Ergot Alkaloids

Ergot Alkaloids Chemische Eigenschaften,Einsatz,Produktion Methoden

• Beschreibung

  The ergot alkaloids have been recognized for more than 2,000 years, but their effects are varied and complex. Because of their structural similarities with the neurotransmitters, the ergot alkaloids exhibit affinity for α-adrenergic, dopaminergic, and serotonergic receptor systems. They also block the release of vasoactive neuropeptides, such as substance P. In general, their pharmacological effects result from their action as partial agonists and antagonists on these biogenic amine receptors. Their spectrum of effects varies with their structural features. Thus, the ergot alkaloids have been largely displaced by other more selective and effective drugs, except for methysergide, which remains the gold standard for the treatment of migraine headaches.
  The ergot alkaloids are a large group of indole alkaloids isolated from the ergot fungus, Cl avi ceps purpurea, which is a plant parasite principally infecting rye. Eating grain contaminated with ergot caused a severely debilitating and painful disease during the Middle Ages called St. Anthony's Fire (ergotism), but in small doses, ergot was known to midwives for centuries for its ability to stimulate uterine contraction. Gangrene with burning pain in the extremities was one of two common presentations of ergot poisoning, which also could produce convulsions, hallucinations, severe psychosis, and death. St. Anthony was the patron saint of those who were stricken, and the Order of St. Anthony provided care for these patients. Outbreaks of “dancing mania,” which occurred between the thirteenth and sixteenth centuries, sometimes have been attributed to ergotism, and one appealing—if unprovable—theory proposes that the women accused of witchcraft in the Salem trials of 1692 were suffering from ergot-induced psychosis and convulsions. The pharmacology of the various ergot alkaloids is complex, involving actions on the adrenergic nervous system as well as a number of others.
  Ergotamine and dihydroergotamine are structurally related to biogenic amines and, because of this structural relationship, exert a broad range of pharmacological effects mediated by the adrenergic, the dopaminergic, and particularly, the serotonergic receptor systems. These are the serotonin (5-HT) 1A, 1B, 1D, and 1F receptor agonists, and they also block the release of two important vasoactive neuropeptides currently thought to be involved in migraine, substance P and calcitonin gene-related peptide. They exhibit mixed agonist/antagonist effects at the adrenergic and dopaminergic receptors. Ergotamine is a potent vasoconstrictor but also can produce vasodilatory effects depending on the degree of resistance of the vasculature. When preexisting resistance is low, vasoconstriction occurs, resulting in increased arterial blood pressure. When there is increased resistance of the vascular bed, vasodilation may occur, whereas ergotamine binding to serotonin receptors result in vasoconstrictor effects. In migraine headache, ergotamine most likely relieves cranial vascular pressure by selective vasoconstriction of arterial cranial vessel beds, thus reducing carotid blood flow, as well as by depression of central serotonergic neurons, thus mediating pain transmission.