Analyses of L-a-Acetylmethadol (LAAM) and Buprenorphine in Rhesus Monkeys Using Drug Discrimination Procedures
Cabansag, Sharon R.
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Methadone which is the current treatment for heroin detoxification and maintenance therapy has many disadvantages such as a short duration of action, addictive liability, and detoxification difficulties. To address this problem, drug discrimination was used to analyze two opioid drugs, the agonist L-a-acetylmethadol hydrochloride (LAAM) and, the partial agonist buprenorphine hydrochloride, as potential substitutes for methadone. Three morphine-treated, adult, female rhesus monkeys discriminated between subcutaneous (s.c.) injections of saline and naltrexone while responding under a fixed-ratio schedule of stimulus-shock termination. LAAM had morphine-like actions that were reversed by the antagonist naltrexone and a longer duration of action (72 hours) than methadone. The long duration of action is due to its active normetabolites and possibly the s.c. route of administration and long half-life. LAAM was demonstrated to have several disadvantages such being easily reversible and highly toxic at large doses. It appears that buprenorphine, a low efficacy agonist, may be a better agent in heroin detoxification and maintenance therapy. Buprenorphine exhibited two different actions: antagonist and agonist characteristics which was determined by the extent of the individual's dependence. The antagonist and agonist properties were difficult to reverse. Buprenorphine did not produce respiratory depression and was shown to have a longer duration of action (6 - 11 days) than LAAM (72 hours) due to buprenorphine's pseudoirreversibility. Despite the varying characteristics of buprenorphine, the kinetics of this drug were essentially the same.