The role of free serum tryptophan in the biphasic effect of acute ethanol administration on the concentrations of rat brain tryptophan, 5-hydroxytryptamine and 5-hydroxyindol-3-ylacetic acid. (1/122)

1. Acute administration of ethanol exerts a biphasic effect on the concentrations of rat brain tryptophan, 5-hydroxytryptamine and 5-hydroxyindol-3-ylacetic acid. Both effects are associated with corresponding changes in the availability of circulating free tryptophan. 2. The initial increases in the above concentrations are prevented by ergotamine, are unaltered by allopurinol and are potentiated by theophylline, whereas the later decreases are prevented by both ergotamine and allopurinol. 3. It is suggested that the initial enhancement by ethanol of brain tryptophan metabolism is caused by catecholamine-mediated lipolysis followed by displacement of protein-bound serum tryptophan, whereas the activation of liver tryptophaan pyrrolase, which is produced by the same mechanism, leads to the later decreases in the brain concentrations of tryptophan and its metabolites. 4. The initial effects of ethanol can be reproduced by an equicaloric dose of sucrose, and a comparison of the two treatments alone could therefore be misleading. 5. The effects of ethanol on liver and brain tryptophan metabolism have also been examined in mice, and a comparison of the results with those previously reported suggests that the ethanol effects are strain-dependent.  (+info)

Canine external carotid vasoconstriction to methysergide, ergotamine and dihydroergotamine: role of 5-HT1B/1D receptors and alpha2-adrenoceptors. (2/122)

The antimigraine drugs methysergide, ergotamine and dihydroergotamine (DHE) produce selective vasoconstriction in the external carotid bed of vagosympathectomized dogs anaesthetized with pentobarbital and artificially respired, but the receptors involved have not yet been completely characterized. Since the above drugs display affinity for several binding sites, including alpha-adrenoceptors and several 5-HT1 and 5-HT2 receptor subtypes, this study has analysed the mechanisms involved in the above responses. Intracarotid (i.c.) infusions during 1 min of methysergide (31-310 microg min(-1)), ergotamine (0.56-5.6 microg min(-1)) or DHE (5.6-31 microg min(-1)) dose-dependently reduced external carotid blood flow (ECBF) by up to 46+/-4, 37+/-4 and 49+/-5%, respectively. Blood pressure and heart rate remained unchanged. The reductions in ECBF by methysergide were abolished and even reversed to increases in animals pre-treated with GR127935 (10 microg kg(-1), i.v.). The reductions in ECBF by ergotamine and DHE remained unchanged in animals pre-treated (i.v.) with prazosin (300 microg kg(-1)), but were partly antagonized in animals pre-treated with either GR127935 (10 or 30 microg kg(-1)) or yohimbine (1000 microg kg(-1)). Pre-treatment with a combination of GR127935 (30 microg kg(-1)) and yohimbine (1000 microg kg(-1)) abolished the responses to both ergotamine and DHE. The above doses of antagonists were shown to produce selective antagonism at their respective receptors. These results suggest that the external carotid vasoconstrictor responses to methysergide primarily involve 5-HT1B/1D receptors, whereas those to ergotamine and DHE are mediated by 5-HT1B/1D receptors as well as alpha2-adrenoceptors.  (+info)

Alkaloid binding and activation of D2 dopamine receptors in cell culture. (3/122)

Ergot and pyrrolizidine alkaloids, either extracted from endophyte-infected tall fescue, synthesized, or purchased commercially, were evaluated in cultured cells to estimate their binding to the D2 dopamine receptor and subsequent effects on cyclic AMP production in GH4ZR7 cells, transfected with a rat D2 dopamine receptor. Ergopeptide alkaloid (alpha-ergocryptine, bromocryptine, ergotamine tartrate, and ergovaline) inhibition of the binding of the D2-specific radioligand, [3H]YM-09151-2, exhibited inhibition constants (K(I)) in the nanomolar range, whereas dopamine was less potent (micromolar). The lysergic acid amides (ergine and ergonovine) were 1/100th as potent as the ergopeptide alkaloids. Ergovaline and ergotamine tartrate were equally effective in inhibiting vasoactive intestinal peptide (VIP)-stimulated cyclic AMP production, with consistent nanomolar effective concentration (EC50) values. The remaining ergopeptide alkaloids (alpha-ergocryptine and bromocryptine), lysergic acid amides (ergonovine and ergine), and dopamine were 1/100th as potent. Two representative pyrrolizidines, N-formylloline and N-acetylloline, exhibited no binding activity at the D2 dopamine receptor or effects on the cyclic AMP system within the concentration ranges of nanomolar to millimolar. Our results indicate that the commercially available ergot alkaloids ergotamine tartrate and ergonovine may be used interchangeably in the D2 dopamine receptor system to simulate the effects of extracted ergovaline and ergine and to examine responses in receptor binding and the inhibition of cyclic AMP.  (+info)

Ergocryptine and other ergot alkaloids stimulate the release of [3H]dopamine from rat striatal synaptosomes. (4/122)

Ergocryptine is an ergot alkaloid that affects dopaminergic activity principally by interacting with D2-type receptors. In this study the ability of ergocryptine and several other ergot alkaloids to release [3H]dopamine from isolated nerve endings was demonstrated using in vitro superfusion of rat striatal synaptosomes. Ergocryptine, ergocristine, and bromocryptine produced an elevation in baseline dopamine release of approximately 400% with effective concentrations (EC50) of approximately 30 microM. Ergotamine, ergonovine, ergovaline, and ergocornine were devoid of activity. The time-course of the ergocryptine-stimulated release was relatively slow compared with amphetamine, nicotine, or K+-stimulated [3H]dopamine release; the maximal increase in release required a 5-min treatment. A number of receptor antagonists were examined for their ability to block ergocryptine-stimulated release. Of the dopaminergic, adrenergic, serotonergic, GABA-ergic, and cholinergic antagonists examined, only phentolamine produced a moderate attenuation in evoked release. Omission of Ca++ from the medium did not affect ergocryptine-evoked release. Following ergocryptine treatment, the synaptosomes were fully responsive to other stimulant. The results indicate that, in addition to interacting with dopamine receptors, several ergot alkaloids may produce dopaminergic effects by increasing the release of dopamine from central nerve endings. Several mechanisms to account for the evoked neurotransmitter release are discussed.  (+info)

Ergotamine in the acute treatment of migraine: a review and European consensus. (5/122)

Ergotamine has been used in clinical practice for the acute treatment of migraine for over 50 years, but there has been little agreement on its place in clinical practice. An expert group from Europe reviewed the pre-clinical and clinical data on ergotamine as it relates to the treatment of migraine. From this review, specific suggestions for the patient groups and appropriate use of ergotamine have been agreed. In essence, ergotamine, from a medical perspective, is the drug of choice in a limited number of migraine sufferers who have infrequent or long duration headaches and are likely to comply with dosing restrictions. For most migraine sufferers requiring a specific anti-migraine treatment, a triptan is generally a better option from both an efficacy and side-effect perspective.  (+info)

Ergotism related to a single dose of ergotamine tartrate in an AIDS patient treated with ritonavir. (6/122)

We report a rare case of ergotism related to a single dose of ergotamine tartrate in a man with AIDS being treated with ritonavir. He was treated with a prostacyclin analogue and made a complete recovery.  (+info)

Physiological responses of Brahman and Hereford steers to an acute ergotamine challenge. (7/122)

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.  (+info)

Ergotamine alters plasma concentrations of glucagon, insulin, cortisol, and triiodothyronine in cows. (8/122)

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.  (+info)