Ergoline derivatives: receptor affinity and selectivity

Ergot comprises a group of indole alkaloids which are predominantly found i n various species of the ascomycete Claviceps. In pharmacopoeias, the scler otia of Claviceps purpurea (Fr.) Tulasne parasitizing on rye, Secale cereal e 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 de rivatives has presented many challenges to organic chemists. The ergot alka loids and derivatives have attracted great interest for their broad spectru m of pharmacological action that includes central, neurohumoral and periphe ral effects. These are mainly responses mediated by noradrenaline, serotoni n, or dopamine receptors; No other group of natural products exhibits such a wide spectrum of biological action. For this reason, ergot has been terme d a 'veritable treasure house of pharmacological constituents'. Moreover, e rgot alkaloids have been an important stimulus in the development of new dr ugs by providing structural prototypes of molecules with pronounced pharmac ological 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 held orig inated compounds with quite different pharmacological activities. In fact, by continuous modification of the same main template structure, the ergolin e skeleton, it ultimately led to the development of new dopaminergic agents and to the identification of new series of serotonergic agents. (C) 1999 E lsevier Science S.A. All rights reserved.