Affinity of Various Compounds for Benzodiazepine Binding Sites in Rat Brain, Heart and Kidneys in Vitro

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Abstract
Binding of several psychoactive, antiinflammatory, antihypertensive, and antiarrhythmic drugs to central and peripheral benzodiazepine (BZ) binding sites was studied in the brain, heart and kidneys of rats. Diazepam exhibited the highest affinity for all binding sites (Ki values at 0.01 μM level); another 1,4-BZ, oxazepam, had markedly lower affinity for peripheral binding sites (Ki 21–37 μM). Non-BZ compounds had low affinity for central BZ receptors; proquazone was the most potent (Ki 9.5 μM). The affinities of non-BZ compounds were higher for peripheral BZ binding sites. The Ki value for proquazone was approximately 0.1 μM; and many other antiinflammatory agents, and the vasodilators cyclandelate and nifedipine, produced Ki values in the micromolar level. β-Blocking drugs, and several other antihypertensive and antiarrhythmic agents lacked affinity for both central and peripheral BZ binding sites. According to the results, the affinity for peripheral binding sites is independent of an affinity for central BZ receptors. Non-BZ compounds that bound to brain BZ receptors bound with equal affinity to both BZ1 and BZ2 subgroups of receptors. The compounds with affinity for peripheral BZ binding sites did not select between heart and kidneys, which suggests that these organs have similar binding sites. The role of the peripheral BZ binding sites has not yet been established. The findings of this study allow the selection of a more varied group of ligands to be used when investigating the physiological significance of these binding sites.