium was taken for each measurement at a flow rate of 40 μl s −1 and detected by fluorescence detector using λ ex=236 nm ( λ em≥390 nm). The calibration curve was linear over the range 0.03–0.61 mg l −1 of ET (sufficient for the dissolution tests). Equation of the calibration curve was calculated giving the following values: F=117.7 c+0.80 ( n=6); r=0.9998. Detection limit was 0.01 mg l −1 of ET. The R.S.D. is less than 0.54 and 0.86% ( n=10) when determining 0.61 and 0.03 mg l −1 of ET in standard solution, respectively. The dissolution test of Bellaspon tablets (0.3 mg of ET in 1 tablet) was programmed for 20 min, with a continuous sampling rate of 120 h −1 under conditions required by BP 1993.

Patients May Need Treatment For Comorbid Migraines

Patients May Need Treatment For Comorbid Migraines

Buccal absorption of ergotamine tartrate using the bioadhesive tablet system in guinea-pigs

The buccal administration of ergotamine tartrate (ET) combined with polyvinyl alcohol (PVA) gel brought about higher plasma concentration of ET compared with that of oral administration of capsules in guinea-pigs. T max of ET in plasma of buccal administration was significantly smaller than that of oral administration. For the buccal dosage form of ET, the bioadhesive tablet system (BTS) was newly developed. It consisted of a reservoir of drug and an adhesive region. BTS showed better absorption of ET compared with PVA gel in guinea pigs. Among several pharmaceutical bases in the reservoir of BTS, Witepsol W-35 was most effective. It is likely that the high lipophilic property of Witepsol W-35 in which ET was dissolved facilitated the drug release by its relatively low melting point (around 35 °C), consequently a rapid absorption. In addition, the enhancing activity of the cod-liver oil extract (CLOE) in hydrophilic ointment on the in vivo buccal ET absorption was clarified to be comparable to that in the in vitro study utilizing the keratinized epithelial-free membrane (KEF-membrane) of the hamster cheek pouch.

Ergotamine-induced anorectal strictures: report of five cases.

Ergotamine tartrate suppositories are used for treatment of migraine headache attacks. Chronic abuse may lead to severe anorectal complications such as ulceration, stricture, and rectovaginal fistula. These complications are rare, and only sporadic reports may be found. Nevertheless, awareness of this entity on the part of prescribing physicians and treating colorectal surgeons is essential for a successful outcome, because withdrawal of this medication is an inherent part of treatment. Five female patients were referred for treatment of symptomatic strictures of the anal canal and lower rectum. All of these patients admitted prolonged, nearly daily use of three to seven ergotamine tartrate suppositories. Three patients with severe stenosis of the anal verge and anal canal were treated by Y-V anoplasty, and two patients with circular stricture of the lower third of the rectum had balloon dilatations. In all patients the use of ergotamine suppositories was stopped, and alternative medication was instituted. Long-term follow-up (3-12 years) showed complete resolution of symptoms. In view of the availability of new effective drugs for treatment of migraine headache (serotonin agonists) and considering the potentially severe complications of chronic use of ergotamine, the use of this medication should be abandoned.

Efficacy, Tolerability and Safety of Oral Eletriptan and Ergotamine plus Caffeine (Cafergot®) in the Acute Treatment of Migraine: A Multicentre, Randomised, Double-Blind, Placebo-Controlled Comparison

