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Mario Varasi - One of the best experts on this subject based on the ideXlab platform.
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Ergoline derivatives: receptor affinity and selectivity.
Farmaco (Societa chimica italiana : 1989), 1999Co-Authors: Sergio Mantegani, Enzo Brambilla, Mario VarasiAbstract:Ergot comprises a group of indole alkaloids which are predominantly found in various species of the ascomycete Claviceps. In pharmacopoeias, the sclerotia of Claviceps purpurea (Fr.) Tulasne parasitizing on rye, Secale cereale L., are designed as ergot or Secale cornutum. Now, the term ergot is used in a broader sense to describe the sclerotia of various Claviceps species growing on different host plants or their saprophytic mycelia. Due to their many fascinating features, there is a continuing and extensive interest in these secondary metabolites. Thus, the chemistry of ergot alkaloids and derivatives has presented many challenges to organic chemists. The ergot alkaloids and derivatives have attracted great interest for their broad spectrum of pharmacological action that includes central, neurohumoral and peripheral effects. These are mainly responses mediated by noradrenaline, serotonin, or dopamine receptors. No other group of natural products exhibits such a wide spectrum of biological action. For this reason, ergot has been termed a veritable treasure house of pharmacological constituents'. Moreover, ergot alkaloids have been an important stimulus in the development of new drugs by providing structural prototypes of molecules with pronounced pharmacological activities. This concise review, moving from the experience of our group in Pharmacia & Upjohn, will briefly mention the most representative Ergoline derivatives featured in the literature. Our work in this field originated compounds with quite different pharmacological activities. In fact, by continuous modification of the same main template structure, the Ergoline skeleton, it ultimately led to the development of new dopaminergic agents and to the identification of new series of serotonergic agents.
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5 10 9 abeo Ergoline derivatives synthesis 5 ht1a receptor affinity and selectivity
ChemInform, 1998Co-Authors: Sergio Mantegani, Enzo Brambilla, Carla Caccia, Robert A Mcarthur, M. G. Fornaretto, Luca Baumer, Mario VarasiAbstract:Abstract The synthesis and the structure-affinity relationship (S.A.F.I.R.) study for the 5-HT 1A receptor sites of a novel series of 5(10→9) abeo -Ergoline derivatives are presented. Most derivatives showed moderate to high affinity and selectivity for 5-HT 1A receptor sites. The structure-affinity relationship pointed out the role of the substituent at position 8, and the outstanding importance of the reduction of the indole 2,3-double bond for achieving the highest 5-HT 1A affinity and selectivity within the compounds presented.
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Serotonergic Ergoline derivatives
Bioorganic & medicinal chemistry letters, 1998Co-Authors: Enzo Brambilla, Carla Caccia, Robert A Mcarthur, M. G. Fornaretto, Gabriele Damiani, Mario VarasiAbstract:Novel classes of 13- and 14-tertbutyl-Ergoline derivatives were prepared, and characterised in vitro for their affinity for adrenergic, dopaminergic and serotonergic binding sites. This study particularly examines the importance of the presence and the position of the tert-butyl group in conferring either significant 5-HT1A or 5-HT2 affinity and selectivity respectively.
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Synthesis and in vitro and in vivo evaluation of dopaminergic Ergoline derivatives.
Farmaco (Societa chimica italiana : 1989), 1998Co-Authors: Sergio Mantegani, Gabriella Traquandi, Enrico Di Salle, Enzo Brambilla, Carla Caccia, Maria Antonietta Cervini, Robert A Mcarthur, Mario VarasiAbstract:A series of Ergoline-amides was synthesised in the discovery of new dopaminomimetic agents. Several compounds exhibited in vivo high prolactin lowering activity (indirectly measured by the nidation test) in rats. For the most active, the potential anti-Parkinson activity was evaluated by observation of the contralateral turning behaviour in 6-OH-DA lesioned rats. The acute toxicity by oral route in mice was also studied.
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Synthesis and in vitro structure-activity relationship of 13-tert-butyl-Ergoline derivatives as 5-HT1A receptor ligands
European Journal of Medicinal Chemistry, 1997Co-Authors: Enzo Brambilla, Carla Caccia, M. G. Fornaretto, R. A. Mc Arthur, Mario VarasiAbstract:Summary A series of novel 13-tert-butyl-Ergoline derivatives was prepared and evaluated for affinity to adrenergic, dopaminergic and serotonergic receptor sites. Selectivity for 5-HT1A receptors versus α1, α2, D1, D2, and 5-HT2 appears to be influenced by the presence of the tert-butyl moiety at position 13 of the Ergoline skeleton. Some compounds within this series display nanomolar 5-HT1A affinity and hundred-fold selectivity versus the other receptors considered.
