ergoline and ergotoxine

The clinical pharmacokinetics of ergotamine, dihydroergotamine, ergotoxine, bromocriptine, methysergide, and lergotrile are reviewed. Generally the new radioimmunoassay methods have partially resolved the problems involved in determining some of these ergot derivatives in biologic fluids after the low doses used clinically. However, our present knowledge of their pharmacokinetics is limited and much work remains to be done in this area. Many cases show a great difference between results produced with a radioactive drug and with radioimmunoassay. The longer half-lives measured by using a radioactive derivative are apparently due to the many metabolites of ergot alkaloids. However, we still do not know the clinical importance of these metabolites. For instance, the amount of dihydroergotamine reaching the systemic circulation remains below 1% (radioimmunoassay), but according to studies performed with a radioactive derivative the absorption quotient is about 30%. Further studies are needed to resolve the problem of an apparently high "first-pas" metabolism of this and other ergot alkaloids in the liver or gastrointestinal mucosa.

Topics: Absorption; Animals; Bromocriptine; Dihydroergotamine; Ergolines; Ergot Alkaloids; Ergotamine; Half-Life; Humans; Kinetics; Methysergide

Two randomized studies to test the efficacy of a combination of Piracetam and Ergotoxin on the destabilized brainstem are reported. In the first study, a pharmacological model using Minocycline is employed. A follow-up clinical study analysed the effect of the preparation in 5 patients suffering from vertigo and other related complaints. It was seen that there was a significant improvement in the nystagmus profiles of the pharmacological model volunteers. Similarly, the patient group showed a marked improvement in symptoms, and in orientation capability as tested by Cranio-Corpo-Graphy.

Topics: Adult; Brain Stem; Double-Blind Method; Drug Therapy, Combination; Ergolines; Ergot Alkaloids; Female; Follow-Up Studies; Humans; Minocycline; Piracetam; Pyrrolidinones; Random Allocation; Tetracyclines; Vertigo

The tripeptide chains of the ergopeptines, a class of pharmacologically important D-lysergic acid alkaloid peptides, are arranged in a unique bicyclic cyclol based on an amino-terminal α-hydroxyamino acid and a terminal orthostructure. D-lysergyl-tripeptides are assembled by the nonribosomal peptide synthetases LPS1 and LPS2 of the ergot fungus Claviceps purpurea and released as N-(D-lysergyl-aminoacyl)-lactams. We show total enzymatic synthesis of ergopeptines catalyzed by a Fe²⁺/2-ketoglutarate-dependent dioxygenase (EasH) in conjunction with LPS1/LPS2. Analysis of the reaction indicated that EasH introduces a hydroxyl group into N-(D-lysergyl-aminoacyl)-lactam at α-C of the aminoacyl residue followed by spontaneous condensation with the terminal lactam carbonyl group. Sequence analysis revealed that EasH belongs to the wide and diverse family of the phytanoyl coenzyme A hydroxylases. We provide a high-resolution crystal structure of EasH that is most similar to that of phytanoyl coenzyme A hydroxylase, PhyH, from human.

Topics: Biocatalysis; Claviceps; Cyclization; Dihydroergotamine; Dioxygenases; Ergolines; Ergotamine; Humans; Hydroxylation; Lysergic Acid; Mixed Function Oxygenases; Models, Molecular; Peptide Synthases; Peptides; Protein Conformation

The degradation and epimerization of ergot alkaloids (EAs) in rye flour were investigated after baking cookies and subsequently subjecting them to an in vitro digestion model. Different steps of digestion were analyzed using salivary, gastric, and duodenal juices. The degradation and bidirectional conversion of the toxicologically relevant (R)-epimers and the biologically inactive (S)-epimers for seven pairs of EAs were determined by a HPLC method coupled with fluorescence detection. Baking cookies resulted in degradation of EAs (2-30 %) and a shift in the epimeric ratio toward the (S)-epimer for all EAs. The applied digestion model led to a selective toxification of ergotamine and ergosine, two ergotamine-type EAs. The initial percentage of the toxic (R)-epimer in relation to the total toxin content was considerably increased after digestion of cookies. Ergotamine and ergosine increased from 32 to 51 % and 35 to 55 %, respectively. In contrast, EAs of the ergotoxine type (ergocornine, α- and β-ergocryptine, and ergocristine) showed an epimeric shift toward their biologically inactive (S)-epimers. Further experiments indicated that the selective epimerization of ergotamine EAs occurs in the duodenal juice only. These results demonstrate that toxification of EAs in the intestinal tract should be taken into consideration.