The 5-HT_1B/1D/1F agonist eletriptan, at an oral dose of 80 mg, has been shown to be more efficacious than sumatriptan 100 mg and placebo in the treatment of migraine attacks with or without aura. Another commonly prescribed oral treatment for migraine attacks is Cafergot^® (1 mg ergotamine tartrate with 100 mg caffeine per tablet). The efficacy, tolerability and safety of 40- and 80-mg doses of eletriptan and 2 tablets of Cafergot^® were compared in a double-blind, randomised, placebo-controlled, parallel-group trial involving 733 migraine patients. Patients recorded symptoms at baseline (before treatment) and 1, 2, 4 and 24 h after dosing. Headache intensity was assessed on a 4-point scale (3 = severe pain, 2 = moderate pain, 1 = mild pain, 0 = no pain). Significantly more eletriptan-treated patients (80 mg, 68%; 40 mg, 54%) than Cafergot-treated patients (33%; p < 0.001) reported headache response (improvement from moderate-to-severe to mild or no pain) at 2 h. Substantially more eletriptan recipients reported no pain (80 mg, 38%; 40 mg, 28%; Cafergot, 10%; placebo, 5%; p < 0.001). Eletriptan headache response rates at 1 h were significantly higher (80 mg, 39%; 40 mg, 29%; Cafergot, 13%; placebo, 13%; p < 0.002 for each comparison). Both doses of eletriptan were significantly more effective than Cafergot in reducing nausea (p < 0.0001), photophobia (80 mg, p < 0.0001; 40 mg, p < 0.002), phonophobia (80 mg, p < 0.0001; 40 mg, p < 0.003) and functional impairment (p ≤ 0.001) at 2 h. Adverse events were generally mild or moderate and transient. This randomised trial shows that oral eletriptan is more efficacious in the acute treatment of migraine than oral Cafergot and is well tolerated.

Cluster headache: aetiology, diagnosis and management.

Cluster headache is characterised by repeated attacks of strictly unilateral pain in the orbital region associated with local autonomic symptoms or signs. The attacks are brief but of a very severe, almost excruciating intensity. For unknown reasons males are affected more often than females. Recent studies suggest that an autosomal dominant gene has a role in some families with cluster headache. Hormonal studies indicate a dysfunction in the central nervous system. Neuroimaging has revealed primary defects in the hypothalamic grey matter. Local homolateral dilatation in the intracranial segment of the internal carotid and ophthalmic arteries during attacks is the result of a generic neurovascular activation, probably mediated by trigeminal parasympathetic reflexes. Sumatriptan 6mg subcutaneously is the drug of choice in the treatment of acute attacks. Inhalation of 100% oxygen can also be recommended. In the prophylactic treatment, verapamil is the first option. Other drugs that can be considered are corticosteroids, which may induce a remission of frequent, severe attacks, and lithium. Oral ergotamine tartrate may be sufficient for patients with night attacks and/or short, rather mild to moderately severe cluster headache periods. Third line drugs are serotonin inhibitors (methysergide and pizotifen) and valproic acid. Patients should be encouraged to keep headache diaries and be carefully instructed about the nature and treatment of the headaches. Alcohol can bring on extra attacks and should not be consumed during active periods of cluster headache.

Ergotamine and sumatriptan prescribing in The Netherlands

Ergotamine and sumatriptan prescribing in The Netherlands

Ergotamine and sumatriptan prescribing in The Netherlands

Ergotamine and sumatriptan prescribing in The Netherlands

Effect of an acute ergotamine challenge on reproductive hormones in follicular phase heifers and progestin-treated cows

