Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ERGOT ALKALOIDS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMedDate not supplied

[Biosynthesis of ergot alkaloids. Some new results on an old problem (Review)].

The biosynthetic pathway leading from L-tryptophan, mevalonic acid and methionine to the tetracyclic ergoline ring system of the ergot alkaloids in Claviceps species is reviewed. This pathway entails many mechanistically intriguing features. Recent studies are also discussed which reveal the stereochemical course of the isoprenylation of tryptophan and of the N-methylation of dimethylallyltryptophan (DMAT) and which shed some light on the likely steps leading from the open-chain precursors, N-methyl-DMAT to the tricyclic intermediate, chanoclavine-1. Finally, some plans are outlined to probe the evolutionary relationship of ergot alkaloid biosynthesis in fungi to that in higher plants of the family Convolvulaceae.

Biological Evolution↗
PubMed1986

Effects of ergot alkaloids on stress-induced analgesia.

Repeated, thirty minute anticipation of unavoidable painful stimulation causes endorphin-induced analgesia in rats. This type of stress-induced analgesia (SIA) develops rapidly during the first minutes of the exposure to anticipation stress. SIA can be demonstrated during the whole period of anticipation stress. Ergot drugs (DH--ergotoxine, lisuride, trans-9,10 dihydrolisuride) administered 30 min before the onset of anticipation stress, blocked completely this form of SIA. On the other hand, no effect of ergot alkaloids in the tail-flick latency, as measured under resting conditions, was observed. Possible interactions of ergot alkaloids with opiate receptors as an important mechanism by which ergot drugs affect SIA are discussed.

Animals↗
PubMed2003

Better biosynthesis of ergot alkaloids.

Different culture media containing different effectors for production of ergot-alkaloids were prepared. The culture media were inoculated with equal mycelia of Claviceps purpurea and some were incubated for 22 days and some incubated for 45 days. The medium that contained a mixture of glucose, glycine and tryptophan showed highest yield of the alkaloids and reached the maximum period for production of agroclavine faster.

Antibiotics, Antineoplastic↗
PubMed1976

Effects of dihydrogenated ergot alkaloids on the sleep-wakefulness cycle and on brain biogenic amines in the rat.

Investigations with four dihydrogenated ergot alkaloids, dihydroergotoxine, dihydroergonine, dihydroergostine and dihydro-beta-ergosine indicate that they exert similar dose dependent effects on the sleep-wakefulness cycle of the rat. The duration of wakefulness was increased, non-rapid eye movement (NREM) and, in particular, rapid eye movement (REM) sleep were shortened. 5-Hydroxytryptophan, but not apomorphine, induced similar changes of the rat sleep-wakefulness cycle. Neurochemical studies on rat brain biogenic amines indicate that dihydroergotoxine lowers homovanillic acid (HVA) levels and reduces HVA elevations after morphine or haloperidol in the striatum. In addition, the turnover of serotonin was slowed down and 5-hydroxyindoleacetic acid (5-HIAA) content in the whole brain was reduced. 5-HIAA elevation induced by clozapine was inhibited. These results suggest that the electroencephalographic changes in the rat produced by treatment with dihydrogenated ergot alkaloids reflect an enhanced level of vigilance and could be related to changes of brain biogenic amine metabolism.

Animals↗
PubMed1981

Role of organic acid metabolism in the biosynthesis of peptide ergot alkaloids.

Regulatory mechanism of primary metabolism responsible for the biosynthesis of peptide ergot alkaloids was proposed on the basis of experimental results from the production phase of Claviceps purpurea (FR.) Tul. in parasitic and saprophytic cultures. The production-phase metabolism is characterized by uncoupling of glycolysis from the citric acid cycle and by a break in this cycle at the level of the 2-exoglutarate dehydrogenase complex. This regulation is due to the inhibition by citrate and malate, i.e. the final products continuously taken up from the external medium. The rate of the intact reaction steps of the citric acid cycle is therefore not limited by the actual acetyl-CoA or oxaloacetate pool. The regulation also leads to an excessive synthesis of acetyl-CoA, 2-oxoglutarate and oxaloacetate, which represent the key metabolites of primary metabolism, and to their utilization in the biosynthesis of peptide alkaloids.

