Ergot alkaloids pharmacological activities

Ergot alkaloids, 517 characteristics, 519 constitution, 525 dihydro-derivatives, 532 hydrolytic products, 526 pharmacological action, 533 relative sympathicolytic activities, 535... 

Ergot alkaloids were the first adrenoblockers to be studied. Despite the fact that the majority of ergot alkaloids exhibit a-adrenoblocking activity, their pharmacology is often different. In terms of chemistry, ergotamine and ergonovine are derivatives of lysergic acid. 

The delicate structures as well as the interesting patterns of pharmacological activity of certain ergot alkaloids have received continuous attention among synthetic chemists. This is especially true of derivatives of lysergic acid, and this chapter will be devoted to the most remarkable developments in syntheses of this class of natural compounds. 

In their last review about ergot alkaloids, Stoll and Hofmann (1) have given a short survey of the classic pharmacological and clinical activities of ergot derivatives. In the meantime some new, exciting results have been achieved which will be summarized here. 

The potent and versatile pharmacological activity of natural ergot alkaloids prompted investigations on the relationship between their chemical structure and physiological action. It also caused the natural alkaloids to be modified chemically and the resulting variations of pharmacological and therapeutic action to be studied. 

All ergot alkaloids which have so far been used therapeutically are lysergic acid derivatives. Representatives of the second main group, the clavine alkaloids, have also been found to be pharmacodynamically active, but as yet, none has been found to exert effects that can be utilized in therapy. The uterotonic and sympatholytic actions are less prominent in their pharmacological spectra of activity but, for example, elymoclavine and agroclavine have a pronounced central excitatory action which is attributed to their stimulation of sympathetic centers (172). 

These very different sets of potencies indicated that two distinct adrenoceptor types are likely to be associated with each set of pharmacological effects. Set A effects could be blocked by adrenergic blockers available in 1948 (dibenamine, ergot alkaloids). These were named as a/p/ia-adrenoceptors Set B effects, where IPR was the most potent agonist, was then said to interact with era-adrenoceptors. In fact, IPR was found to be devoid of any a-agonist effects. Ahlquist s work also established that NE possessed primarily a-adrenoceptor activity, while EP acted on both types of receptors. 

Of all the alkaloids that have been isolated from ergot, only a few have been subjected to an exhaustive pharmacological study. Generally speaking, the ergot alkaloids form a series of paired isomers, the levorotatory forms of which are pharmacologically active. Stoll (2) has classified the natural alkaloids as shown in Table 1. Of these natural alkaloids, ergono-... 

The clinical utility of natural EA like 3 and 4 was a prelude to broader and more precise clinical applications of semisynthetic derivatives of 1 and ergopeptines. Mukherjee and Menge (103) provide a detailed review of ergot-alkaloid modifications and the effects on their pharmacological activities. 

Ergot alkaloids are the pharmacologically active constituents of the sclerotia of various species of the parasitic fungus Claviceps. 

Ergot alkaloids (EA) are called dirty drugs , because they exhibit many different pharmacological activities (see Chapter 15). The objective of their chemical modifications is the preparation of new derivatives with higher selectivity for some types of receptors. The fact that many new drugs were developed by semisynthetic modification of natural precursors is a proof that this approach is fruitful. 

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