Pharmacodynamics

Romergoline shows high affinity for the dopamine D₂ receptor (K_i = 6.5 nM), α₂-adrenergic receptor (K_i = 4.0 nM), and serotonin 5-HT_1A receptor (K_i = 4.0 nM).^[5] It also possesses moderate (submicromolar) affinity for the dopamine D₁ receptor (K_i = 55 nM) and ketanserin-labeled serotonin 5-HT₂ receptor (K_i = 24 nM).^[5] Conversely, the drug shows slight or negligible affinity for the α₁-adrenergic receptor (K_i = 113 nM), muscarinic acetylcholine receptors (K_i = >10,000 nM), and sigma receptors (K_i = >10,000 nM).^[5] Romergoline is said to act as both a dopamine receptor agonist and antagonist, depending on the circumstances.^[2][3][4][6] More specifically, the drug is said to act as a D₂ receptor silent antagonist under normal dopamine-replete circumstances, but in a dopamine-depleted state, it acts as a powerful dopamine D₁ receptor full agonist.^[2][3][4][6] This transformation of the drug's activity is thought to be due to development of dopamine D₁ receptor supersensitivity with dopamine depletion.^[6]

Romergoline produces hypolocomotion in rodents and monkeys, inhibits apomorphine-induced climbing behavior in rodents, causes antiemetic effects in dogs, strongly increases prolactin levels in rodents, and antagonizes amphetamine-induced toxicity in rodents.^[4][5] With dopamine depletion however, romergoline induces hyperlocomotion and contralateral turning behavior in 6-hydroxydopamine-lesioned rodents, reverses MPTP-induced akinesia and parkinsonism in monkeys, and reverses reserpine-induced hypokinesia.^[4][7][2][3] In any case, in humans, romergoline did not show significant antiparkinsonian effects in a clinical trial.^[2][3][8]

Pharmacokinetics

A metabolite of romergoline is its 6-desmethyl derivative FCE-26506.^[9]