Lisuride, a Dopamine Receptor Agonist With 5-HT2B Receptor Antagonist Properties: Absence of Cardiac Valvulopathy Adverse Drug Reaction Reports Supports the Concept of a Crucial Role for 5-HT2B Receptor Agonism in Cardiac Valvular Fibrosis

  title={Lisuride, a Dopamine Receptor Agonist With 5-HT2B Receptor Antagonist Properties: Absence of Cardiac Valvulopathy Adverse Drug Reaction Reports Supports the Concept of a Crucial Role for 5-HT2B Receptor Agonism in Cardiac Valvular Fibrosis},
  author={Caroline Hofmann and U Penner and Rainer Dorow and Heinz H. Pertz and Sven J{\"a}hnichen and Reinhard Horowski and Klaus Peter Latt{\'e} and Dirk Palla and Bj{\"o}rn Schurad},
  journal={Clinical Neuropharmacology},
Objectives: The high incidence of fibrotic cardiac valvulopathies reported in association with the 8&bgr;-ergoline dopamine (DA) agonist, pergolide, and also case reports for cabergoline and bromocriptine have made it necessary to review the theoretical basis and actual findings in the case of another DA agonist, the 8&agr;-ergoline lisuride (used since the 1970s for migraine prophylaxis as well as since the 1980s for its prolactin-lowering and anti-Parkinson activity). Methods: We have… 

Characterization of the Molecular Fragment That Is Responsible for Agonism of Pergolide at Serotonin 5-Hydroxytryptamine2B and 5-Hydroxytryptamine2A Receptors

It is concluded that the N(6) propyl substituent of pergolide is crucial for 5-HT2B receptor agonism and thus a determinant of valvular regurgitation.

The Bulky N(6) Substituent of Cabergoline Is Responsible for Agonism of This Drug at 5-Hydroxytryptamine (5-HT)2A and 5-HT2B Receptors and Thus Is a Determinant of Valvular Heart Disease

It is concluded that the bulky N(6) substituent of cabergoline is responsible for 5- HT2AR and 5-HT2BR agonism and the increased ERK1/2 phosphorylation and production of extracellular matrix by Cabergoline are mediated by 5-ht2ARs.

Transdermal delivery of dopamine receptor agonists.

  • H. Reichmann
  • Biology, Medicine
    Parkinsonism & related disorders
  • 2009

Serotonergic drugs and valvular heart disease

A more likely cause of fenfluramines-induced valvulopathy is activation of 5-HT2B receptors on heart valves by the metabolite norfenfluramine, and future serotonergic medications should be designed to lack 5- HT2B agonist activity.

Dopamine Agonists in Parkinson Disease : Special Focus on Pramipexole

In addition to abating the core symptoms of PD and delaying the onset of motor complications, the dopamine agonist pramipexole has been shown to ameliorate tremor and depressive symptoms in clinical practice.

Current and prospective pharmacological targets in relation to antimigraine action

Pharmacological targets in migraine are discussed, with special emphasis on compounds acting on 5-HT (5-HT1–7), adrenergic (α1, α2, and β), cortisol, calcitonin gene-related peptide, adenosine, glutamate, NMDA, AMPA, kainate, and metabotropic receptors, dopamine, endothelin, and female hormone (estrogen and progesterone) receptors.

Risk of heart failure following treatment with dopamine agonists in Parkinson's disease patients

The pharmacodynamic and cardiovascular effects of DAs on PD patients are reviewed, and results showed higher heart failure risk following use of pramipexole or cabergoline.

Structural determinants of 5-HT2B receptor activation and biased agonism

Four crystal structures of a prototypical serotonin receptor 5-HT2BR in complex with chemically and pharmacologically diverse drugs elucidate the structural bases for receptor activation, agonist-mediated biased signaling and β-arrestin2 translocation.

Dopamine agonists and valvular heart disease

Dopamine agonist doses in prolactinoma therapy are 10-fold lower than those employed in Parkinson's disease, although occasionally dopamine agonist-resistant patients require higher doses, and the risk for valvulopathy appears low.

Cardiovascular toxicity of novel psychoactive drugs: Lessons from the past




Agonism at 5-HT2B receptors is not a class effect of the ergolines.

Evidence for Possible Involvement of 5-HT2B Receptors in the Cardiac Valvulopathy Associated With Fenfluramine and Other Serotonergic Medications

It is suggested that all clinically available medications with serotonergic activity and their active metabolites be screened for agonist activity at 5-HT2B receptors and that clinicians should consider suspending their use of medications with significant activity at5-HT1B receptors.

Severe multivalvular heart disease: A new complication of the ergot derivative dopamine agonists

  • J. HorvathR. Fross A. Lang
  • Medicine, Biology
    Movement disorders : official journal of the Movement Disorder Society
  • 2004
It is proposed that an assessment of cardiac function be performed before and in the course of a long‐term therapy with ergot derivative dopamine agonists, suggesting that the authors may well be facing a novel, yet unrecognized, complication of this class of agents.

New concerns about old drugs: Valvular heart disease on ergot derivative dopamine agonists as an exemplary situation of pharmacovigilance

The present issue of Movement Disorders contains two studies discussing clinical observations on pergolide and related ergot dopaminergic agonist-induced fibrosis and raised several crucial questions, which highlight the dilemma embodied in the discipline of pharmacovigilance.

Retrospective evaluation of cardio-pulmonary fibrotic side effects in symptomatic patients from a group of 234 Parkinson’s disease patients treated with cabergoline

A retrospective study of Parkinson’s disease patients on chronic cabergoline monotherapy or adjunctive treatment to identify symptoms suggestive of pleuro-pulmonary, cardiac or retroperitoneal fibrosis suggests a low risk of fibrotic side effects with Cabergoline, particularly cardiac valvulopathy.

3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") induces fenfluramine-like proliferative actions on human cardiac valvular interstitial cells in vitro.

It is found that long-term MDMA use could lead to the development of fenfluramine-like VHD, and the necessity of screening current and future drugs at h5-HT2B receptors for agonist actions before their use in humans is underscored.

Continuous lisuride effects on central dopaminergic mechanisms in Parkinson's disease

It is suggested that alterations at both presynaptic and postsynaptic levels contributing to these motor complications tend to normalize with the more physiological stimulation afforded by continuous replacement strategies, especially when given chronically.

Fibrosis associated with dopamine agonist therapy in Parkinson's disease.

The results indicate, to a certain extent, that the relative risk for onset of dopamine agonist-related fibrotic syndromes is lower particularly for pramipexole and lisuride, which have been available for more years than pramipesxole.

Activation of Meningeal 5‐HT2B Receptors: An Early Step in the Generation of Migraine Headache?

The hypothesis that 5‐HT2B receptors located on endothelial cells of meningeal blood vessels trigger migraine headache through the formation of nitric oxide is supported.