Ergoline derivatives: receptor affinity and selectivity

Abstract

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.