Miroslav Flieger - One of the best experts on this subject based on the ideXlab platform.
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Pharmacological properties of a wide array of Ergolines at functional alpha_1-adrenoceptor subtypes
Naunyn-Schmiedeberg's Archives of Pharmacology, 2007Co-Authors: Tilo Görnemann, Miroslav Flieger, Sven Jähnichen, Reinhard Horowski, Björn Schurad, Klaus Peter Latté, Johannes Tack, Heinz H. PertzAbstract:Ergot alkaloids act as (partial) agonists or antagonists at serotonergic, dopaminergic and α-adrenergic receptors. In contrast to their affinity at serotonergic (5-HT) and dopaminergic receptor subtypes, only limited information is available concerning their interaction with α-adrenoceptor subtypes. This especially holds true for native α-adrenoceptors. Therefore, we studied the pharmacological profile of 25 Ergolines at α_1A-, α_1B- and α_1D-adrenoceptors in vascular rings or strips of rat and guinea pig endowed with these receptors. Contractile responses were studied by measurement of isometric tension changes in rat tail artery (α_1A, α_1B), guinea pig spleen (α_1B) and rat thoracic aorta (α_1D). The anti-migraine drugs ergotamine and dihydroergotamine, the anti-parkinsonian drug lisuride and the anti-hyperprolactinemic drug terguride behaved as antagonists or low-efficacy partial agonists at all three α_1-adrenoceptor subtypes with nanomolar receptor affinity. Derivatives of these drugs showed lower affinity at α_1-adrenoceptors than the parent compounds. Each individual Ergoline derivative tested showed low discriminatory capability at the subtypes, α_1A, α_1B, α_1D. A low discriminatory power between the subtypes (α_1A, α_1B, α_1D) seems to be a class effect of the Ergolines. The nanomolar affinities of ergotamine, dihydroergotamine and lisuride for α_1-adrenoceptors may affect their effectiveness as anti-migraine and anti-parkinsonian drugs, respectively.
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claviceps citrina sp nov a parasite of the halophytic grass distichlis spicata from mexico
Fungal Biology, 1998Co-Authors: Sylvie Pažoutova, Leopold Fucikovský, S G Leyvamir, Miroslav FliegerAbstract:The occurrence of an undescribed ergot species, Claviceps citrina, on the halophytic chloridoid grass Distichlis spicata, in the Texcoco region of central Mexico, is reported. RAPD and ITS1 sequences of this fungus were compared with other Claviceps species and the morphological uniqueness of the fungus was reinforced. Its sclerotia do not contain any alkaloids of the Ergoline type. Germination of sclerotia occurred immediately after placing them on humid sand. After removal of the capitula, the remaining stipe was able to regenerate the capitulum.
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analysis of ergot alkaloids in endophyte infected tall fescue by liquid chromatography electrospray ionization mass spectrometry
Journal of Agricultural and Food Chemistry, 1997Co-Authors: Richard A Shelby, Jana Olsovska, Vladimir Havlicek, Miroslav FliegerAbstract:Previous investigators have identified a number of ergot alkaloids (EAs) in tall fescue (Festuca arundinacea Schreb.) infected by the endophytic fungus, Neotyphoidium coenophialum [(Morgan-Jones & W. Gams) Glenn, Bacon & Hanlin comb. nov.]. Their results, however, may have been confounded by the presence of the related parasitic ergot fungus (Claviceps purpurea [Fr.:Fr.] Tul.), which also produces EAs. Semipreparative HPLC was used to separate fractions giving a high fluorescence response in a sample of endophyte-infected (EI) tall fescue seeds, carefully examined to eliminate the possibility of Claviceps infection. Analytical high-performance liquid chromatography (HPLC) and LC/electrospray ionization mass spectrometry (ESI-MS) were used to identify EAs after isolation. Clearly identified in the spectra were ergine, ergovaline, ergosine, ergonine, and previously undescribed EAs, didehydroergovaline and aci-ergovaline, including their epimers. Several additional EAs may have been present, but structures c...