Topics: Chromatography, High Pressure Liquid; Digestion; Ergolines; Ergot Alkaloids; Ergotamine; Flour; Food Contamination; Gastric Juice; Hot Temperature; Isomerism; Molecular Structure; Saliva; Secale

The isometric method of assessment of the contractility of uterine strips in vitro makes it possible to follow up systematically the response of smooth uterine musculature to oxytocin and to test the effect of selected preparations on this process. In the submitted work the author investigated the effect of methyloxytocin, magnesium sulphate, seduxene, phenergan, plegomazine and DH-ergotoxin on the uterine contractions of strips of rat and human uteri ted. Based on the results of model experiments in vitro, the author discusses the effect of the mentioned substances on the spasmogenic activity of oxytocin.

Topics: Animals; Diazepam; Ergolines; Female; Humans; In Vitro Techniques; Magnesium; Oxytocin; Promethazine; Rats; Uterine Contraction

Topics: Animals; Ergolines; Ergot Alkaloids; Liver Circulation; Liver Function Tests; Male; Rabbits; Sulfobromophthalein

The authors tested direct effect of selected ergot alkaloids (lisuride, terguride, DH-ergotoxine, DH-ergotamine and DH-ergocristine) on specific 3H-naloxone binding in the rat striatum and hippocampus. In the striatum they found that DH-ergotoxine (a substance with high affinity for noradrenergic receptors) inhibited specific 3H-naloxone binding much more strongly than lisuride and terguride (substances with a greater affinity for dopaminergic and serotoninergic receptors). DH-ergotoxine, which inhibited binding significantly more in the striatum than in the hippocampus, displayed the greatest activity. The results show differences in the degree of inhibition by the various groups of ergot alkaloids in the striatum. In the case of DH-ergotoxine there was also a difference in the degree of inhibition in the striatum and the hippocampus.

Topics: Animals; Corpus Striatum; Ergolines; Ergot Alkaloids; Hippocampus; Kinetics; Lisuride; Male; Naloxone; Rats; Receptors, Opioid; Receptors, Opioid, mu

Topics: Adult; Cerebral Angiography; Cerebral Infarction; Drug Therapy, Combination; Ergolines; Ergonovine; Ergotism; Female; Hemiplegia; Humans; Ischemic Attack, Transient; Pregnancy; Puerperal Disorders; Tomography, X-Ray Computed

The effects of a biologically active water-soluble splenic material on the rat blood pressure are described. The endovenous perfusion of the splenic material in acidified and alkalinized forms caused significant increases of the mean blood pressure in normal, vagotomized and pithed rats, showing that, in contradiction to previous reports, changes in pH did not affect its hypertensive activity. In normal rats, the hypertensive responses were not affected by the alpha- and beta-adrenoceptor antagonists: tolazoline, ergotoxine and propranolol, supporting the previously stated view that adrenergic mechanisms are not involved. In addition, the aforementioned results obtained in vagotomized and pithed rats suggest a lack of involvement of cardiac and vascular nervous mechanisms.

Topics: Animals; Blood Pressure; Ergolines; Female; Hydrogen-Ion Concentration; Male; Propranolol; Rats; Rats, Inbred Strains; Spleen; Tissue Extracts; Tolazoline; Vagotomy

Topics: Animals; Blood Pressure; Brain Ischemia; Cats; Cerebrovascular Circulation; Electroencephalography; Ergolines; Homeostasis; Hypertension; Hypotension; Nifedipine; Papaverine; Vasodilation

We have demonstrated an extensive reorganization of organelles in mammotrophs immediately following administration of ergocristine (a dopamine agonist) to estradiol-primed male rats. Our ultrastructural findings are consistent with our previous results that ergocristine can block prolactin release without any noticeable latent period. Following three-week priming of male rats with estradiol implants, ergocristine was administered by a bolus injection through an indwelling cannula. Within two min of its administration, ergocristine induced dramatic changes in the ultrastructure of mammotrophs, i.e., (1) increased numbers of secretory granules, (2) peripheral relocation of rough endoplasmic reticulum which tends to sequester secretory granules, (3) change in location of nucleus and (4) increased numbers of intracellular bodies associated with secretory granules. We suggest that the extensive ultrastructural changes that occurred in such a short period following ergocristine administration may be indications of specific factors associated with blockage of hormone release.

