Ergot Alkaloids

INTRODUCTION

The first mention of ergot alkaloids is dated 600 BC, referring to a dangerous excrescence found on spikes. In 400 BC some records refer as grass killer that caused abortion. It was observed that the epidemic of ergotism occurred after periods of hunger, where people presumably consume contaminated g.rain crops, containing toxic ergot sclerotia produced in wet springs and hot summers with rain.

The ergotism, caused by highly toxic alkaloids “ergot” produced by Claviceps spp, was the cause of major epidemics during the Middle Ages in Europe and the West, associated with the use of rye bread production. Among a wide variety of drugs employed in the attenuation of processes headache associated with migraine, we highlight the ergot alkaloids and their derivatives (Wolf et al., 1999).

Alkaloids “ergot” can be lysergic acid derivatives, but the main are peptides which decomposes by hydrolysis giving lysergic acid and isolysergic, amino acids and other substances. Proline is the amino acid common to all alkaloids. May be distinguished four major classes of ergot alkaloids: alkaloids clavina, lysergic acids, amides of lisergic acids and peptides of the ergot alkaloids. The most interesting class of peptides and ergot alkaloids, which are ergotamines, ergosines, ergocristines, ergocriptines, ergocormines, ergotaminines, ergosinines, ergocristinines, and ergocriptinines ergocorminines. The last five alkaloids are typified by a structure consisting of a lysergic acid, an acid dimetilpiruvico, a proline and phenylalanine, attached to amides.

Microorganisms producing ergot alkaloids are widely distributed in different taxonomic groups, especially fungi. Initially obtained in cultures of Claviceps, the ergot alkaloids, are currently extracted from Penicillium. Being the synthetic pathway common to both bodies, having as precursors tryptophan and mevalonic acid (Kozlovsky, 1999).

Studies carried out by Didekbrumec et al.(1996), about the morphological, biochemical and physiological development of the fungus Claviceps purpurea, clearly demonstrated that the synthesis of ergot alkaloids is closely linked to the life cycle of the fungus.

The ergot alkaloids and their derivatives act at the level of pharmacologically central nervous system and peripheral neurohumoral. The response is mediated by receptors of norepinephrine, serotonin, and dopamine (Mantegani et al.1999). These alkaloids are vasoconstrictors (DeGroot et al., 1998). The constant use of ergotamine has been responsible, according to Blomqvist and Palmer (1995), fatigue, plural effusion and elevated sedimentation rates. The ergometrine was previously used as a uterotonic drug action, preventing postpartum hemorrhage currently due to side effects,this medicine was abandoned (Vandongen & DeGroot, 1995).

The retention of six alkaloids (ergonovine, ergosine, ergotamine, ergocornine, ergocristine and alpha-ergocryptine) was recorded on wheat flour even after cooking (Fajardo et al.1995).

The forage grass, Festuca arundinacea, is widely distributed in grasslands in the western United States and is used in feed for sheepand horses. This grass is infected with Neotyphodium coenophialum fungus is endemic, causing the occurrence of ergot alkaloids in animal nutrition.

The intoxication caused leads to decreased enzymatic activity of alkaline phosphatase and aminotransferase. Subsequently causing low register values of serum prolactin globulins (Schultze et al., 1999). Similar effects were obtained by Paterson et al.(1995), with Acremonium coenophialum in infected pastures.

Ergot alkaloids can be detected by HPLC techniques (Flieger et al.1997). Moubarak et al.,(1996), described a method for detecting ergosine, ergotamine and ergine by HPLC technique. Ergot alkaloids were detected in 12 (12%) of the 100 cereal products analysed including organic meal bread mix, rye flour, self raising flour, wfuromeal flour, multi-seeded bread, multi-grain crackers, organic rye flakes, wheat germ, and grain pasta. In the samples in which ergot alkaloids were detected, the total levels ranged from 2 to 169 μgkg^-1 (Atanda et al., 2011).

FIRST ISOLATION

In 1943, A. Stoll and A. Hoffmann isolated the ergot alkaloids, dried sclerotia from the fungus Claviceps purpura (Fries) Tul., isolated from rye plants.

FUNGI PRODUCERS

Claviceps spp, Claviceps purpura, Claviceps paspali.

SUSCEPTIBLE FOODS

Pastures and grasses in general, rye, wheat, ryegrass, corn, oats, and other cereals, rye bread and related derivatives.

SENSITIVE ANIMALS

Cattle and grazing animals and humans.

SYMPTOMS

It affects the central nervous system (vomiting, diarrhea, ataxia, tremors and convulsions, gangrene and death) also causing constriction of arterioles or sclerotia and capillary endothelial injury, leading to necrosis gangrenous extremities. In cattle it causes symptoms consist of neurological symptoms, and hypersensitivity to noise and movement the dominant feature.

CHEMICAL CHARACTERISTICS

ERGOTAMINE

• Molecular formula: C₃₃H₃₅N₅O₅

• Molecular Weight: 581.65 g.mol^-1;

• Name: 12’Hidroxi-2’-methyl-5’α - (phenylmethyl) ergotaman-3’, 6’,18-trione;

• Physical properties: Crystal soluble dimetanoato, crystal and rhombic in dimetanoatoplate heavy and methanol in benzene elongated prism;

• Melting point: 203 ºC;

• Refractive index: [α] 25D - 125º to 155º in chloroform;

• Solubility: It is soluble only after prolonged heating at high vacuum. It’s a good hygroscopic. Darken if exposed to air. More or less soluble in 70 parts methanol, 150 parts of acetone, 300 parts of alcohol. Freely soluble in chloroform, pyridine, glacial acetyl, sparingly soluble in ethyl acetate, hardly soluble in benzene, almost insoluble in water and petroleum ether; • LD50: 62.80 mg kg-1 body weight of rats.

ERGOCRISTINE

• Molecular formula: C₃₅H₃₉N₅O₅

• Molecular Weight: 609.74 g.mol^-1;

• Name: 12’Hidroxi-2’-(1-methylethyl)-5’α - (phenylmethyl) ergotaman-3’,6’,18-trione

• Physical properties: Crystal orthorhombic;

• Melting point: 155-157 ºC;

• Refractive index: [α] 25D - 183^o of chloroform;

• Solubility: Freely soluble in ethanol and methanol,

acetone, chloroform, ethyl acetate. Slightly soluble in

ether. Practically insoluble in water and petroleum ether;

• LD₅₀: 62.80 mg kg^-1 body weight of rats.

ERGONOVINE