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hplc method for detection of ergotamine ergosine and ergine after intravenous injection of a single dose
Journal of Agricultural and Food Chemistry, 1996Co-Authors: Ali S Moubarak, Edgar L Piper, Z B Johnson, Miroslav FliegerAbstract:A simple, rapid method of liquid solid extraction coupled with a sensitive HPLC procedure with fluorescence detection to measure ergot alkaloid levels in bovine blood samples is presented. Single injections of either ergosine, ergotamine, or ergine were given to Holstein steer calves (140 kg), and serum concentrations of the ergot alkaloids were monitored over a 2-h period. Serum samples were loaded on a Bond Elut (100 mg) C18 column that had been washed with methanol and distilled water. Ergot alkaloids were then eluted with methanol and analyzed by HPLC. Recovery of ergosine, when added to serum at concentrations of 0.5−24.0 ng/mL, ranged from 95 to 98%. The data fit previous reports of three phases in elimination of drug. The method reported has excellent repeatability, a detection limit of 0.5 ng/mL, and provides an alternative to quantitate ergosine, ergotamine, and ergine in bovine blood samples at therapeutic dosages. Keywords: Ergosine; ergotamine; ergine; blood; assay; HPLC
Eckhard Leistner - One of the best experts on this subject based on the ideXlab platform.
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Ergoline alkaloids in convolvulaceous host plants originate from epibiotic clavicipitaceous fungi of the genus Periglandula
Fungal Ecology, 2012Co-Authors: Ulrike Steiner, Eckhard LeistnerAbstract:Abstract Ergoline (i.e., ergot) alkaloids are a group of physiologically active natural products occurring in the taxonomically unrelated fungal and plant taxa, Clavicipitaceae and Convolvulaceae, respectively. The disjointed occurrence of Ergoline alkaloids seems to contradict the frequent observation that identical or at least structurally related natural products occur in organisms with a common evolutionary history. This problem has now been solved by the finding that not only graminaceous but also some dicotyledonous plants belonging to the family Convolvulaceae, such as Ipomoea asarifolia and Turbina corymbosa, form close associations with Ergoline alkaloid producing fungi, Periglandula ipomoeae and Periglandula turbinae. These species belong to the newly established genus Periglandula within the Clavicipitaceae. The fungus–plant associations are likely to be mutualistic symbioses.
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Fungal Origin of Ergoline Alkaloids Present in Dicotyledonous Plants (Convolvulaceae)
Physiology and Genetics, 2009Co-Authors: Eckhard Leistner, Ulrike SteinerAbstract:Ergoline (i.e. ergot) alkaloids are a group of physiologically active natural products occurring in taxonomically unrelated fungal and plant taxa, Clavicipitaceae and Convolvulaceae. The disjointed occurrence of Ergoline alkaloids seems to contradict the paradigm of chemotaxonomy that identical or at least structurally related natural products occur in taxonomically related organisms. This question has now been solved by the observation that some dicotyledonous plants belonging to the family Convolvulaceae (e.g. Ipomoea asarifolia, I. violacea and Turbina corymbosa carry epibiotic fungi. The fungi present on different plant species are not identical albeit taxonomically closely related clavicipitaceous fungi. Thus, the presence of Ergoline alkaloids in dicotyledonous plants is not based on their capacity to synthesize Ergoline alkaloids but rather on the ability to live in a symbiotic association with Ergoline alkaloid producing fungi.
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biosynthesis and accumulation of Ergoline alkaloids in a mutualistic association between ipomoea asarifolia convolvulaceae and a clavicipitalean fungus
Plant Physiology, 2008Co-Authors: Anne Markert, Ulrike Steiner, Nicola Steffan, Kerstin Ploss, Sabine Hellwig, Christel Drewke, Shuming Li, Wilhelm Boland, Eckhard LeistnerAbstract:Ergoline alkaloids occur in taxonomically unrelated taxa, such as fungi, belonging to the phylum Ascomycetes and higher plants of the family Convolvulaceae. The disjointed occurrence can be explained by the observation that plant-associated epibiotic clavicipitalean fungi capable of synthesizing Ergoline alkaloids colonize the adaxial leaf surface of certain Convolvulaceae plant species. The fungi are seed transmitted. Their capacity to synthesize Ergoline alkaloids depends on the presence of an intact differentiated host plant (e.g. Ipomoea asarifolia or Turbina corymbosa [Convolvulaceae]). Here, we present independent proof that these fungi are equipped with genetic material responsible for Ergoline alkaloid biosynthesis. The gene (dmaW) for the determinant step in Ergoline alkaloid biosynthesis was shown to be part of a cluster involved in Ergoline alkaloid formation. The dmaW gene was overexpressed in Saccharomyces cerevisiae, the encoded DmaW protein purified to homogeneity, and characterized. Neither the gene nor the biosynthetic capacity, however, was detectable in the intact I. asarifolia or the taxonomically related T. corymbosa host plants. Both plants, however, contained the Ergoline alkaloids almost exclusively, whereas alkaloids are not detectable in the associated epibiotic fungi. This indicates that a transport system may exist translocating the alkaloids from the epibiotic fungus into the plant. The association between the fungus and the plant very likely is a symbiotum in which Ergoline alkaloids play an essential role.
