Mechanism of action<unk> 's R-enantiomer is an agonist of both D1 and D2 dopamine receptors, with higher activity at D2. The members of the D2 subfamily, consisting of D2, D3, and D4 receptors, are inhibitory G protein–coupled receptors. The D4 receptor in particular is an important target in the signaling pathway, and is connected to several neurological disorders. Shortage or excess of dopamine can prevent proper function and signaling of these receptors leading to disease states.<unk>  improves motor function by activating dopamine receptors in the nigrostriatal pathway, the limbic system, the hypothalamus, and the pituitary gland. It also increases blood flow to the supplementary motor area and to the dorsolateral prefrontal cortex (stimulation of which has been found to reduce the tardive dyskinesia effects of L-DOPA). Parkinson's has also been found to have excess iron at the sites of neurodegeneration; both the R- and S-enantiomers of<unk>  are potent iron chelators and radical scavengers.<unk>  also reduces the breakdown of dopamine in the brain (though it inhibits its synthesis as well). It is an upregulator of certain neural growth factors, in particular NGF but not BDNF, epigenetic downregulation of which has been associated with addictive behaviour in rats.<unk>  causes vomiting by acting on dopamine receptors in the chemoreceptor trigger zone of the medulla; this activates the nearby vomiting center. Pharmacokinetics While<unk>  has lower bioavailability when taken orally, due to not being absorbed well in the GI tract and undergoing heavy first-pass metabolism, it has a bioavailability of 100% when given subcutaneously. It reaches peak plasma concentration in 10–60 minutes. Ten to twenty minutes after that, it reaches its peak concentration in the cerebrospinal fluid. Its lipophilic structure allows it to cross the blood–brain barrier.<unk>  possesses affinity for the following receptors (note that a higher Ki indicates a lower affinity): + Dopamine Receptor Ki (nM) Action D1 484 (partial) agonista D2 52 partial agonist (IA = 79% at D2S; 53% at D2L) D3 26 partial agonist (IA = 82%) D4 4.37 partial agonist (IA = 45%) D5 188.9 (partial) agonista aThough its efficacies at D1 and D5 are unclear, it is known to act as an agonist at these sites. + Serotonin Receptor Ki (nM) Action 5-HT1A 2,523 partial agonist 5-HT1B 2,951 no action 5-HT1D 1,230 no action 5-HT2A 120 antagonist 5-HT2B 132 antagonist 5-HT2C 102 antagonist + Norepinephrine/Epinephrine Receptor Ki (nM) Action α1A-adrenergic 1,995 antagonist α1B-adrenergic 676 antagonist α1D-adrenergic 64.6 antagonist α2A-adrenergic 141 antagonist α2B-adrenergic 66.1 antagonist α2C-adrenergic 36.3 antagonist It has a Ki of over 10,000 nM (and thus negligible affinity) for β-adrenergic, H1, and mACh.<unk>  has a high clearance rate (3–5 L/kg/hr) and is mainly metabolized and excreted by the liver. It is likely that while the cytochrome P450 system plays a minor role, most of<unk> 's metabolism happens via auto-oxidation, O-glucuronidation, O-methylation, N-demethylation, and sulfation. Only 3–4% of the<unk>  is excreted unchanged and into the urine. The half-life is 30–60 minutes, and the effects of the injection last for up to 90 minutes. Toxicity depends on the route of administration; the LD50s in mice were 300 mg/kg for the oral route, 160 mg/kg for intraperitoneal, and 56 mg/kg intravenous.
Apomorphine
Desomorphine
Tripelennamine
Droperidol
Tropisetron
Amfepramone
Benzatropine
Bremazocine