effect of α-adrenergic blockers on naloxone-binding in braiN (original) (raw)

In several recent studies, we have shown that a-adrenergic blocking agents possess a degree of antinociceptive activity themselves, markedly increase morphine's analgetic and toxic effects, and effectively suppress the expression of the narcotic withdrawal syndrome in the rat (1,2,3). Since B-adrenergic blocking agents and numerous other agents possessed none of these properties, these data suggest that the narcotics and a-adrenergic blockers may be closely related. However, since all of the data up to the present are indirect, we cannot rule out the possibility that the interaction we have observed between these two classes of drugs merely represents the summation of two totally independent processes. The purpose of the studies described in this paper was to obtain more direct evidence of an interaction between morphine and a-adrenergic blocking agents. Pert and Synder (4,5) previously have demonstrated that stereospecific binding of naloxone occurs in rat brain homogenates and that various narcotic agonists and antagonists effectively reduce naloxone-binding. We have employed this preparation to examine whether a-adrenergic blockers would displace naloxone from the so-called "opiate receptor."