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PubMed1994

Ergot induced peripheral vascular insufficiency, non-interventional treatment.

We report a case of ergotamine tartrate induced severe vasospasm in the renal arteries and the arteries of the lower extremities. Classic features seen on peripheral angiography make the diagnosis. Anticoagulation, thrombolysis, vasodilation, steroids, and prostaglandin inhibitors all have been successfully used to treat symptomatic ergot induced arterial vasospasm. Although balloon angioplasty of ergot induced vasospasm has been described in case reports, ergot vasospasm is a self limited and medically treatable condition that does not require peripheral mechanical intervention, unless the immediate threat of necrosis and gangrene exists.

Adult↗

PubMed1976

Analysis of alkaloid mixtures by charge-transfer complexation.

Binary mixtures of weak and strong UV-absorbing alkaloids were analyzed by a charge-transfer spectrophotometric method, utilizing iodine in ethylene dichloride as the acceptor. In the uncomplexed form, the strong absorbing alkaloid (papaverine, quinine, ergotamine, or reserpine) was measured at a wavelength where there was no interference from weak absorbers (at 335, 332, 315, or 300 nm, respectively). The weak absorbing alkaloid (ephedrine, codeine, atropine, or homatropine methylbromide) was determined by computing its contribution to the total charge-transfer band at 295 nm where absorbance was linearly additive for mixtures. The greater increase in the original epsilon-values of the weak absorbers upon complexation with iodine relative to the corresponding increase in the epsilon-values of the strong absorbers led to good recoveries even at the low dose ratios of the weakly absorbing, and often more potent, alkaloids.

Alkaloids↗

PubMed2004

Reduction in the therapeutic intensity of abortive migraine drug use during ACE inhibition therapy--a pilot study.

INTRODUCTION: Since a few case reports have demonstrated some beneficial effects of angiotensin converting enzyme (ACE) inhibitors in migraine prevention, we were interested in studying the impact of ACE inhibitors and angiotensin II receptor antagonists (Ang II) on the consumption of specific abortive migraine drugs and, therefore, indirectly on the frequency of migraine attacks. METHODS: Data from a large prescription database involving 95 patients initiating a specific abortive migraine drug (ergotamine or a triptan) and subsequently treated with either an ACE inhibitor or angiotensin receptor antagonist (index group: ACE/Ang II) or diuretic (reference group) were analysed. The effects of ACE/Ang II inhibition as well as diuretic therapy on reducing the frequency of migraine attacks were assessed by measuring the mean consumption of abortive migraine drug use, in DDDs per month ('therapeutic intensity'), before, during and after ACE/Ang II or diuretic therapy. A 'therapeutic fluctuation intensity estimate' of abortive migraine drug use for all patients was likewise calculated. RESULTS: On an individual level, the therapeutic intensity (TI) fluctuation estimate, 'during' relative to 'before' ACE diuretic therapy, was significantly larger for the ACE/Ang II group (62% reduction) than for the diuretic group (24% reduction) (p = 0.02). For patients who continued abortive migraine drug use during and after ACE/Ang II or diuretic therapy, a significantly larger reduction in this estimate was observed during ACE/Ang II inhibition (68.9%) compared to during diuretic therapy (10.5% increase) (p = 0.004). The TI fluctuation estimate, after relative to 'during', had increased by 50.3% after ACE/Ang II inhibition and had reduced by 22.2% after diuretic treatment (p = 0.1). CONCLUSIONS: A clear reduction in the TI of abortive migraine drug use during the use of ACE inhibitors as compared to diuretic treatment was observed. Our findings may indirectly support a positive effect of ACE/Ang II inhibition on the frequency and severity of migraine attacks, as observed in other studies and reports.

Adolescent↗

PubMed1985

Potentiation of acetazolamide induced ectrodactyly in Wistar rats by vasoactive agents and physical clamping of the uterus.

The vasoactive agents serotonin, ergotamine, and nicotine potentiate acetazolamide induced forelimb ectrodactyly (missing digits) in Wistar rats. These vasoactive agents administered alone do not produce forelimb ectrodactyly and are not known to be inhibitors of carbonic anhydrase. Additionally, physical clamping of the uterine horns in addition to oral acetazolamide administration increases the frequency of forelimb ectrodactyly, suggesting that decreased uterine blood flow can potentiate acetazolamide teratogenesis. Since the vasoactive agents used in this study are reported to possess uterine vasoconstrictive activity, a decrease in uterine blood flow is a plausible mechanism for the potentiative ability of these agents.