Topics: Animals; Catheters, Indwelling; Cytoplasmic Granules; Ergolines; Estradiol; Injections, Intra-Arterial; Male; Organoids; Pituitary Gland; Prolactin; Rats; Rats, Inbred Strains

Topics: Animals; Cholera Toxin; Cyclic AMP; Dose-Response Relationship, Drug; Ergolines; Female; Pituitary Gland; Prolactin; Rats; RNA, Messenger; Time Factors

A strain of Claviceps purpurea, designated Pepty 695/S produces ergotoxine alkaloids under particular conditions of fermentation. The onset of alkaloid synthesis occurs around the second day of cultivation. Alkaloid formation is connected with morphological and ultrastructural changes. In the first 3-5 days of cultivation short thickened, septated hyphae, organized in plectenchymatic pellets as well as large single cells are formed. The hyphae are ultrastructurally characterized by increasing number of lipid droplets, deposits of glycogen and by extended ER membranes, which apparently may form numerous vesicles. The correlations between lipid and alkaloid synthesis are discussed.

Topics: Cell Nucleus; Claviceps; Cytoplasm; Endoplasmic Reticulum; Ergolines; Glycogen; Lipids; Mitochondria; Polysaccharides; Vacuoles

Topics: Animals; Cell Nucleus; Cells, Cultured; Ergolines; Estradiol; Female; Kinetics; Pituitary Gland; Prolactin; Rats; Receptors, Estradiol; Receptors, Estrogen; RNA, Messenger; Transcription, Genetic; Triiodothyronine

Topics: Animals; Bromocriptine; Dose-Response Relationship, Drug; Ergolines; Female; Goats; Lactation; Pregnancy; Prolactin; Time Factors

Topics: Ergolines; Ergot Alkaloids; India; Plants, Medicinal

Plasma levels of prolactin (PRL), growth hormone (GH), luteinizing hormone (LH), and corticosterone (CORT) were measured in parturient Rockland-Swiss (R-S) albino mice following the daily administration for 10 days of 0.5 mg ergocornine (ERGO), 0.5 mg bromocriptine (BROMO), or sesame oil (OIL). The dams were provided with replete foster young on a daily basis so as to prevent the decline in suckling activity that normally occurs in undernourished pups of ergot-treated dams. Circulating PRL levels were significantly reduced by both ergot drugs but plasma levels of the other hormones measured were not altered. Thus, ergot drugs have relatively specific effects on PRL even in parturient animals receiving sustained high levels of suckling stimulation.

Topics: Animals; Bromocriptine; Corticosterone; Ergolines; Female; Growth Hormone; Labor, Obstetric; Lactation; Luteinizing Hormone; Mice; Pregnancy; Prolactin

Bromocriptine and its parent compound alpha-ergocryptine were investigated with respect to their ability to interact with the guanylate cyclase (E.C.4.6.1.2)-cyclic GMP system in vitro in the rat pituitary and ovary. Both bromocriptine and alpha-ergocryptine enhanced guanylate cyclase two- to threefold in both of these tissues over a concentration range of 1 nM to 1 microM. Since bromocriptine is thought to be a dopamine agonist in the pituitary, dopamine's effects on guanylate cyclase were also tested. Dopamine caused a twofold enhancement of guanylate cyclase activity in the pituitary and ovary. When bromocriptine and dopamine were used in combination, bromocriptine had to be in equal or a greater concentration with respect to dopamine in vitro to enhance guanylate cyclase activity. These findings suggest that bromocriptine's effect at the level of the pituitary and ovary may be mediated through enhancement of guanylate cyclase activity.

