Editing Ergoline (section)

== Mechanism of action ==
The mechanism of ergoline alkaloids varies for each derivative. A variety of modifications can be made to the ergoline skeleton to produce medically relevant derivatives. Types of potential ergoline-based drugs include [[dopaminergic]], [[antidopaminergic]], [[Serotonin|serotonergic]], and [[antiserotonergic]].<ref name=":4">{{cite journal | vauthors = Mantegani S, Brambilla E, Varasi M | title = Ergoline derivatives: receptor affinity and selectivity | journal = Farmaco | volume = 54 | issue = 5 | pages = 288–296 | date = May 1999 | pmid = 10418123 | doi = 10.1016/s0014-827x(99)00028-2 }}</ref> Ergoline alkaloids often interfere with multiple receptor sites, leading to negative side effects and adding to the challenge of drug development.

=== Dopaminergic/antidopaminergic ===
Ergolines, such as ergotoxin, have been reported to inhibit the deciduoma reaction, which is reversed through injection of progesterone. Thus, it was concluded that ergotoxin, and related ergolines, act via the [[hypothalamus]] and [[pituitary gland]] to inhibit the [[secretion]] of [[prolactin]].<ref name=":4" /> Drugs such as [[bromocriptine]] interact with the dopaminergic receptor sites as agonists with selectivity for D<sub>2</sub> receptors, making them effective in treating Parkinson's disease. While the part of the ergoline alkaloid structure responsible for dopaminergic properties has yet to be identified, some reason that it is due to the pyroleethylamine moiety while others assert that it is due to the indoleethylamine partial structure.<ref name=":4" />

Antidopaminergic ergolines have found use in [[antiemetic]]s and in the treatment of [[schizophrenia]]. These substances are [[neuroleptic]] and are either an antagonist of dopamine at the postsynaptic level at the D<sub>2</sub> receptor site or an agonist of dopamine at the presynaptic level at the D<sub>1</sub> receptor site.<ref name=":4" /> The antagonist or agonist behavior of the ergolines are substrate dependent and mixed agonist/antagonist behaviors of ergoline derivatives have been reported.<ref name=":4" />

=== Serotonergic/antiserotonergic ===
The primary challenges of developing serotonergic/antiserotonergic ergolines is attributed to [[serotonin]], or 5-HT, acting on various distinct receptor sites. Similarly, ergoline alkaloids have been shown to exhibit both 5-HT agonist and antagonist behaviors for multiple receptors, such as [[metergoline]], a 5-HT<sub>1A</sub> agonist/5-HT<sub>2A</sub> antagonist, and [[mesulergine]], a 5-HT<sub>2A/2C</sub> antagonist.<ref name=":4" /> The selectivity and affinity of ergolines for certain 5-HT receptors can be improved by introducing a bulky group on the phenyl ring of the ergoline skeleton, which would prevent the interaction of ergoline derivatives with receptors.<ref name=":4" /> This methodology has been used to develop selective 5-HT<sub>1A</sub> and 5-HT<sub>2A</sub> ergolines in particular.