Methadone binding at nonopiate receptor binding sites

The binding of 3H-methadone to rabbit brain synaptosomes was studied. Binding was saturable at methadone concentrations below 10(-6)M and unsaturable above 10(-6)M. Except at high 3H-methadone concentrations, only a small fraction of the specific saturable binding of methadone was blocked by levorphanol, naloxone or morphine, suggesting that much of the saturable binding of methadone to rabbit synaptosomes is not binding at the opiate receptor. At low methadone concentrations, stereospecific methadone binding to the opiate receptor is essentially undetectable as determined by displacement with levorphanol and dextrorphan. Experiments with preparations from beef caudate, on the other hand, indicate that a larger percentage of the methadone bound to this preparation is bound to the opiate receptor but that some specific binding is also at other sites.