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At least 19 recordsLinked to original sources
PubMed2001

Biotechnology and genetics of ergot alkaloids.

Ergot alkaloids, i.e. ergoline-derived toxic metabolites, are produced by a wide range of fungi, predominantly by members of the grass-parasitizing family of the Clavicipitaceae. Naturally occurring alkaloids like the D-lysergic acid amides, produced by the "ergot fungus" Claviceps purpurea, have been used as medicinal agents for a long time. The pharmacological effects of the various ergot alkaloids and their derivatives are due to the structural similarity of the tetracyclic ring system to neurotransmitters such as noradrenaline, dopamine or serotonin. In addition to "classical" indications, e.g. migraine or blood pressure regulation, there is a wide spectrum of potential new applications of this interesting group of compounds. The biotechnology of ergot alkaloids has a long tradition, and efficient parasitic and submerse production processes have been developed; the biochemistry of the pathway and the physiology of production have been worked out in detail. The recent identification of a cluster of genes involved in ergot alkaloid biosynthesis in C. purpurea and the availability of molecular genetic techniques allow the development of strategies for rational drug design of ergoline-related drugs by enzyme engineering and by biocombinatorial approaches.

Biotechnology↗
PubMed1991

Bioconversions of ergot alkaloids.

Ergot alkaloids are very important pharmaceutical substances with wide medical use. Their bioproduction is usually followed by chemical modification. Bioconversions of ergot alkaloids on an industrial scale have become more important in recent years. The aim of this study is to collect the available data on ergot alkaloid bioconversions and to show their potential applications. The paper deals with conversions of clavines, e.g. biooxidations, glycosylations of the alkaloids, and bioconversions of lysergic acid derivatives. A part of it is aimed at bioconversions of ergot alkaloids in mammalian organisms and obtaining their metabolites by biotransformation. The use of immobilized systems and cofermentation is also discussed.

Animals↗
PubMed1976

Pharmacological basis of the treatment of orthostatic disorders with ergot alkaloids.

Ergot alkaloids increase the tone of isolated canine vein strips dose-dependently in concentrations considerably lower than noradrenaline, but the maximal responses are only about one third of those to noradrenaline. This action can be blocked by prior administration of phentolamine. It is therefore concluded that the long-lasting stimulant action of ergot alkaloids on vascular smooth muscle is mediated mainly by alpha-adrenoceptors. Using the autoperfused hind limb of the cat, it has been shown that dihydroergotamine increases dose-dependently the tone of the capacitance vessels in a manner very similar to electrical stimulation of the sympathetic nerve with increasing frequencies. However, in contrast to sympathetic nerve stimulation, dihydroergotamine elicits only a very weak increase in arteriolar resistance.

Animals↗
PubMed1978

General pharmacology of ergot alkaloids.

Ergot alkaloids possess a wide and divergent spectrum of central and peripheral pharmacodynamic actions. They interfere with different receptor sites to stimulate and/or inhibit effector structures. The concept of partial agonism on alpha-adrenoreceptors has replaced the ancient hypothesis of direct stimulation of vascular and uterine smooth muscle. The mechanisms which are considered to be relevant for the therapeutic use of dihydroergotamine, a potent drug increasing venous tone, and of bromocriptine, a specific inhibitor of prolactin secretion, are discussed in more detail.

Animals↗
PubMed1995

History of ergot alkaloids from ergotism to ergometrine.

Epidemics of ergotism occurred frequently in the Middle Ages. They were a source of inspiration for artists and were popularly known as 'St. Anthony's Fire', resulting in gangrene, neurological diseases and death. It was caused by eating rye bread contaminated with the fungus claviceps purpurea. In 1582 it was described that a delivery could be hastened by administering a few spurs of the secale cornutum. The dosage was, however, very inaccurate resulting in frequent uterine ruptures. The nickname of the preparation of 'pulvis ad partum' was changed to 'pulvis ad mortem'. Therefore, after 1828 the ergot alkaloids were no longer used during delivery but only as a measure to prevent postpartum haemorrhage. From 1875 onwards many derivatives of ergot alkaloids were found. Dudley and Moir isolated ergometrine in 1932. It proved to have a very specific uterotonic action. However, because of severe and unpredictable side effects and the instability of the drug, ergometrine is not the drug of choice for either the prevention or the treatment of postpartum haemorrhage.

Ergonovine↗
PubMed2000

Progress and prospects of ergot alkaloid research.

Ergot alkaloids, produced by the plant parasitic fungi Claviceps purpurea are important pharmaceuticals. The chemistry, biosynthesis, bioconversions, physiological controls, and biochemistry have been extensively reviewed by earlier authors. We present here the research done on the organic synthesis of the ergot alkaloids during the past two decades. Our aim is to apply this knowledge to the synthesis of novel synthons and thus obtain new molecules by directed biosynthesis. The synthesis of clavine alkaloids, lysergic acid derivatives, the use of tryptophan as the starting material, the chemistry of 1,3,4,5-tetrahydrobenzo[cd]indoles, and the structure activity relationships for ergot alkaloids have been discussed. Recent advances in the molecular biology and enzymology of the fungus are also mentioned. Application of oxygen vectors and mathematical modeling in the large scale production of the alkaloids are also discussed. Finally, the review gives an overview of the use of modern analytical methods such as capillary electrophoresis and two-dimensional fluorescence spectroscopy.