The objective of this research was to determine if ergotamine, an ergopeptine alkaloid isolated from Neotyphodium-infected grasses and associated with toxicoses in livestock, altered plasma concentrations of reproductive hormones in follicular phase heifers and in cows given a progestin implant. In Experiment 1, blood was sampled for 8 h from four cycling heifers 2 days after synchronized luteolysis. Heifers were treated with ergotamine tartrate (19 μg/kg) i.v. or saline vehicle in a simple cross-over design after 1 h of pre-treatment blood sampling. Heifers received oxytocin (100 USP units) i.v. 4 h after ergotamine or saline treatment. Ergotamine reduced ( P<0.01) prolactin concentrations from 1 to 4 h post-treatment and increased ( P<0.01) 13,14-dihydro-15-keto prostaglandin F 2α (PGFM) concentrations from 2 to 5 h post-treatment. A PGFM response to oxytocin was not detected. In Experiment 2, blood was sampled for 8 h from six cycling cows 10 days after receiving a s.c. norgestomet implant. Cows were treated i.v. with ergotamine (20 μg/kg) or saline in a simple cross-over design after 1 h of pre-treatment blood sampling. Cows received gonadorelin (GnRH, 100 μg) i.v. 1 h after ergotamine or saline. Cows received oxytocin (100 USP units) i.v. 4 h after ergotamine or saline treatment. Ergotamine reduced ( P<0.01) serum prolactin concentrations by 120 min after treatment, with prolactin returning to pre-treatment concentrations by 200 min after treatment. Saline-treated cows had lower ( P<0.01) prolactin by 280 min after treatment. Ergotamine-treated cows had higher ( P<0.01) PGFM concentrations compared to saline-treated cows 120–240 min after treatments, but the groups exhibited similar increases in PGFM after oxytocin. Plasma LH and FSH concentrations increased to peaks 100–120 min after GnRH for both groups. However, the LH response to GnRH was greater ( P<0.01) for ergotamine-treated cows. In summary, ergotamine lowered prolactin and elevated PGFM concentrations in follicular phase heifers and cows on norgestomet therapy. Ergotamine increased the LH response to exogenous GnRH in cows with norgestomet implants. These data highlight the potential of ergopeptine alkaloids to affect reproduction through altered endocrine function.

Comparison of the effectiveness of eletriptan, sumatriptan and Cafergot® in reducing the time loss associated with migraine attacks

This study compared the effectiveness of different treatments for migraine in reducing the time loss caused by attacks. Two dosage strengths of eletriptan (40 mg and 80 mg) were compared with Cafergot® (2 mg ergotamine tartrate plus 200 mg caffeine) and with sumatriptan (50 mg and 100 mg) and placebo. Total Time Loss and Work Time Loss (including reduced effectiveness whilst continuing to work during attacks as well as absenteeism) were determined from patient questionnaires. Eletriptan at doses of 40 or 80 mg led to a statistically significant reduction in Total Time Loss compared with placebo. There was also a statistically significant reduction for both eletriptan doses compared with Cafergot®. For Work Time Loss, both doses of eletriptan were superior to placebo and the 80 mg dose of eletriptan was superior to Cafergot®. The differences in Total and Work Time Loss between eletriptan and sumatriptan were not statistically significant.Cafergot®is a registered trademark of Alliance Pharmaceuticals, UK.

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.

Rôles d'une dysplasie artérielle, d'un ergotisme chronique et d'autres facteurs dans un cas de dissections artérielles multiples spontanées

Spontaneous dissection of cervical and visceral arteries are rare and usually associated with an underlying arterial disease. The authors report the unusual case of a 50-year-old woman with high blood pressure who presented spontaneous dissection of cervico-cephalic, renal and hepatic arteries and of the descending aorta. She had been taking ergotamine tartrate for ten years for migraine. She also suffered from Raynaud's syndrome worsened by treatment. The respective roles of arterial dysplasia, chronic ergotism, renovascular hypertension and migraine are discussed.

Physiological responses of Brahman and Hereford steers to an acute ergotamine challenge.

Research was conducted to evaluate the sensitivity of Bos indicus and Bos taurus cattle to a tall fescue ergopeptine alkaloid by assessing vital sign responses. Eight Polled Hereford and seven Red Brahman steers received bolus i.v. injections of ergotamine tartrate and saline vehicle in a simple cross-over design. Physiological traits measured 30 min and immediately before and 30, 60, and 90 min after treatment were respiration rate, rectal temperature, skin temperature at the tailhead and tail tip, systolic and diastolic blood pressure, and heart rate. Blood samples were collected immediately before and 105 min after treatments to determine plasma prolactin and cortisol concentrations. Steers were fed a fescue-free diet in drylot. Ambient temperature and relative humidity averaged 31 degrees C and 55%, respectively, during data collection. No breed x treatment x time interactions were apparent for vital signs. The treatment x time interaction was significant (P < .05) for blood pressure and skin temperature. Ergotamine increased (P < .01) blood pressure and decreased (P < .01) skin temperature. The breed x treatment x time interactions were significant for prolactin (P < .1) and cortisol (P < .01). Ergotamine decreased plasma (P < .01) prolactin and increased (P < .01) cortisol concentrations in both breeds, despite some breed variation. Across all traits, Brahman and Hereford steers responded similarly to acute ergotamine exposure, indicating that the breeds are alike in acute sensitivity to a systemically administered ergopeptine alkaloid associated with fescue toxicosis.

