The specificity of binding of the narcotic agonist etorphine in synaptic membranes of rat brain in vivo.

When 3H-etorphine was administered to rats in a pharmacologically effective dose (0.75 mug/kg intracisternally), the labeled drug was concentrated in synaptic membrane fractions isolated from the brains of rats killed 10 min after etorphine injection. Pretreatment of the animals with the narcotic antagonists naloxone, diprenorphine or l-cyclorphan, blocked the pharmacological responses to etorphine and reduced 3H-etorphine binding in the membrane fractions. The differences between 3H-etorphine bound in synaptic membranes of rats treated with d-cyclorphan (inactive isomer) and l-cyclorphan (active antagonist) were in the same range as the reductions in etorphine binding in antagonist-treated rats, indicating that stereospecific and pharmacologically-specific binding sites in synaptic membranes in vivo were of the same magnitude: about 0.04 pmol/g brain.