Topics: Animals; Bromocriptine; Dopamine; Dose-Response Relationship, Drug; Ergolines; Female; Guanylate Cyclase; Kinetics; Ovary; Pituitary Gland; Rats; Rats, Inbred Strains

Topics: Animals; Cell Nucleus; Cells, Cultured; Cyclic AMP; Ergolines; Female; Gene Expression Regulation; Genes; Pituitary Gland; Prolactin; Rats; Transcription, Genetic

Two experiments were performed to study the effects of bromocriptine and alpha-ergocryptine on oxytocin secretion in lactating rats. In both experiments, after overnight separation from their litters, rats were injected with either vehicle alone or ergot alkaloid plus vehicle; 4 h later the litters were returned. In the first experiment the mothers were conscious. Treatment did not affect suckling behaviour, number of stretch reactions or little weight gain in the first 30 min. Oxytocin injection before the second 30 min period of suckling caused no extra milk to be obtained. In the second experiment the mothers were anaesthetized with ethyl carbamate (1.1 g/kg body weight) at the time of the ergot alkaloid or vehicle injection. Changes in intramammary pressure were recorded during suckling. Ergot alkaloids altered neither the number of milk ejections caused by suckling, nor the proportion of milk ejections equivalent to 0.2 millimicron or more oxytocin. In both experiments treatment with ergot alkaloids suppressed secretion of prolactin. It is concluded that (a) in suppressing lactation, bromocriptine and alpha-ergocryptine do not inhibit oxytocin secretion as well as prolactin secretion, and that (b) prolactin secretion is not a necessary concomitant of oxytocin secretion.

Topics: Animals; Bromocriptine; Ergolines; Female; Lactation; Oxytocin; Pregnancy; Prolactin; Rats; Secretory Rate

The present work reports observations from a first study on the effect of prolactin on mucous cells of the mammalian ileum. Sprague-Dawley rats were treated with prolactin or with the prolactin-inhibitor ergocryptine. Light microscopic histochemical study revealed that ergocryptine increased the number both of Alcian Blue-positive mucous cells and of the total number of mucous cells in the ileal crypts. Prolactin treatment apparently decreased the number of Alcian Blue pH 1.0-positive (sulphated glycoprotein-containing) mucous cells on the villi but was without effect on crypt cells. The implications of these observations are discussed.

Topics: Animals; Ergolines; Glycoproteins; Histocytochemistry; Ileum; Intestinal Mucosa; Male; Prolactin; Rats

Topics: Aging; Animals; Castration; Collagen; Dihydrotestosterone; DNA; Ergolines; Estradiol; Male; Organ Size; Prostate; Rats; Seminal Vesicles; Sexual Maturation

Effects of ergocryptine (ERG) on the periparturient sow were assessed by measuring changes in prolactin, luteinizing hormone, and progesterone in plasma. Hormones in plasma were determined on samples collected daily from 21 days before parturition until postpartum day (PPD) 21. Administration of ERG completely blocked the initiation of lactation and prevented the surge in prolactin that occurred just before parturition, as compared with effects in control sows. The gestation period was shorter (P less than 0.01) in ERG-treated sows compared with the gestation period in controls. Although the number of pigs farrowed was not different between treated and control sows, the ERG-treated sows did not raise any pigs to PPD 21. Luteinizing hormone concentrations were higher (P less than 0.01) from 10 days before parturition until PPD 21, but plasma progesterone concentrations were not different in treated sows when compared with concentrations in control sows.

Topics: Animals; Ergolines; Female; Labor, Obstetric; Lactation; Luteinizing Hormone; Postpartum Period; Pregnancy; Progesterone; Prolactin; Swine

Topics: Amiloride; Chlorthalidone; Chromatography, Thin Layer; Drug Combinations; Ergolines; Metipranolol; Propanolamines; Pyrazines; Spectrophotometry

Prolactin synthesis was investigated in monolayer cultures of dispersed pituitary cells maintained in defined medium. Electrophoresis of cell extracts from cultures labeled with [35S]methionine demonstrated that treatment with the dopaminergic drug, ergocryptine, specifically inhibited prolactin synthesis. Analysis of the time course of ergocryptine effects demonstrated that prolactin synthesis decreased sharply after 1 to 2 days of treatment and appeared to reach a new level of 26 to 28% of control values after 4 to 6 days of treatment. The concentration of ergocryptine which produced half-maximal inhibition of prolactin synthesis was about 0.3 nM. The inhibition of prolactin synthesis produced by ergoctryptine treatment was reversed by removal of the ergocryptine. Dopamine, ergocryptine, and bromoergocryptine (also a dopamine agonist) all inhibited prolactin synthesis while epinephrine and norepinephrine had little effect. The concentration of prolactin mRNA in cultured cells was assayed by hybridization of total cell RNA to prolactin cDNA. Analysis of cultures treated either for varying times or with varying doses of ergocryptine demonstrated that there was a close correspondence between the inhibition of prolactin synthesis and the inhibition of prolactin mRNA levels. These studies demonstrate the ability of dopaminergic stimulation to specifically inhibit prolactin synthesis and to decrease prolactin mRNA levels in primary cultures of pituitary cells maintained in defined medium.