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Clavicipitaceous fungi associated with Ergoline alkaloid-containing convolvulaceae.
Journal of natural products, 2007Co-Authors: Mahalia A. Ahimsa-müller, Ulrike Steiner, Anne Markert, Sabine Hellwig, Christel Drewke, Volker Knoop, Eckhard LeistnerAbstract:Ergoline alkaloids are a group of physiologically active natural products occurring in taxonomically unrelated fungal and plant taxa Clavicipitaceae (Hypocreales) and Convolvulaceae (Solanales). We show in the present paper that clavicipitaceous fungi are associated with four different Ergoline alkaloid-containing plant taxa of the family Convolvulaceae. These fungi are macroscopically visible on the adaxial surface when young leaf buds are opened or are detectable by molecular biological techniques in seeds. Detectability of the fungus correlates with the absence or presence of Ergoline alkaloids within the respective plant organ. The fungi contain the gene (dmaW) responsible for the committed step in Ergoline alkaloid biosynthesis. Sequencing of ribosomal DNA (18S rDNA and internal transcribed spacer) as well as the dmaW gene (partial) and construction of phylogenetic trees show that the fungi are clavicipitaceous, not identical but very closely related.
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Elimination of Ergoline alkaloids following treatment of Ipomoea asarifolia (Convolvulaceae) with fungicides
Planta, 2004Co-Authors: Sabine Kucht, Ulrike Steiner, Julia Groß, Yasser Hussein, Torsten Grothe, Ullrich Keller, Simla Basar, Wilfried A. König, Eckhard LeistnerAbstract:Ergoline alkaloids are constituents of Clavicipitaceous fungi living on Poaceae plants. Ergoline alkaloids as well as volatile oil are also present in Ipomoea asarifolia Roem. & Schult (Convolvulaceae). Treatment of this plant with two fungicides (Folicur, Pronto Plus) eliminates the Ergoline alkaloids but not the volatile oil. Elimination of Ergoline alkaloids occurs concomitantly with loss of fungal hyphae associated with secretory glands on the upper leaf surface of the Ipomoea plant. Our observations suggest that accumulation of Ergoline alkaloids in the Convolvulaceae may depend on the presence of a plant-associated fungus.
Paul Tudzynski - One of the best experts on this subject based on the ideXlab platform.
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Biosynthetic Pathways of Ergot Alkaloids
Toxins, 2014Co-Authors: Nina Gerhards, Lisa Neubauer, Paul TudzynskiAbstract:Ergot alkaloids are nitrogen-containing natural products belonging to indole alkaloids. The best known producers are fungi of the phylum Ascomycota, e.g., Claviceps, Epichloe, Penicillium and Aspergillus species. According to their structures, ergot alkaloids can be divided into three groups: clavines, lysergic acid amides and peptides (ergopeptines). All of them share the first biosynthetic steps, which lead to the formation of the tetracyclic Ergoline ring system (except the simplest, tricyclic compound: chanoclavine). Different modifications on the Ergoline ring by specific enzymes result in an abundance of bioactive natural products, which are used as pharmaceutical drugs or precursors thereof. From the 1950s through to recent years, most of the biosynthetic pathways have been elucidated. Gene clusters from several ergot alkaloid producers have been identified by genome mining and the functions of many of those genes have been demonstrated by knock-out experiments or biochemical investigations of the overproduced enzymes.
