LY-116467, also known as LY-062, 6-methylpergolide, or 6-methyl-8β-((methylthio)methyl)ergoline, is a dopamine receptor agonist of the ergoline family which was never marketed. It is the analogue of the antiparkinsonian agent pergolide in which the propyl group at the 6 position has been replaced with a methyl group.
The drug shows high affinity for the dopamine D2 receptor (Ki = 12nM), where it acts as a potent full agonist with similar potency and efficacy as pergolide ( = 14.5–16.2nM; = 90–97%). In addition to its dopamine receptor agonism, LY-116467 also shows high affinity for serotonin 5-HT1 and 5-HT2 receptors (K0.5 = 7.7nM and Ki = 70nM, respectively) as well as affinity for the α1- and α2-adrenergic receptors.
Compared to pergolide, LY-116467 showed 3.4-fold lower affinity for the dopamine D2 receptor, 4-fold higher affinity for the serotonin 5-HT1 receptor, and 1.3-fold lower affinity for the serotonin 5-HT2 receptor. The drug is similarly or less potent as a dopamine receptor agonist than pergolide in vivo. Whereas pergolide is a potent serotonin 5-HT2A and 5-HT2B receptor partial agonist, LY-116467 instead acted as a potent silent antagonist of these receptors. The drug is a weak antagonist of the α1- and α2-adrenergic receptors similarly to pergolide.
LY-116467 was first described in the scientific literature by 1982. It has been suggested that LY-116467 may lack the cardiac valvulopathy of pergolide and could be used clinically as a non-cardiotoxic replacement for it.
See also Substituted ergoline
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