Citrates↗
PubMed1985

The treatment of senile dementia associated with cerebrovascular insufficiency: a comparative study of buflomedil and dihydrogenated ergot alkaloids.

Seventy-six patients took part in a randomized, comparative study of the efficacy of buflomedil hydrochloride and dihydrogenated ergot alkaloids in the treatment of senile dementia associated with cerebrovascular insufficiency. Efficacy was assessed by the patients' performance in four psychometric tests. The results showed that a trend in favour of the buflomedil group in three of the tests became statistically significant in the fourth. Both drugs appeared to be safe, causing no marked adverse reactions. In conclusion, buflomedil is as effective or more effective than dihydrogenated ergot alkaloids in the treatment of senile dementia associated with cerebrovascular insufficiency and could prove a valuable addition to long-term therapy if further studies support the trend shown in this study.

Aged↗
PubMed1978

Interaction of ergot alkaloids with dopaminergic receptors in the rat striatum and nucleus accumbens.

Various ergot alkaloids and derivatives were investigated for their interaction with dopaminergic receptors at the level of the rat corpus striatum and nucleus accumbens. Dihydro(DH)-ergotoxine, DH-ergocornine, DH-ergocryptine, DH-ergocristine, 2-Br-alpha-ergocryptine, ergotamine and DH-ergotamine were shown to inhibit, at micromolar concentrations, the dopamine-stimulated adenylate cyclase activity of rat striatal and nucleus accumbens homogenates. Interestingly, the inhibitory effect of the ergot drugs was higher in the nucleus accumbens than in the striatum. Moreover, the ergot drugs were more active in displacing 3H-haloperidol than 3H-dopamine from striatal membranes. The results, which are in apparent contradiction with previously obtained behavioral, pharmacological and clinical data, are discussed in the light of the possible presence in the central nervous system of distinct dopaminergic receptors with different conformations.

Adenylyl Cyclases↗
PubMed1986

The biologically active conformation of ergot alkaloids.

Molecular mechanics and NMR studies of the D ring conformation of ergot alkaloids demonstrate that both D1 and D2 forms may exist in solution. The comparison of the geometric parameters defining the spatial relations between the aromatic moieties and the basic nitrogen of conformationally restricted dopamine analogs, and that of ergolene, shows the D1 conformation to be the bioactive one.

Dopamine↗
PubMed1994

Antibody binding of circulating ergot alkaloids in cattle grazing tall fescue.

Direct evidence linking alkaloids found in endophyte-infected tall fescue forage with the livestock disorder known as fescue toxicosis is lacking. Physiologic effects of fescue toxicosis include reduced serum prolactin concentration in cattle. A monoclonal antibody specific to the lysergic moiety of ergot alkaloids was developed in mice after creating an immunogen by linking lysergol to human serum albumin. The antibody was specific to the lysergic moiety and, therefore, it cross-reacted with ergot alkaloids, lysergic acid, and lysergol. The antibody did not cross-react with alkaloid derivatives that had bromated or hydrogenated lysergic ring moieties. Fescue toxicosis conditions were elicited in yearling Angus steers by permitting them to graze endophyte-infected tall fescue containing > 650 micrograms/kg of ergovaline for 60 days. Passive immunization of steers by infusion of the monoclonal antibody increased serum prolactin concentration by 7 ng/ml, beginning immediately after infusion. Control steers did not respond to treatment with bovine serum albumin. Active immunization of yearling Angus heifers with immunogens containing lysergol or ergonovine linked to human serum albumin resulted in an antibody response.