Topics: Animals; Bromocriptine; DNA; Dopamine; Epinephrine; Ergolines; Female; Kinetics; Norepinephrine; Nucleic Acid Hybridization; Pituitary Gland; Prolactin; Protein Biosynthesis; Rats; RNA, Messenger

Two hundred forty Sprague-Dawley rats were treated i.v. with 2.5 or 1.25 mg of N-methyl-N-nitrosourea (MNU) per 100 g body weight at 50 and 57 days of age. At 60 days of age, rats given either dose were divided into 4 groups (30 rats/group) and treated as follows: Group 1, controls; Group 2, 0.4 mg 2-bromo-alpha-ergocryptine (CB-154) per 100 g body weight injected s.c. once daily; Group 3, retinyl acetate (328 mg/kg diet) fed daily; and Group 4, CB-154 and retinyl acetate treatments combined. Rats that received the 2.5-mg dose of MNU were treated for 129 days; those that received the 1.25-mg dose of MNU were treated for 175 days. The rats that were treated with the high dose of MNU were maintained without any treatment for an additional 13 weeks, after which they were sacrificed. The rats that were treated with the low dose of the carcinogen were sacrificed immediately after treatment. All rats were palpated once weekly for palpable mammary tumors. The number of rats with mammary tumors and the total number of mammary tumors at cessation of treatments were, respectively, as follows. MNU (2.5 mg): Group 1, 22 of 30 (73%), 82: Group 2, 11 of 30 (37%), 17; Group 3, 11 of 30 (37%), 19: Group 4, 2 of 30 (7%), 2. MNU (1.25 mg): Group 1, 8 of 30 (27%), 14; Group 2, 4 of 30 (13%), 5; Group 3, 3 of 30 (10%), 4; Group 4, 0 of 30, (0%), 0. Thus, chronic CB-154 treatment or retinyl acetate feeding markedly reduced the percentage of rates bearing mammary tumors and the total number of mammary tumors. The combined treatments were superior to either treatment alone, inasmuch as mammary tumorigenesis was nearly completely blocked in the rats of Group 4 that received the 2.5-mg dose of MNU and was totally blocked in the rats of Group 4 that received the 1.25-mg dose of MNU. Retinyl acetate feeding or CB-154-induced prolactin suppression appear to be equally effective treatments in the prophylaxis of MNU-induced mammary tumorigenesis in rats; the combined modality, however, appears to be far superior than either treatment alone.

Topics: Adrenal Glands; Animals; Depression, Chemical; Drug Synergism; Ergolines; Female; Mammary Neoplasms, Experimental; Methylnitrosourea; Nitrosourea Compounds; Organ Size; Ovary; Pituitary Gland; Prolactin; Rats; Time Factors; Tretinoin

Topics: Animals; Anticoagulants; Aorta, Abdominal; Aspirin; Blood Vessel Prosthesis; Dipyridamole; Dogs; Ergolines; Female; Iliac Artery; Jugular Veins; Male; Papaverine; Premedication; Preoperative Care; Thrombosis; Transplantation, Autologous

Effects of ergocornine and reserpine on tail resorption during metamorphosis in Bufo bufo japonicus tadpoles were studied. At prometamorphosis, ergocornine induced precocious tail resorption, while reserpine scarcely affected the tail size. At the climax of metamorphosis, ergocornine was almost ineffective in accelerating tail resorption, while reserpine was effective in inhibiting tail resorption. Since prolactin-like hormone is known to block the tail resorption induced by thyroid hormones, it was postulated that the release of the hormone is blocked by ergocornine during prometamorphosis and stimulated by reserpine during climax.

