New Dopamine D2 Receptor Agonist, [3H]MCL-536, for Detecting Dopamine D2high Receptors in Vivo
| Autor: | Philip Seeman, Sivan Subburaju, Anna W. Sromek, John L. Neumeyer |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Agonist Apomorphine Physiology medicine.drug_class Dopamine Cognitive Neuroscience Binding Competitive Biochemistry Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Dopamine receptor D2 medicine Animals Aporphine Receptor Raclopride Receptors Dopamine D2 Chemistry Antagonist Cell Biology General Medicine Ligand (biochemistry) Corpus Striatum 030104 developmental biology Dopamine Agonists Schizophrenia Biophysics Dopamine Antagonists 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | ACS Chem Neurosci |
| ISSN: | 1948-7193 |
| DOI: | 10.1021/acschemneuro.8b00096 |
| Popis: | Increases in the D2 receptor high affinity state are associated with certain neurological disorders. We synthesized and characterized the high-affinity D2high ligand [(3)H]MCL-536 in competition binding against the D2/3 agonist R-(−)-N-n-propylnorapomorphine (NPA) and the D2/3 antagonist raclopride. The total binding of [(3)H]MCL-536 (minus that in the presence of 100 nM NPA) was measured by saturation binding in CHO cells expressing human D2long; the data yielded separable, nonsaturable nonspecific, and saturable specific components. The former represents an aporphine site common to NPA and [(3)H]MCL-536. The latter indicated specific binding to the total D2 receptors (both high and low-affinity states). [(3)H]MCL-536 had a K(d) of 0.8 nM. In competition binding, NPA had a K(i) of 0.16 nM, and a K(i) of 0.9 nM for raclopride. Co-incubation with guanylylimidodiphosphate abolished binding to D2high. This unique profile makes radiolabeled MCL-536 a versatile tool for diagnostics and therapeutics, and may quantify D2high sites in schizophrenia and PD patients in vivo. |
| Databáze: | OpenAIRE |
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