Animal Feed↗
PubMed1978

Effect of ergot alkaloids on growth hormone and prolactin secretion in humans.

The effects of ergot alkaloids (mainly bromocriptine) on the secretion of GH and PRL in normal subjects and in pathological conditions (i.e. acromegaly and hyperprolactinemic states) are discussed. In the normal subjects, bromocriptine releases GH whereas in about 50% of acromegalics it causes a marked and long-lasting inhibition of the hormone secretion. PRL release is reduced by the drug both in normal subjects and in hyperprolactinemic states. Physiopathological studies in the humans indicate that, according to the experimental data, bromocriptine inhibits GH release in acromegaly and PRL secretion through a dopaminergic mechanism of action playing at the pituitary level. Data are reported on the effectiveness of bromocriptine in the medical treatment of acromegaly and of hyperprolactinemic states.

Acromegaly↗
PubMed2003

Biochemical outcome of blocking the ergot alkaloid pathway of a grass endophyte.

Neotyphodium sp. Lp1, an endophytic fungus from perennial ryegrass (Lolium perenne), produces the mycotoxin ergovaline in infected grasses, whereas a mutant in which a particular peptide synthetase gene is knocked out does not. We examined the impact of this knockout on other constituents of the ergot alkaloid pathway. Two simple lysergic acid amides, ergine and a previously undescribed amide, were eliminated by the knockout. Lysergic acid accumulated in the knockout endophyte, but quantities were only 13% of the total lysergic acid derivatives accumulated in the wild type. Concentrations of several clavines were not substantially affected. However, a novel clavine accumulated to higher concentrations in perennial ryegrass containing the knockout strain. The results indicate that production of simple lysergic acid amides requires the activity or products of the ergovaline-associated peptide synthetase and that the regulation of ergot alkaloid production is modified in response to the relatively late block in the pathway.

Ascomycota↗
PubMed1987

[Inhibitory effect of ergot alkaloids on nucleosides transport in cultured bovine anterior pituitary cells].

Effect of ergot alkaloids on (3H)-nucleosides uptake by dispersed cells from fresh female bovine anterior pituitary glands was examined, because we had interested in the mechanism of pituitary tumor regression following bromocriptine treatment and considered nucleic acid synthesis as an important process in the metabolism of these cells. The anterior pituitary cells were implanted on culture tubes using D-valine minimal essential medium with serum to suppress the overgrowth of fibroblasts and then maintained in L-valine Dulbecco's modified Eagle medium. (3H)-Uridine uptake by these cells was suppressed by bromocriptine, at-ergocriptine or ergotamine at a concentration varing from 10(-6) M to 10(-5) M, but not 10(-5) M of lergotrile. Among these alkaloids, bromocriptine had most strong inhibitory effect and suppressed the uptake to below 25% of control value at the concentration of 10(-5) M. Bromocriptine also inhibited the uptake of (3H)-thymidine, (3H)-cytidine, (3H)-adenosine or (3H)-guanosine in the same manner as (3H)-uridine. But neither (3H)-uracil, the base of uridine, nor (3H)-galactose uptake by cells was affected by bromocriptine. The incorporation of (3H)-uridine or (3H)-thymidine into TCA-insoluble fraction of the cells was also inhibited by bromocriptine as that in the total cells. It was suspected that bromocriptine acted on distinct transport site of both ribonucleoside and deoxyribonucleoside, because a high concentration (3.3 X 10(-5) M) of radio-inactive thymidine did not modify (3H)-uridine uptake by these cells as well as inhibitory effect of bromocriptine on it. These effect of bromocriptine were not blocked by haloperidol, known as dopamine antagonist, at the same concentration as bromocriptine, and dopamine had no effect on (3H)-uridine uptake by the cells. In addition, by adding 5 X 10(-4) M of dibutyryl cyclic AMP into the medium, the effect of bromocriptine was also not affected. These data suggest that the effect of bromocriptine on nucleoside transport in anterior pituitary cells may be dependent on the other binding site than D-2 dopamine receptor in the anterior pituitary cell membrane.

