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EVIDENCE FOR DIRECT INTERACTION OF KETAMINE WITH α‐ AND β 2 ‐ADRENOCEPTORS
Author(s) -
Bevan RK,
Rose MA,
Duggan KA
Publication year - 1997
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1997.tb02720.x
Subject(s) - prazosin , ketamine , binding site , chemistry , adrenergic receptor , receptor , pharmacology , medicine , endocrinology , biology , antagonist , biochemistry , anesthesia
SUMMARY 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. α 1 ‐ and β 2 ‐adrenergic binding sites were obtained from urinary bladder and urethrae of sheep. These binding sites were characterized by saturation analyses using [ 3 H]‐prazosin for α 1 ‐adrenoceptor binding sites and [ 125 I]‐cyanopindolol (CYP) for the β 2 ‐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. [ 3 H]‐prazosin revealed a K d of 3.40±1.23× 10 −3 mol/L for ketamine binding to ai‐adrenoceptors. Displacement studies of [ 125 I]‐CYP by ketamine showed a K d of 0.35±0.03× 10 −3 mol/L for ketamine binding to β 2 ‐adrenoceptors. 4. We conclude that ketamine interacts directly with both ai‐ an. β 2 ‐adrenoceptors and that such interactions probably explain the reported effects of this agent on the vasculature and the bronchial tree.