Abnormalities, Drug-Induced↗

PubMed1996

Effects of antimigraine drugs on retinal spreading depression.

It has been suggested that spreading depression may play a role in triggering classical migraine. In this study the retinal spreading depression was used as a pharmacological tool to test the neuronal effects of several common antimigraine drugs. As the chicken retina is void of any blood vessels the observed effects must be of pure neuronal origin. It is shown that propranolol, sumatriptan, methysergide, paracetamol and acetylsalicyclic acid decrease the propagation velocity of retinal spreading depression waves, accelerate the recovery of the optical and electrical signal and reduce the amplitude of the negative potential shift, concomitant with the spreading depression. Barbiturate increases the spreading velocity, and the amplitude of the potential shift. Ergotamine, clonidine, lisuride and iprazochrome have no significant influence on retinal spreading depression.

Acetaminophen↗

PubMed1989

Long-term maintenance of improvements achieved with (abortive) pharmacological and nonpharmacological treatments for migraine: preliminary findings.

This report presents the first prospective comparison of the long-term maintenance of reductions in recurrent migraine headaches achieved with (abortive) pharmacological and nonpharmacological (combined relaxation training and thermal biofeedback training) treatments. Nineteen of 21 (90%) successfully treated patients (50% or greater reduction in headache activity) were contacted for follow-up evaluation 3 years later. Migraine sufferers who had been treated with ergotamine were less likely to still be relying on the treatment they had received and more likely to have additional medical treatment for their headaches and to be using prophylactic or narcotic medication than were migraine sufferers who had been treated with relaxation/biofeedback training. However, daily headache recordings revealed that patients in both treatment groups continued to show lower headache activity at 3-year follow-up than prior to treatment. Although preliminary, these findings raise the possibility that improvements achieved with nonpharmacological treatment are more likely to be maintained without additional treatment than are similar improvements achieved with abortive pharmacological treatment.

Adult↗

PubMed1982

Ergot alkaloids and phosphodiesterase; 'in vitro' activities in several rat brain areas.

The 'in vitro' activity of ergotamine, dihydroergocristine, dihydroergocornine and dihydroergocryptine on the phosphodiesterase system at low and high Km in several rat brain areas was examined. These drugs were found to exert an inhibitory effect in all the areas examined with regard to both systems, and particularly on low substrate concentration phosphodiesterases.

Animals↗

PubMed2000

[Surgical treatment of high anorectal and rectovaginal fistulas with the use of transanal endorectal advancement flaps].

INTRODUCTION: Sphincterotomy can be avoided in the repair of high anorectal or rectovaginal fistulas by use of rectal advancement flaps. METHODS: Between 1986 and 1998, 22 patients with high anorectal and 15 patients with rectovaginal fistulas underwent fistulectomy without sphincterotomy and consecutive transanal rectal advancement flap repair. RESULTS: Primary healing was achieved in 81% (30/37 patients). There was no disturbance of continence though anal resting pressures decreased postoperatively. Recurrences occurred in 4 of 12 patients with Crohn's disease (2 anorectal, 2 rectovaginal) and in 1 patient with traumatic anorectal fistula. There were no recurrences in patients with cryptoglandular disease, while the operation failed in 2 patients with ergotamine-induced fistulas. CONCLUSIONS: This operative approach achieves a high primary healing rate with optimal functional outcome. Despite good results the indication should be set carefully in patients with Crohn's disease.

Adult↗

PubMed2005

Patients' preference for triptans and other medications as a tool for assessing the efficacy of acute treatments for migraine.

Oral triptans are effective and well tolerated acute treatments for migraine, but clinical differences between them are small and difficult to measure in conventional clinical trials. Patient preference assesses a global measure of efficacy and tolerability, and may be a more sensitive means of distinguishing between these drugs. In a series of studies, patients consistently expressed a clear preference for triptans over their usual non-triptan acute medications, e.g., analgesics and ergotamine. Direct comparator studies of patient preference with oral triptans showed that patients could distinguish between different triptans, and between different formulations of the same triptan. Patients could even distinguish between the three oral doses of sumatriptan. The most frequently provided reasons for preference were speed of response and overall effectiveness. Patient preference is a sensitive clinical trial endpoint and physicians should consider using it when reviewing the efficacy of acute migraine medications.