Animals↗
PubMed1977

Effect of ergot alkaloids on sulfonylurea-stimulated insulin secretion in dogs.

The insulinogenic response to a standard i.v. dose of a sulfonylurea can be markedly augmented in normal, conscious dogs if they are given 30 min earlier a single i.v. dose of dihydroergotamine (DHE). Since the parent substance ergotamine posssed no such amplifying properties, further experiments were conducted to clarify the essential structural requirements that have to be fulfilled for an ergot alkaloid to act as an amplifier of sulfonylurea-stimulated insulin secretion. Amine alkaloids ergonovine, dihydroergonovone and dihydromethylergonovine had no amplifying potency, but the hydrogenated amino acid alkaloids dihydroergocornine, dihydroergocristine and dihydroergokryptine (Hydergine) were almost as potent amplifiers as was DHE. The data indicate that (a) DHE, Hydergine and by inference all hydrogenated amino acid alkaloids are potent amplifiers of sulfonylurea-stimulated insulin secretion; (b) saturation of the double bond at C9 and C10 of the lysergic acid moiety and the pressence of an amino acid side chain are essential structual requirements for an ergot alkaloid to function as an amplifier of the action of sulfonylureas; and (c) it appears that these compounds are acting chiefly by mechanisms other than alpha-adrenergic and serotonergic receptor blockade, perhaps as regulatory molecules inducing positive cooperative changes in integral proteins of the plasma membrane of beta cells.

Animals↗
PubMed1988

A controlled study on the effect of pentoxifylline and an ergot alkaloid derivative on regional cerebral blood flow in patients with chronic cerebrovascular disease.

Regional cerebral blood flow (rCBF) in 90 patients with CBF decreased due to vascular diseases was studied by using the xenon 133 inhalation technique and a 32-detector setup. Whereas 30 patients received their standard basic therapy only and were regarded as controls, 30 others received 3 x 2 mg/day of an ergot alkaloid (co-dergocrine mesylate), and 30 others received 3 x 400 mg pentoxifylline (slow-release formulation)/day orally. Therapy was performed for eight weeks and CBF measured before start of treatment, after a four-week treatment period, and at the end of the study. CBF did not change significantly in the control group; both the pentoxifylline and the ergot alkaloid group presented with a significant increase in the CBF. This positive effect was significantly more pronounced in the pentoxifylline group and affected more ischemic than other brain tissues. In addition, symptoms like sleep disturbances, vertigo, and tinnitus improved significantly during the pentoxifylline observation period.

Cerebrovascular Circulation↗
PubMed1969

Role of glycols and tweens in the production of ergot alkaloids by Claviceps paspali.

Several glycols and Tweens markedly stimulated the production of ergot alkaloids in submerged cultures of Claviceps paspali. The role of these compounds was investigated in shake flasks and bench-scale fermentors. 2,3-Butanediol was not utilized by the fungus, and 1,2-propanediol-1-(14)C was not incorporated into the alkaloids. Glycols and Tweens lowered the surface tension of the basal medium and promoted the utilization of metabolites. In the presence of glycols and Tweens, an increased uptake of labeled sorbitol and succinic acid took place, whereas the specific radioactivity of the alkaloids was not affected. These results indicated that glycols and Tweens are not involved directly in the biosynthetic process; they apparently acted as surface-active agents, facilitating transport of metabolites into the cells.

Ascomycota↗
PubMedDate not supplied

[The chemical-toxicological analysis of ergot alkaloids].

Russian and foreign literature dealing with this topic is reviewed. Brief descriptions of methods of examinations starting from color tests and up to high-pressure liquid chromatography and mass spectrometry are presented in a chronological order. Clinical and toxicological characteristics of some ergot alkaloids are described.

Animals↗