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Biosynthetic Pathways of Ergot Alkaloids
MDPI AG, 2014Co-Authors: Nina Gerhards, Lisa Neubauer, Paul TudzynskiAbstract:Ergot alkaloids are nitrogen-containing natural products belonging to indole alkaloids. The best known producers are fungi of the phylum Ascomycota, e.g., Claviceps, Epichloë, Penicillium and Aspergillus species. According to their structures, ergot alkaloids can be divided into three groups: clavines, lysergic acid amides and peptides (ergopeptines). All of them share the first biosynthetic steps, which lead to the formation of the tetracyclic Ergoline ring system (except the simplest, tricyclic compound: chanoclavine). Different modifications on the Ergoline ring by specific enzymes result in an abundance of bioactive natural products, which are used as pharmaceutical drugs or precursors thereof. From the 1950s through to recent years, most of the biosynthetic pathways have been elucidated. Gene clusters from several ergot alkaloid producers have been identified by genome mining and the functions of many of those genes have been demonstrated by knock-out experiments or biochemical investigations of the overproduced enzymes
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chapter 2 ergot alkaloids biology and molecular biology
The Alkaloids: Chemistry and Biology, 2006Co-Authors: Christopher L. Schardl, Daniel G Panaccione, Paul TudzynskiAbstract:Publisher Summary This chapter discusses the biology and molecular biology of ergot alkaloids (EA). The EA are among the most important natural pharmaceuticals and toxins in human history. The EA are characterized by the tetracyclic Ergoline ring system or by related tricyclic alkaloids open between N(6) and C(7) (Ergoline numbering). They are categorized as clavines, lysergic acid (1) and its simple amides, and ergopeptines. The distribution of organisms possessing EA appears disjointed, including two orders of fungi and three plant families. The EA-producing fungi are in the Eurotiales and Hypocreales, two distantly related orders within the phylum Ascomycota. The main ecological roles of EA in nature are probably to protect the fungi from consumption by vertebrate and invertebrate animals. The EA produced by plant-symbiotic fungi (such as epichloe¨ endophytes) may protect the fungus by protecting the health and productivity of the host, which may otherwise suffer excessive grazing by animals. The EA, at levels typical of plants bearing these symbionts, can negatively affect the health of large mammal's as well herbivorous insects. Some clavines have substantial anti-bacterial properties, which might protect the fungus and, in some cases, their host plants from infection.
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ergot alkaloids biology and molecular biology
The Alkaloids: Chemistry and Biology, 2006Co-Authors: Christopher L. Schardl, Daniel G Panaccione, Paul TudzynskiAbstract:Publisher Summary This chapter discusses the biology and molecular biology of ergot alkaloids (EA). The EA are among the most important natural pharmaceuticals and toxins in human history. The EA are characterized by the tetracyclic Ergoline ring system or by related tricyclic alkaloids open between N(6) and C(7) (Ergoline numbering). They are categorized as clavines, lysergic acid (1) and its simple amides, and ergopeptines. The distribution of organisms possessing EA appears disjointed, including two orders of fungi and three plant families. The EA-producing fungi are in the Eurotiales and Hypocreales, two distantly related orders within the phylum Ascomycota. The main ecological roles of EA in nature are probably to protect the fungi from consumption by vertebrate and invertebrate animals. The EA produced by plant-symbiotic fungi (such as epichloe¨ endophytes) may protect the fungus by protecting the health and productivity of the host, which may otherwise suffer excessive grazing by animals. The EA, at levels typical of plants bearing these symbionts, can negatively affect the health of large mammal's as well herbivorous insects. Some clavines have substantial anti-bacterial properties, which might protect the fungus and, in some cases, their host plants from infection.
Tom Tobin - One of the best experts on this subject based on the ideXlab platform.
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electrospray tandem quadrupole mass spectrometry in the elucidation of ergot alkaloids chromatographed by hplc screening of grass or forage samples for novel toxic compounds
Journal of Mass Spectrometry, 2005Co-Authors: A F Lehner, Morrie Craig, Neil Fannin, Lowell P Bush, Tom TobinAbstract:Ergot alkaloids are mycotoxins generated by grass and grain pathogens such asClaviceps, for example. Ergot alkaloid–poisoning syndromes, such as tall fescue toxicosis from endophyte-infected tall fescue grass, are important veterinary problems for cattle, horses, sheep, pigs and chickens, with consequent impact on food, meat and dairy industries. Damage to livestock is of the order of a billion dollars a year in the United States alone. HPLC with UV and fluorescence detection are the predominant means of ergot alkaloid determination, with focus on quantitation of the marker compound ergovaline, although ELISA methods are undergoing investigation. These techniques are excellent for rapid detection, but of poor specificity in defining new or poorly characterized ergot alkaloids and related compounds. This