EVIDENCE FOR DIRECT INTERACTION OF KETAMINE WITH α‐ AND β2‐ADRENOCEPTORS

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Abstract
1. Ketamine has a number of effects that suggest that it may interact with α- and β-adrenoceptors. To date, the experimental evidence for this has been indirect and has been based on physiological studies using competitive blocking agents. In the present study we sought to determine from receptor binding studies whether ketamine binds directly to α- and β-adrenoceptors. 2. Membrane preparations o. α1- and β2-adrenergic binding sites were obtained from urinary bladder and urethrae of sheep. These binding sites were characterized by saturation analyses using [3H]-prazosin for α1-adrenoceptor binding sites and [125I]-cyanopindolol (CYP) for the β2-adrenoceptor binding sites. The receptors were further characterized by displacement studies using selective and non-selective antagonists. 3. Studies in which ketamine was used to displac. [3H]-prazosin revealed a Kd of 3.40±1.23× 10−3 mol/L for ketamine binding to ai-adrenoceptors. Displacement studies of [125I]-CYP by ketamine showed a Kd of 0.35±0.03× 10−3 mol/L for ketamine binding to β2-adrenoceptors. 4. We conclude that ketamine interacts directly with both ai- an. β2-adrenoceptors and that such interactions probably explain the reported effects of this agent on the vasculature and the bronchial tree.