Cabergoline

Mechanism action of Cabergoline

The dopamine D₂ receptor is a 7-transmembrane G-protein coupled receptor associated with G_i proteins. In lactotrophs, stimulation of dopamine D₂ causes inhibition of adenylyl cyclase, which decreases intracellular cAMP concentrations and blocks IP3-dependent release of Ca²⁺ from intracellular stores. Decreases in intracellular calcium levels may also be brought about via inhibition of calcium influx through voltage-gated calcium channels, rather than via inhibition of adenylyl cyclase. Additionally, receptor activation blocks phosphorylation of p42/p44 MAPK and decreases MAPK/ERK kinase phosphorylation. Inhibition of MAPK appears to be mediated by c-Raf and B-Raf-dependent inhibition of MAPK/ERK kinase. Dopamine-stimulated growth hormone release from the pituitary gland is mediated by a decrease in intracellular calcium influx through voltage-gated calcium channels rather than via adenylyl cyclase inhibition. Stimulation of dopamine D₂ receptors in the nigrostriatal pathway leads to improvements in coordinated muscle activity in those with movement disorders. Cabergoline is a long-acting dopamine receptor agonist with a high affinity for D2 receptors. Receptor-binding studies indicate that cabergoline has low affinity for dopamine D1, α₁,- and α₂- adrenergic, and 5-HT₁- and 5-HT₂-serotonin receptors.