Topics: Animals; Bufonidae; Ergolines; Larva; Metamorphosis, Biological; Reserpine

Topics: Biological Products; Chromatography; Chromatography, Thin Layer; Ergolines; Ergonovine; Ergot Alkaloids; Ergotamine; Research

Topics: Alkaloids; Claviceps; Ergolines; Ergonovine; Ergot Alkaloids; Ergotamine; Humans; Russia; Sympatholytics

Topics: Biological Products; Chromatography; Chromatography, Thin Layer; Ergolines; Ergonovine; Ergot Alkaloids; Ergotamine; Research

Topics: Alkaloids; Chemistry, Pharmaceutical; Countercurrent Distribution; Ergolines; Ergot Alkaloids; Ergotamine; Oxytocics; Pharmacy

Topics: Alkaloids; Diabetes Complications; Diabetic Angiopathies; Ergolines; Ergot Alkaloids; Gangrene; Humans; Thrombophlebitis; Varicose Ulcer

Topics: Decidua; Embryo Implantation; Ergolines; Female; Humans; Ovum; Uterus

Topics: Cardiovascular Agents; Chromatography; Dihydroergotoxine; Ergolines; Ergot Alkaloids; Oxytocics

Topics: Animals; Ergolines; Ergot Alkaloids; Female; Hormones; Pituitary Gland; Pituitary Gland, Anterior; Pregnancy; Prolactin; Rats

Topics: Ergolines; Ergot Alkaloids; Estrone; Humans

Topics: Animals; Ergolines; Ergot Alkaloids; Female; Gonadotropins; Gonadotropins, Pituitary; Pituitary Diseases; Pituitary Gland; Pregnancy; Rats

Topics: Cardiovascular Agents; Chromatography, Paper; Ergolines; Ergot Alkaloids; Ergotamine; Oxytocics

Topics: Animals; Ergolines; Ergot Alkaloids; Estrous Cycle; Estrus; Female; Humans; Pregnancy; Pseudopregnancy; Rats

Topics: Alkaloids; Cardiovascular Agents; Ergolines; Ergot Alkaloids; Female; Humans; Uterus

Topics: Animals; Cardiovascular Agents; Ergolines; Ergot Alkaloids; Guinea Pigs; Hydrogenation; Hyperthyroidism

Topics: Ergolines; Ergot Alkaloids; Humans; Hypertension; Outpatients

Topics: Cardiovascular Agents; Chromatography; Chromatography, Paper; Ergolines; Ergot Alkaloids

Topics: Analgesia; Anesthesia; Anesthesia and Analgesia; Ergolines; Ergot Alkaloids; Hibernation; Neurosurgery; Pain Management

Topics: Deciduoma; Ergolines; Ergot Alkaloids; Female; Humans; Progesterone; Uterine Neoplasms

Topics: Animals; Decidua; Deciduoma; Ergolines; Ergot Alkaloids; Female; Humans; Progesterone; Pseudopregnancy; Rats

Topics: Alkaloids; Cardiovascular Agents; Ergolines; Ergot Alkaloids; Humans; Hypertension

Topics: Cardiovascular Agents; Chromatography; Ergolines; Ergot Alkaloids; Ergotamine; Oxytocics

Topics: Ergolines; Ergonovine; Female; Humans; Muscle Contraction; Uterus

Topics: Cardiovascular Agents; Chromatography, Paper; Ergolines; Ergot Alkaloids; Oxytocics

Topics: Alkaloids; Blood; Ergolines; Ergot Alkaloids

Topics: Blood Pressure; Epinephrine; Ergolines; Ergot Alkaloids; Humans; Norepinephrine

Topics: Adrenergic Antagonists; Alkaloids; Ergolines; Ergonovine; Ergot Alkaloids; Humans

Topics: Ergolines; Ergonovine; Ergot Alkaloids; Hyperkinesis; Hypothermia

Topics: Ergolines; Ergot Alkaloids; Ergotamine; Isoproterenol; Norepinephrine

Topics: Animals; Claviceps; Ergolines; Ergonovine; Ergot Alkaloids; Oxygen; Oxygen Consumption; Rats; Temperature

Topics: Animals; Body Temperature; Claviceps; Ergolines; Ergot Alkaloids; Hyperkinesis; Hypothermia; Rats; Temperature

Topics: Animals; Claviceps; Ergolines; Ergonovine; Ergot Alkaloids; Injections, Intraperitoneal; Rats

Topics: Animals; Claviceps; Convulsive Therapy; Ergolines; Ergot Alkaloids; Rats