Effects of N-substituted analogs of (−)-α-acetylmethadol and (−)-α-methadol on schedule-controlled behavior

The behavior of the pigeon maintained under a variable-interval schedule of food presentation was used to compare the activity of four novel N-substituted acetylmethadol and methadol analogs with that of methadone and (-)-α-acetylmethadol (LAAM). All of the acetylmethadol and methadol analogs had narcotic agonist activity, as defined by the reversibility of their behavioral effects by naloxone. The effect of the N-substituted analogs on variable-interval responding was similar to that of methadone and LAAM, but all these compounds had a slower onset of action than methadone and a shorter duration of action than LAAM. None of the N-substituted analogs showed narcotic antagonist activity when tested against methadone.