EVIDENCE FOR DIRECT INTERACTION OF KETAMINE WITH ALPHA(1) AND BETA(2)-ADRENOCEPTORS

1. Ketamine has a number of effects that suggest that it may interact with alpha- and beta-adrenoceptors. To date, the experimental evidence for this has been indirect and has been based on physiological studie s using competitive blocking agents. In the present study we sought to determine from receptor binding studies whether ketamine binds direct ly to alpha- and beta-adrenoceptors. 2. Membrane preparations of alpha (1)- and beta(2)-adrenergic binding sites were obtained from urinary b ladder and urethrae of sheep. These binding sites were characterized b y saturation analyses using [H-3]-prazosin for alpha(1)-adrenoceptor b inding sites and [I-125]-cyanopindolol (CYP) for the beta(2)-adrenocep tor binding sites. The receptors were further characterized by displac ement studies using selective and non-selective antagonists. 3. Studie s in which ketamine was used to displace [H-3]-prazosin revealed a K-d of 3.40 +/- 1.23 X 10(-3) mol/L for ketamine binding to alpha(1)-adre noceptors. Displacement studies of [I-125]-CYP by ketamine showed a K- d of 0.35 +/- 0.03 X 10(-3) mol/L for ketamine binding to beta(2)-adre noceptors. 4. We conclude that ketamine interacts directly with both a lpha(1)- and beta(2)-adrenoceptors and that such interactions probably explain the reported effects of this agent on the vasculature and the bronchial tree.