title: Ergotamine and nicergoline - facts and myths.
abstract: Ergotamine, being a representative of naturally occurring ergoline alkaloids, derived from d-lysergic acid, and nicergoline, a d-lumilysergic acid derivative belonging to semi-synthetic ergot-derived alkaloids, display diversified affinity for adrenergic, serotoninergic, and dopamine receptors. Although introduction of triptans marginalized use of ergotamine, nicergoline is used in cerebral metabolic-vascular disorders, and dementia. Additionally, nicergoline exhibits a safety profile comparable to that of placebo, and none of the reviewed studies reported any incidence of fibrosis or ergotism with nicergoline treatment. In line with the recent data, activation of 5-HT2B receptor by ergot derivatives i.e. ergotamine, methysergide, pergolide, and carbegoline is involved in pathogenesis of drug-induced valvulopathy. In contrary structurally related drugs - lisuride and terguride do not increase the risk of valvular heart disease. It seems, that more detailed mechanistic studies on nicergoline and ergotamine might be beneficial for determining structural requirements related to activation of G-protein as well as alternative signal transduction pathways e.g. β-arrestins or different kinases, and responsible for drug liabilities.
authors.affiliation: Department of Medicinal Chemistry, Jagiellonian University Medical College, Kraków, Poland. Electronic address: pawel.zajdel@uj.edu.pl.
authors.forename: Paweł
authors.initials: P
authors.lastname: Zajdel
authors.affiliation: Department of Pharmacological Screening, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Bednarski
authors.affiliation: Department of Pharmacological Screening, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Sapa
authors.affiliation: Department of Pharmacobiology, Jagiellonian University Medical College, Kraków, Poland; Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Nowak
mesh_terms: D004878:Ergotamine / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D006349:Heart Valve Diseases / Q000139:chemically induced*; D006801:Humans; D009530:Nicergoline / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D009530:Nicergoline; D004878:Ergotamine
keywords: 5-HT(2B) agonism; Biased signaling; Ergotamine; Nicergoline; Valvunopathy