Animals↗
PubMed2002

Reproductive toxicity of ergot alkaloids in mink.

Ergot alkaloids are-synthesized by fungi of the Claviceps family that infect rye as well as other cereals and grains. Since a portion of the ranch mink diet is cereal, mink are at a risk of being exposed to ergot alkaloids. This study was performed to determine the reproductive toxicity of ergot alkaloids derived from ergot-contaminated oats in mink. Four groups of 12 female mink each were fed diets containing 0, 3, 6 or 12 ppm ergot alkaloids from 2w prior to the breeding season until the kits were approximately 33-d old (133 d). Females were mated with untreated males. Ergo talkaloids caused a transient decrease in feed consumption, but body weights were unaffected. The gestation period of the mink in the 6 ppm group was longer compared to controls. The number of mink whelping varied significantly with 9 mink whelping each in the control and 3 ppm groups compared to 4 mink in the 6 ppm group and 1 in the 12 ppm group. Ergot alkaloids had a significant effect on kit survivabilitywith no kits surviving in the 12 ppm group. Serum prolactin was significantly depressed in the 3 ergot alkaloid groups compared to the control group. This study indicated that ingestion of ergot alkaloids at 3 ppm or higher resulted in reproductive toxicity in mink.

Animals↗
PubMed1997

Neuroimmunomodulation of natural killer (NK) cells by ergot alkaloid derivatives.

Ergot alkaloids (EAs), products of Claviceps spp., are widely used in various fields of clinical medicine (neurology, psychiatry, endocrinology). In the present work we studied the neuroimmunomodulative effect of EAs on activation of NK cells and their signalling pathways. Furthermore, the killing capability of rat NK cells in vitro was examined in the presence of glycosidic derivatives of elymoclavine, agroclavine, and liposome-encapsulated EAs. The engagement of appropriate NK cell membrane receptors by EAs cause an indirect enhancement of adenylyl cyclase system through inhibition of G-protein al,2-subunit (up to 50 % of control values). All of the tested EAs enhanced the rat NK cell-mediated cytotoxic activity in vitro, particularly against target cells of astrocyte origin (C-6 glioma). The present results argue for a possible EA immunomodulatory role of cell-mediated immunity in tumour regression processes.

Animals↗
PubMed1999

Interactions in sheep between tall fescue ergot alkaloids and hepatotoxic carbon tetrachloride and Senecio pyrrolizidine alkaloids.

The interaction between ergot alkaloids in endophyte-infected (E+) tall fescue (Festuca arundinacea) seed and pyrrolizidine alkaloids (PA) in tansy ragwort (TR; Senecio jacobaea) when simultaneously fed to sheep was investigated. Because of the hepatogenic effects of prolactin (PRL), it was hypothesized that low serum PRL induced by ergot alkaloids would increase the susceptibility of sheep to hepatotoxicity induced by PA. Sheep are normally resistant to PA-induced hepatotoxicity. Twenty-four wether lambs weighing 34.1 +/- 2.3 kg were used after being randomly assigned to 1 of 6 treatments of 4 wethers each. The diets offered were a control basal diet containing endophyte-free (E-) tall fescue seed, control + carbon tetrachloride (CCL4), E+ tall fescue basal diet, E+2CCl4, E(-)+TR, or E+2TR. The diets were composed of 50% alfalfa meal, 34.5% rolled barley, 5% soybean meal, 4% cane molasses, 0.5% trace mineralized salt and 6% tall fescue (E- or E+) seed. In the 2 TR treatments 25% of the alfalfa was replaced by TR. Interaction between ergot alkaloids in E+ tall fescue and PA in TR was assessed by gamma glutamyl transferase (GGTP) activity and/or sulfobromophthalein (BSP) clearance rate, both of which measure liver function. Serum GGTP activity was measured on days 14 and 28; plasma BSP clearance was monitored on days 28 and 70 by collection of blood at 4, 8 and 16 min after i.v. BSP injection. Serum PRL assays were performed on days 14, 70 and 84. Serum GGTP activity was elevated by CCl4 drenching on days 14 and 28. On day 28 TR feeding reduced GGTP activity, but there was no difference between the 2 TR treatments. There was no difference in the mean BSP half-times (t1/2) and % BSP retentions on day 28 among any of the 6 treatments. On day 70, there was no difference in the t1/2 or % BSP retention 4 min after BSP injection among any of the treatments. At 8 min after BSP injection, however, % BSP retention was significantly higher for the control +CCl4 than for the E+2CCl4 treatment. At 16 min after BSP injection, the E+ treatment had a higher mean % BSP retention value than the E+2CCl4 treatment; there were no differences among the other treatments. Serum PRL levels were reduced by E+ or CCl4 on all 3 dates of PRL evaluation. The lack of interaction between ergot alkaloids in E+ tall fescue seed and PA in TR as assessed by GGTP activity and/or BSP clearance in sheep may imply that the target sites o the 2 alkaloids are metabolically different. The low serum PRL with E+ did not increase susceptibility of sheep to CCl4 or PA.

Alkaloids↗