Opiate receptor identification in vitro and in vivo

Using tritiated opiates with a high specific radioactivity, a high affinity binding to brain homogenates has been observed in vitro. Strong evidence was given that this type of binding is due to the interaction of labelled opiates with their specific receptors in the brain, since the ability of a wide variety of opiates to inhibit this binding corresponds very well with the potency of the drugs to produce their pharmacological effects in vivo. We have found that the simultaneous injection of labelled opiates into animals together with high doses of nonradioactive opiates decreases the brain concentration of the labelled drug. This displacement from brain satisfies criteria similar to those used for the identification of the opiate receptor in vitro. Furthermore, opiates produce their pharmacological effects in the same dose range in which they are able to displace a radiolabelled opiate from the brain. This strongly suggests that the receptor occupation by opiates can be identified by concentration changes in the brain of living animals.