Pharmacology · Ergot Alkaloid Pharmacology

Bromocriptine and Dopaminergic Ergots

Mechanism, indications, and adverse effects

The dopaminergic ergots are mechanistically distinct from everything in Modules 1 through 3. Where ergotamine and methylergonovine derive their clinical effects from serotonin receptor and alpha-adrenergic agonism, bromocriptine and cabergoline act primarily as dopamine D2 receptor agonists. That receptor specificity takes the drug to different targets — lactotrophs in the anterior pituitary, dopaminergic pathways in the basal ganglia, and somatotrophs in acromegaly.
The connection between receptor and indication is direct. Dopamine tonically inhibits prolactin secretion from the anterior pituitary. Hyperprolactinemia occurs when that dopaminergic inhibition is lost — from a prolactinoma, from dopamine-blocking antipsychotic drugs, or from other causes. Bromocriptine and cabergoline restore the inhibition pharmacologically. Cabergoline is preferred because its longer half-life allows twice-weekly dosing and its tolerability profile is superior.
Neuroleptic malignant syndrome is a dopamine D2 receptor blockade emergency. The antipsychotic drug responsible is stopped immediately, then bromocriptine is used to restore dopaminergic tone at the receptors that are blocked. Dantrolene is added to address the peripheral muscle rigidity and hyperthermia through a separate mechanism — sarcoplasmic reticulum calcium release blockade. Both are needed because the syndrome has central and peripheral components.
The cardiac valvulopathy card closes the adverse effects section with the most important safety distinction in this drug class. The fibrosis of valve leaflets is caused by serotonin 5-HT2B receptor agonism — the same receptor implicated in fenfluramine valvulopathy. It is a consequence of the ergot backbone that bromocriptine and cabergoline carry, not of their dopaminergic activity. Non-ergot dopamine agonists such as pramipexole and ropinirole do not cause this.
Pergolide is the historical teaching point: it was withdrawn from the US market in 2007 specifically because of valve disease documented in several studies. That withdrawal is what established the risk as a class effect of ergot dopamine agonists rather than an idiosyncratic reaction to a single compound.

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