Pharmacognosy

Third stage Dr. Enass Najem 2nd semester Lec:8

ERGOT, ERGOT ALKALOIDS, AND LSD

When the parasitic fungus Claviceps purpurea lives on rye and other cereal crops, a poisonous alkaloid and called ergot is produced. Ergot was the subject of great fear previously, because people who ate rye products infected with this, fungus experienced a strange and debilitating, and frequently lethal, disease. Ergot contains alkaloids that contract the blood vessels of arms and legs, preventing circulation of the blood, and gangrene results. Thus, people suffering from ergot poisoning lost their hands and legs without bleeding (ergotism), after they became darkened.

Although it was well known that ergot was very dangerous, midwives in Europe were also using it for promotion of the contraction of the womb post-parturition. Subsequently, studies of the active principle(s) of ergot responsible for the contractions were initiated.

The first alkaloid isolated in crystalline form was ergotinine , but it did not possess the uterocontracting activity. Ergotoxine was the first biologically active alkaloid isolated, and was shown to be a mixture of ergocristine, ergocornine, and related alkaloids. Ergotamine was isolated later in a pure form. The common skeleton of these ergot alkaloids is known as lysergic acid, and ergotamine comprises a structure based on lysergic acid coupled with a peptide moiety. The universal skeleton of the ergot alkaloids is known as the ergoline nucleus. It was shown by using cultivated Claviceps that the ergoline skeleton was derived biosynthetically from tryptophan and a C5 unit of mevalonic acid origin.

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Pharmacognosy

Simple lysergic acid amides, such as ergine and lysergic acid hydroxyethylamide, are obtained from the ergot that lives on wild grass. These alkaloids are also obtained from the seeds of Ipomoea violacea and Turbina corymbosa (Convolvulaceae) .

Pharmacological Acticity

Ergometrine (=ergonovine).

A potent oxytocic: it increases the basal tone, and the frequency and the strength of uterine contractions. This activity is thought to be linked to the stimulation of the α-adrenergic receptors in the myometrium.

Uterine hypotonicity is the origin of the antihemorrhagic effects of ergonovine. (In practice, methylergonovine is the preferred medication. It is more active in the uterus).

Ergotamine.

• At low doses is a potent vasoconstrictor acting by stimulation of the α- adrenergic receptors (the serotonergic receptors in case of brain blood vessels).

• The anti-migraine effect is due to constriction of the intracranial extracerebral blood vessels through the 5-HT1B receptor, and by inhibiting trigeminal neurotransmission by 5-HT1D receptors. It is also an oxytocic

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Pharmacognosy

Other Semisynthetic or Synthetic Derivatives

•Methysergide. A potent serotonergic antagonist. A basic treatment in migraine headaches.

2-Bromo-α-ergocryptine – (bromocriptine) postsynaptic dopaminergic agonist →A treatment in case of prolactin-secreting adenomas and in Parkinsonism.

LSD (=Lysergic acid diethylamide): It is a semisynthetic derivative. It is an exceptionally potent psychotomimetic (hallucinogenic ) drug. An effective oral dose is from 30 to 50 μg. It acts by interfering with normal serotonergic transmission.

Alkaloids Derived from Histidine:-

The amino acid L-histidine, containing the heterocyclic imidazole ring, is considered to be the right precursor of alkaloids that essentially comprise of this ring-system. A good number of Pilocarpus species, belonging to family Rutaceae, found to contain plethora of alkaloids with an imidazole ring, namely: pilocarpine, isopilocarpine, and pilosene. Pilocarpine constitutes 0.5-1.0% of the dried leaf material. Isopilocarpine appears to vary significantly within a range from 5 to 7.5% of the total alkaloids.

“Jaborandi” is the name of the crude drug prepared from the evergreen plants Pilocarpus jaborandi and Pilocarpus pinnatifolius, (Rutaceae family) which grow wild in South America, especially in Brazil. In South America, 13 plants in this genus are known, and all are used as the material for “Jaborandi,” which is important as the material for the extraction of pilocarpine.

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Pharmacognosy

Pilocarpine is a natural alkaloid extracted from plants of the genus Pilocarpus with cholinergic agonist activity. As a cholinergic parasympathomimetic agent, pilocarpine predominantly binds to muscarinic receptors, thereby inducing exocrine gland secretion (it promotes the secretion of sweat, saliva, and tears ) and stimulating smooth muscle in the bronchi, urinary tract, biliary tract, and intestinal tract. When applied topically to eyes, this agent stimulates the sphincter pupillae to contract, resulting in miosis; stimulates the ciliary muscle to contract, resulting in spasm of accommodation and an increase in the outflow of aqueous humor.

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