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 prepar ed From rat cerebral cortex and H-3-clonidine, 4 nM, was used as the l abeled ligand. Dexmedetomidine displaced 3H-clonidine in a linear fash ion 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 t he reference method which utilizes gas chromotography with mass spectr ometer (GC/MS) in series (Vuorilehto et al. 1989). Endogenous catechol amines, which can displace the radiolabeled ligand from its binding si te, could easily be eliminated with a one-step extraction procedure. A comparison was made with the reference method (GC/MS) in 47 human pla sma 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 t hat the radioreceptor assay can be utilized for characterizing the pha rmacokinetics of novel alpha(2) agonists which are now being introduce d into the clinical practice of anaesthesia.