Romergoline
Pharmaceutical compound
From Wikipedia, the free encyclopedia
Romergoline (INN; developmental code name FCE-23884) is a dopamine receptor modulator of the ergoline family which was under development for the treatment of Parkinson's disease and psychotic disorders but was never marketed.[1][2][3][4][5][6] It is closely related to the psychedelic drug LSD in terms of chemical structure, though it is not technically a lysergamide itself as the oxygen atom of LSD's carboxamide moiety has been removed to instead form an aminomethyl moiety.[2]
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| Other names | FCE-23884; FCE23884; FCE-23,884; 4-(9,10-Didehydro-6-methylergolin-8β-yl)methylpiperazine-2,6-dione |
| Drug class | Dopamine receptor modulator |
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| Formula | C20H22N4O2 |
| Molar mass | 350.422 g·mol−1 |
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Pharmacology
Pharmacodynamics
Romergoline shows high affinity for the dopamine D2 receptor (Ki = 6.5 nM), α2-adrenergic receptor (Ki = 4.0 nM), and serotonin 5-HT1A receptor (Ki = 4.0 nM).[5] It also possesses moderate (submicromolar) affinity for the dopamine D1 receptor (Ki = 55 nM) and ketanserin-labeled serotonin 5-HT2 receptor (Ki = 24 nM).[5] Conversely, the drug shows slight or negligible affinity for the α1-adrenergic receptor (Ki = 113 nM), muscarinic acetylcholine receptors (Ki = >10,000 nM), and sigma receptors (Ki = >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]
History
Romergoline was first described in the scientific literature in 1991.[4] It was under development by Pharmacia Corporation, but its development was discontinued by the early 2000s and the drug was never marketed.[1]