title: Determination of dexmedetomidine in rat plasma by a sensitive [3H]clonidine radioreceptor assay.
abstract: This paper describes the development and implementation of a sensitive radioreceptor assay (RRA) for determining concentrations of dexmedetomidine, an alpha-2 adrenergic agonist with anesthetic properties, in rat plasma. Calf retina membranes were selected as the alpha-2 adrenergic receptor source, and the alpha-2 antagonist [3H]RX821002 and the alpha-2 agonist [3H]clonidine were evaluated as radioligands. We optimized the binding conditions for both radioligands and chose a radioligand for implementation in the RRA based on the characteristics of the inhibition binding curves with dexmedetomidine. The final method is based on competition between the radioligand [3H]clonidine and dexmedetomidine for high-affinity binding sites present in calf retina membranes. The assay has a coefficient of variation of 8% in the range 23.7-592 pg for 0.2 mL of plasma. This assay can be applied to pharmacokinetic-pharmacodynamic studies of dexmedetomidine.
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, CA, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Bol
authors.forename: A P
authors.initials: AP
authors.lastname: IJzerman
authors.forename: M
authors.initials: M
authors.lastname: Danhof
authors.forename: J W
authors.initials: JW
authors.lastname: Mandema
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000097:blood* / Q000378:metabolism; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D003000:Clonidine / Q000378:metabolism*; D019329:Idazoxan / Q000031:analogs & derivatives / Q000378:metabolism; D007093:Imidazoles / Q000097:blood* / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008345:Manganese / Q000494:pharmacology; D020926:Medetomidine; D008566:Membranes / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D015203:Reproducibility of Results; D012160:Retina / Q000378:metabolism; D012680:Sensitivity and Specificity; D014316:Tritium
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D014316:Tritium; D008345:Manganese; C058525:2-methoxyidazoxan; D008274:Magnesium; D003000:Clonidine; D020926:Medetomidine; D019329:Idazoxan