Administration, Oral↗

PubMedDate not supplied

Permanent bile duct cannulation in the monkey. A model for studying intestinal absorption.

Our aim has been to obtain an experimental model where the test animal is subjected to the least amount of stress and restraint, and can serve for the repeated sampling of biliary excretion over a prolonged period of time. By using a special end-piece at the outer terminals of the two cannulas the monkeys could be given full freedom after experimentation. During the course of the study it was found that insertion of the cannula into the common bile duct led to the development of collateral pathways for passage of bile around the point of insertion. This adaption reaction for the restoration of a normal bile channel would seem to be characteristic of Rhesus monkeys, for we did not encounter it in similar experiments on dogs and minipigs. The experimental model described is intended to serve for the determination of intestinal absorption of compounds that are mainly excreted via the bile. Results with radioactive ergotamine are presented.

Animals↗

PubMed1977

Chromosomal damage induced by some ergot derivatives in vitro.

Three ergot derivatives, dihydroergotoxine, ergotamine and methysergide, were tested for their ability to induce chromosomal damage in human lymphocytes in culture. The aberration frequency was significantly increased after treatment of the cells with 0.1 microng/ml, 0.25 microng/ml and 0.5 microng/ml of each drug. However the degree of damage was considerably less than that produced by 0.1 mg/ml to 0.5 mg/ml of caffeine, which was used as a positive control and is a known mutagen in this test-system.

Caffeine↗

PubMed1977

Effects of some ergot derivatives in bone marrow of mice.

The in vivo chromosomal damaging properties of some ergot derivatives were investigated following their administration to male mice. Dihydroergotoxine, ergotamine and methysergide were injected in doses of 25, 50 and 100 mg/kg. Significant numbers of aberrations were observed in bone marrow preparations after treatment with the higher doses. Almost all the damage was in the form of chromatid aberrations. No exchange figures were observed, neither were other anamalies, such as nondisjunction or anti-mitotic activity. This frequency of damage was about 7- to 10-fold less than that produced by the powerful alkylating agent, cyclophosphamide. Thus the ergot derivatives were concluded to have weak chromosomal damaging effects in vivo only in very high doses.

Animals↗

PubMed1983

Angiotensin II: a releaser of PGI2 from fetal and newborn rabbit lungs.

Angiotensin II (AII) induces generation of prostacyclin (PGI2) in rabbit lung in vitro at different ages, i.e., fetus, newborn and adult. Particularly, neonatal rabbit lungs display a pattern of sensitivity to AII in producing PGI2, measured as 6-oxo-PGF1 alpha, which seems to be higher than that observed in fetal lungs. The PGI2 release appears to be specific for AII stimulation since the vasoconstriction induced by noradrenaline and ergotamine was not associated with generation of this lipidic material. The inability of PGI2 to relax the extralobar pulmonary artery in the newborn suggests that the lung microcirculation is the most likely site where the vasodilating and antiaggregatory functions of PGI2 may have a physiological role.

6-Ketoprostaglandin F1 alpha↗

PubMed1983

Regional differences in the response of isolated human vessels to vasoactive substances.

1. Crural, mesenteric and pulmonary vessels obtained during surgery were studied. Isometric tension was recorded and contractions were induced by potassium 127 mM (K), noradrenaline 18 microM (NA), prostaglandin F2 alpha 2.9 microM (F2 alpha), ergotamine 3.8 microM (Erg) or digoxin 1.0 microM (Dig). 2. Spontaneous myogenic activity was only observed in pulmonary veins. F2 alpha induced spontaneous activity in mesenteric arteries. 3. In all types of vessels, except in mesenteric arteries, the response to K+ had a greater amplitude than contractions developed by NA. Erg induced a slowly developing contraction in mesenteric veins but no contraction in mesenteric arteries. Dig induced a long-lasting monophasic response in arteries and a biphasic response in the veins. 4. After immersion for 30 min in a Ca-free medium the amplitudes to both NA and K+ were significantly reduced. The veins were more susceptible to the effects of Ca-deprivation than the arteries.

Digoxin↗

PubMed1991

Multiple sclerosis--is research on the wrong track?