Ergotamine alters plasma concentrations of glucagon, insulin, cortisol, and triiodothyronine in cows.

Bovine plasma was assayed to determine whether ergotamine, an ergopeptide isolated from endophytic tall fescue, affected cortisol, triiodothyronine, insulin, and glucagon concentrations. In Exp. 1, four heifers received an i.v. bolus injection of ergotamine tartrate (19 microg/kg BW) or saline vehicle in a simple crossover design 2 d after induced luteolysis. Oxytocin (100 USP units) was i.v. administered 4 h after ergotamine or saline. Treatment x time affected (P < .01) respiration rates and plasma concentrations of cortisol, triiodothyronine, insulin, and glucagon. Respiration rates were elevated (P < .01) 2 to 7 h after ergotamine, but they were unchanged after saline. Plasma cortisol concentrations were increased (P < .01) 1 to 3 h after ergotamine but not after saline. Plasma triiodothyronine was elevated 2 h after ergotamine, but it was unchanged in response to saline. Insulin decreased (P < .01) and glucagon increased (P < .01) during the 1st h after ergotamine, but not in response to saline. A second increase (P < .01) of glucagon was observed 3 h after ergotamine. In Exp. 2, six cows were treated with an i.v. bolus injection of ergotamine (20 microg/kg BW) or saline in a simple crossover design 10 d after receiving a s.c. ear implant containing norgestomet. Oxytocin (100 USP units) was i.v. administered 4 h after ergotamine or saline. Treatment x time affected (P < .001) respiration rates, cortisol, insulin, and glucagon and tended to influence (P = .12) triiodothyronine concentrations. Respiration rates were elevated (P < .01) 1 to 7 h after ergotamine but were unaltered by saline. Plasma cortisol was elevated (P < .01) 1 to 5 h after ergotamine, but not in response to saline. Plasma triiodothyronine was elevated (P < .01) 1 to 2 h after ergotamine, but not after saline. Insulin was decreased (P < .01) and glucagon increased (P < .01) within 1 h after ergotamine treatment, but they were not altered by saline. A second increase (P < .01) of glucagon occurred by 4 h after ergotamine. In Exp. 1 and 2, glucagon increased (P < .01) 1 h after oxytocin in saline and ergotamine cows. Results indicate that ergotamine can alter plasma concentrations of hormones that mediate nutrient metabolism and thermoregulation in cattle.