paper demonstrates the facility of using electrospray(+) mass spectrometry with multiple reaction monitoring (MRM) detection during chromatographic examination of ergot alkaloid standards of lysergic acid, lysergol, ergonovine, ergovaline, ergotamine, ergocornine, ergocryptine and ergocrystine by HPLC. Ergoline-8 position epimers could be separated on the gradient HPLC system for ergocornine, ergocrystine and ergonovine and appeared as shoulders for ergotamine and ergovaline; epimers generally showed different patterns of relative intensity for specific MRM transitions. There was reasonable correspondence between retention of standards on the 2-mm ESI(+)MS phenyl-hexyl-based reverse phase column and those on the 4-mm C18-based column. Since up to 10% of clinical cases involving toxin exposure display unidentified chromatographic peaks, 11 samples of feed components associated with such cases were studied with developed MRM methods to attempt elucidation of crucial components if possible. Ergotamine appeared in all, ergovaline appeared in five and ergocornine appeared in six; ergonovine, ergocryptine, ergocrystine and lysergol also appeared in several. In addition, molecular weights of compounds newly revealed by mass spectrometry suggested ergosine, ergostine and ergoptine in four samples, for which standards were not available. Dehydrated products of ergotamine, ergocrystine and ergocornine were discovered, along with dihydrogenated ergocrystine and ergocryptine in seven of the samples, and the issue was raised as to whether dehydration was strictly an instrument-derived artifact. Finally, five of the samples, along with fescue seed standard, evidenced one or more of 14 new ergot alkaloids ranging in size from 381 to 611 molecular weight and with key mass spectral characteristics of ergot alkaloids, specifically the pair of peaks m/z 223 and 208, corresponding to the Ergoline ring system and its demethylated variant, respectively. It is anticipated that findings such as these will provide impetus to future development of analytical methodology for these heretofore relatively rare ergot alkaloid species. Copyright 2005 John Wiley & Sons, Ltd.
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electrospray tandem quadrupole mass spectrometry in the elucidation of ergot alkaloids chromatographed by hplc screening of grass or forage samples for novel toxic compounds
Journal of Mass Spectrometry, 2005Co-Authors: A F Lehner, Morrie Craig, Neil Fannin, Lowell P Bush, Tom TobinAbstract:Ergot alkaloids are mycotoxins generated by grass and grain pathogens such as Claviceps, for example. Ergot alkaloid-poisoning syndromes, such as tall fescue toxicosis from endophyte-infected tall fescue grass, are important veterinary problems for cattle, horses, sheep, pigs and chickens, with consequent impact on food, meat and dairy industries. Damage to livestock is of the order of a billion dollars a year in the United States alone. HPLC with UV and fluorescence detection are the predominant means of ergot alkaloid determination, with focus on quantitation of the marker compound ergovaline, although ELISA methods are undergoing investigation. These techniques are excellent for rapid detection, but of poor specificity in defining new or poorly characterized ergot alkaloids and related compounds. This paper demonstrates the facility of using electrospray(+) mass spectrometry with multiple reaction monitoring (MRM) detection during chromatographic examination of ergot alkaloid standards of lysergic acid, lysergol, ergonovine, ergovaline, ergotamine, ergocornine, ergocryptine and ergocrystine by HPLC. Ergoline-8 position epimers could be separated on the gradient HPLC system for ergocornine, ergocrystine and ergonovine and appeared as shoulders for ergotamine and ergovaline; epimers generally showed different patterns of relative intensity for specific MRM transitions. There was reasonable correspondence between retention of standards on the 2-mm ESI(+)MS phenyl-hexyl-based reverse phase column and those on the 4-mm C18-based column. Since up to 10% of clinical cases involving toxin exposure display unidentified chromatographic peaks, 11 samples of feed components associated with such cases were studied with developed MRM methods to attempt elucidation of crucial components if possible. Ergotamine appeared in all, ergovaline appeared in five and ergocornine appeared in six; ergonovine, ergocryptine, ergocrystine and lysergol also appeared in several. In addition, molecular weights of compounds newly revealed by mass spectrometry suggested ergosine, ergostine and ergoptine in four samples, for which standards were not available. Dehydrated products of ergotamine, ergocrystine and ergocornine were discovered, along with dihydrogenated ergocrystine and ergocryptine in seven of the samples, and the issue was raised as to whether dehydration was strictly an instrument-derived artifact. Finally, five of the samples, along with fescue seed standard, evidenced one or more of 14 new ergot alkaloids ranging in size from 381 to 611 molecular weight and with key mass spectral characteristics of ergot alkaloids, specifically the pair of peaks m/z 223 and 208, corresponding to the Ergoline ring system and its demethylated variant, respectively. It is anticipated that findings such as these will provide impetus to future development of analytical methodology for these heretofore relatively rare ergot alkaloid species.