The search for a MS virus, specific or otherwise, seems to be futile and I therefore contend that the activation mechanism of MS deserves much more attention than it has received. Could it be located in the pineal that transmits information by altering the secretion rate of melatonin, a hormone with noradrenaline or serotonin as precursor? The human pineal--and its major hormone, melatonin--is very likely to prove that it has a number of physiological roles involving the brain and perhaps other organs. There is also the possibility that a mycotoxin, ergotamine or a related alkaloid e.g. could be the triggering factor for the manifestation of MS. It is noteworthy that the geographical distribution of ergot corresponds to such an extent with the geographical distribution of MS as is shown in the present paper.

Ergotamine↗

PubMed1993

Quantitative determination of the dopamine agonist lisuride in plasma using high-performance liquid chromatography with fluorescence detection.

An HPLC method for the determination of lisuride hydrogen maleate in plasma is described. After addition of ergotamine tartrate as internal standard, plasma is extracted with diethyl ether. Following evaporation of the solvent and redissolving in methanol the extract is injected on a silica HPLC column and lisuride is monitored by fluorescence detection using an excitation wavelength of 322 nm and an emission wavelength of 405 nm. The method is sufficiently accurate and precise with a detection limit of 20 pg/ml lisuride in plasma. The usefulness of the method is demonstrated by measurements of lisuride levels after oral intake of a 0.6 mg dose of the drug by a healthy male volunteer, showing a peak level of 1266 pg/ml, 45 min after intake.

Adult↗

PubMed1990

Autonomic control of heart rate in the adult, aquatic Notophthalmus viridescens viridescens.

1. We investigated the role of the autonomic nervous system in the control of the heart rate using an isolated heart preparation. 2. Addition of the parasympathetic blocker, atropine, to the organ bath resulted in an increase in heart rate as expected. 3. Addition of the sympathetic blocker, ergotamine, to the organ bath showed no change in the heart rate. 4. Addition of the sympathetic blocker, propranolol, to the organ bath resulted in the expected decrease in heart rate. 5. Both the sympathetic and parasympathetic nervous systems appear to play a role in the control of the heart rate.

Animals↗

PubMed2005

Centrally active nonhormonal hot flash therapies.

Given the problems associated with hormonal therapy, and the prominent problem of hot flashes in menopausal women, there is a need for nonhormonal agents to alleviate hot flashes. Several compounds that appear to act on the central nervous system have been investigated. Potential mechanisms for their effects on hot flashes have been described. Bellergal (no longer available on the US market, where it was known as Bellergal-S), a combination preparation sedative that consists of low-dose phenobarbital, ergotamine tartrate, and levorotatory alkaloids of belladonna, is an old agent that was popular approximately 20 years ago; however, there is limited suggestion of efficacy for this agent. Clonidine, an older antihypertensive drug, is another centrally active agent that has been studied. Randomized trials have demonstrated that it clearly works for reducing hot flashes, but the magnitude of efficacy is somewhat limited. Toxicity from this agent limits its utility in the clinic. Methyldopa is another centrally active agent that has been studied but to a more limited degree. It appears to have minimal efficacy and too much toxicity to make it clinically useful. Anecdotal observations from a number of sources suggested that newer antidepressants can alleviate hot flashes. This led to pilot trials of venlafaxine and paroxetine, with results suggesting benefit from both drugs. Subsequently, randomized, placebo-controlled, double-blind clinical trials of venlafaxine, paroxetine, and fluoxetine were conducted. All 3 of these clinical trials demonstrated statistically significant reductions in hot flashes with these newer antidepressants compared with placebo. Pilot trials of citalopram and mirtazapine, 2 other newer antidepressants, have also suggested efficacy. Toxicity evaluations have suggested that these agents are, again, well tolerated by the majority of patients. A recent trial, however, was unable to demonstrate any benefit for fluoxetine or citalopram over a placebo. Anecdotal observations also suggested that gabapentin was helpful for alleviating hot flashes. This led to pilot trials that again suggested efficacy. Subsequently, 2 large placebo-controlled, randomized, double-blind clinical trials were conducted. Both of these demonstrated statistically significant efficacy for gabapentin compared with a placebo. This drug is relatively well tolerated by most patients. Thus, centrally active nonhormonal agents clearly do decrease hot flashes in women. The most efficacious and clinically appropriate agents for use are newer antidepressants and gabapentin. Continued evaluation of the efficacy and toxicity of these agents is ongoing.

Amines↗