INCREASED PROINFLAMMATORY CYTOKINES PRODUCTION BY ERGOTAMINE IN MALE BALB/c MICE

The ergopeptine alkaloid ergotamine (ET) mimics the effects of ergopeptine alkaloids found in endophyte-infected (E+) fescue forage considered causative for fescue toxicosis. Altered immune capacity, compromised intake and thermoregulation, and inflammatory changes are observed in fescue toxicosis. Taken together, these suggest the cytokine pattern may be altered by ergot alkaloids. Thus, the objective of this study was to determine whether major splenocyte-derived cytokines-interleukin 2 (IL-2), interleukin 4 (IL-4), interferon gamma (IFN-gamma)-and macrophage-derived cytokines-interleukin 1, (IL-1), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-alpha)-were affected by ergotamine. Two sets of male BALB/c mice (n = 5/treatment) were treated with ergotamine tartrate (sc) for 10 d at doses of 0 (control), 0.4, 2, 10, or 50 mg/kg body weight. Twentyfour hours after the last treatment, splenocytes (S) were isolated from one set of animals and macrophages (MO) from the other set for determination of IL-2, IL-4, INF-gamma, and IL 1beta, IL-6, TNF-alpha, respectively. Following activation with 5 mug/ml concanavalin A (Con A) (S) and 10 mug/ml lipopolysaccharide (LPS) (MO), cells were incubated for 48 and 24 h, respectively, and supernatants were collected and assayed for respective cytokines by enzyme-linked immunosorbent assay (ELISA). Additionally, differential white blood cell (WBC) counts were performed and the neutrophil (N) :lymphocyte (L) ratio calculated. Ergotamine treatment significantly increased IL-6 levels at the 2.0 mg/kg dose and greater and TNF-alpha at the highest dose. There was no treatment effect on IL-1 , IL-2, IL-4, and IFN-gamma. Also, no effect was observed upon total and differential WBC counts as well as N:L ratio. Ergotamine affected the proinflammatory cytokine IL-6, and this increase may contribute to fescue tosicosis.

The impact of ergotamine-induced headache and ergotamine withdrawal on information processing.

Ergotamine abuse and subsequent ergotamine-induced headache is a common problem in the pharmacological treatment of migraine and other headache types; often, withdrawal therapy is necessary. This study investigated whether ergotamine abuse affects information processing and whether withdrawal therapy can lead to an improvement of information processing. We designed a standardized neurophysiological retrospective (ergotamine abuse) and prospective (ergotamine withdrawal) study in a supraregional headache outpatient clinic. Seventy-one patients abusing ergotamine derivatives with subsequent daily headache were enrolled and compared to 36 migraine patients without ergotamine intake and 36 healthy subjects. Information processing was evaluated by latencies and amplitudes of visually evoked event-related potentials (ERP) before and after ergotamine withdrawal therapy. P3 latency of the ERP was significantly increased in ergotamine abuse (442 +/- 45 ms) versus migraine (415 +/- 40 ms) and healthy subjects (410 +/- 33 ms), there was no difference between ergotamine tartrate and dihydroergotamine abuse. The migraine specific loss of habituation in information processing as measured by P3 latency could not be observed in migraine patients with ergotamine abuse. After successful withdrawal therapy in 36 patients, the abnormally prolonged P3 latency was significantly shortened (452 +/- 47 ms versus 433 +/- 30 ms; P < 0.004). Our findings imply that information processing is impaired by ergotamine abuse and can be improved but not normalized after withdrawal therapy. Furthermore, our data provide strong evidence that ergotamine, besides its peripheral effects, has a central mode of action.

Mortality of Horn Fly Larvae (Diptera: Muscidae) in Bovine Dung Supplemented with Ergotamine andN-Formyl Loline

Dung-dwelling larvae of ectoparasites of livestock such as the horn fly, Hematobia irritans (L.), may be exposed to > or = 1 different alkaloid species in dung from animals ingesting herbage of the tall fescue (Festuca arundinacea Schreb.)--endophyte association (Neotyphodium coenophialum (Morgan-Jones & W. Gams) Glenn, Bacon & Hanlin comb. nov.). First-instar horn flies were exposed to bovine dung supplemented with up to 50 microM each of N-formyl loline and ergotamine tartrate in factorial combination. In the absence of ergotamine tartrate, N-formyl loline caused a linear decline in the number of pupae recovered, and probit analysis indicated an LC50 of 36 microM. In the absence of N-formyl loline, significant quadratic responses of larvae to ergotamine tartrate were established, and probit analysis indicated a LC50 of 34 microM. An interaction (P < 0.001) was found between the 2 alkaloids for larval survival. This interaction showed that ergotamine tartrate moderated the toxicity of N-formyl loline and indicates that a membrane-bound receptor may be involved. There was no evidence of carryover of effects of alkaloids on subsequent stages of development or expressed as abnormalities of pupae or adults. Interactions between alkaloids probably are involved in other plant-herbivore relationships of endophyte-infected grasses.