IMPLEMENTATION OF A RADIORECEPTOR ASSAY FOR DEXMEDETOMIDINE

We have implemented a radioreceptor assay for dexmedetomidine, a novel alpha(2)-adrenoceptor agonist. Receptor-bearing membranes were prepared From rat cerebral cortex and H-3-clonidine, 4 nM, was used as the labeled ligand. Dexmedetomidine displaced 3H-clonidine in a linear fashion over a concentration of 2 x 10(-10) to 2 x 10(-8) M. The detection limit of dexmedelomidine (i.e. 10% of radiolabeled ligand displaced) in this assay was 50 pg.ml(-1) which is comparable to that seen with the reference method which utilizes gas chromotography with mass spectrometer (GC/MS) in series (Vuorilehto et al. 1989). Endogenous catecholamines, which can displace the radiolabeled ligand from its binding site, could easily be eliminated with a one-step extraction procedure. A comparison was made with the reference method (GC/MS) in 47 human plasma samples; the correlation coefficient (r(2)) was 0.61 (P < 0.001). The radioreceptor assay was also successfully applied for determining dexmedetomidine concentration in rabbit samples. These data indicate that the radioreceptor assay can be utilized for characterizing the pharmacokinetics of novel alpha(2) agonists which are now being introduced into the clinical practice of anaesthesia.