Binding of opiates and endogenous opioid peptides to neuroleptic receptor sites in the corpus striatum

Abstract

Some opiates with morphinan- and benzomorphan-structures possess affinities for neuroleptic receptors as revealed by their abilities to compete with 3H-spiroperidol for common binding sites in rat striatum in vitro (IC 50 in the range between 10 −6 and 10 −5M). The binding of these opiates to neuroleptic receptors appears to be of pharmacological significance, since in vivo studies in mice revealed a small but significant displacement of spiroperidol by high doses of the opiate antagonist levallorphan from specific binding sites in the striatum. In addition, there exists some correlation between the ability of opiates to bind to neuroleptic receptor sites in vitro and their potency to evoke “bizarre behavior” in rats in vivo . In contrast, a wide variety of other opiates having morphine-, morphinone- or oripavine-structure showed no affinity for neuroleptic binding sites in vitro (IC 50 greater than 10 −4 M). Of the opioid peptides (methionine-enkephalin, leucine-enkephalin and β-endorphin) none has an affinity for neuroleptic binding sites. A variety of other peptides were also investigated but did not interfere with spiroperidol binding. Only ACTH showed a moderate affinity for neuroleptic binding sites.