Pharmacodynamics<unk>  is a ligand of dopamine, serotonin, and adrenergic receptors as well as the histamine H1 receptor. It has sub-nanomolar affinity for the dopamine D2, and D3 receptors, serotonin 5-HT1A and 5-HT1D receptors, and α2A-, α2B-, and α2C-adrenergic receptors, and low-nanomolar affinity for the dopamine D1, D4, and D5 receptors, serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors, α1A-, α1B-, and α1D-adrenergic receptors, and histamine H1 receptor.<unk>  is a partial agonist of the D2, D3, D4, 5-HT2A, 5-HT2C, and H1 receptors, a full or near-full agonist of the 5-HT1A, 5-HT1B, and 5-HT1D receptors, and a silent antagonist of the 5-HT2B receptor and α1A-, α2A-, α2B-, and α2C-adrenergic receptors. Due to its highly non-selective pharmacological activity,<unk>  is described as a "dirty drug". The effectiveness of<unk>  in Parkinson's disease and hyperprolactinemia is thought to be mostly due to activation of dopamine D2 receptors. While<unk>  has a similar receptor binding profile to the more well-known and chemically similar ergoline lysergic acid amide (LSD; N,N-diethyllysergamide) and acts as a partial agonist of the serotonin 5-HT2A receptor likewise, it lacks the psychedelic effects of LSD. Research suggests that the lack of psychedelic effects with<unk>  arises from biased agonism of the 5-HT2A receptor. Stimulation of the 5-HT2A protomer within the 5-HT2A–mGlu2 receptor complex evokes psychedelic effects, while these effects do not occur during sole stimulation of monomeric 5-HT2A receptors. Accordingly, different G proteins are involved.<unk>  behaves as an agonist at the 5-HT2A receptor monomer. Since it competitively antagonizes the effects of LSD, it may be regarded as a protomer antagonist of the 5-HT2A–mGluR heteromer. GPCR oligomers are discrete entities and usually possess properties distinct from their parent monomeric receptors.<unk>  dose-dependently suppresses prolactin levels due to its dopaminergic activity. As an antagonist of the 5-HT2B receptor,<unk>  has no risk of cardiac valvulopathy in contrast to related ergolines like pergolide and cabergoline. + Site Affinity (Ki nM) Efficacy (Emax %) Action D1 65 ? ? D2S 0.34 55 Partial agonist D2L 0.66 21 Partial agonist D3 0.28 49 Partial agonist D4 4.6 32 Partial agonist D5 3.5 ? ? 5-HT1A 0.15 98 Full agonist 5-HT1B 19 85 Partial agonist 5-HT1D 0.98 81 Partial agonist 5-HT2A 2.8 52 Partial agonist 5-HT2B 1.3 0 Silent antagonist 5-HT2C 6.6 75 Partial agonist α1A 5.5 0 Silent antagonist α1B 17 ? ? α1D 3.0 ? ? α2A 0.055 0 Silent antagonist α2B 0.13 0 Silent antagonist α2C 0.13 0 Silent antagonist α2D 0.79 ? ? β1 68 ? ? β2 7.9 ? ? H1 35 ? Partial agonist M1 >10,000 – – Notes: All receptors are human except α2D-adrenergic, which is rat (no human counterpart). Pharmacokinetics Absorption of<unk>  from the gastrointestinal tract with oral administration is complete. The absolute bioavailability of<unk>  is 10 to 20% due to high first-pass metabolism. The plasma protein binding of<unk>  is 60 to 70%. Peak levels of<unk>  occur 60 to 80 minutes after ingestion with high variability between individuals. The elimination half-life of<unk>  is approximately 2 hours. This is shorter than most other dopamine agonists.<unk>  has more than 15 known metabolites.
Lisuride
Miglitol
Geritol
Paricalcitol
Glibenclamide
Canagliflozin
Rosiglitazone
Glucuronide