The discriminative stimulus effects of naloxone and naltrexone in morphine-treated rhesus monkeys: comparison of oral and subcutaneous administration.
BACKGROUND
Opioid antagonists are used to reverse the toxic effects of opioids, to diagnose opioid dependence and to treat opioid and other (alcohol) drug abuse.


OBJECTIVE
This study compared the discriminative stimulus effects of two opioid antagonists (naloxone and naltrexone), after parenteral and oral administration.


METHODS
The discriminative stimulus effects of naloxone and naltrexone were evaluated every 15 min over a 2-h period in four morphine-treated (3.2 mg/kg per day) rhesus monkeys discriminating between subcutaneous (SC) injections of naltrexone (0.01 or 0.032 mg/kg) and saline, while responding under a fixed-ratio 5 schedule of stimulus shock termination.


RESULTS
Within 15 min of SC administration, naloxone and naltrexone produced greater than 90% drug-appropriate responding at doses of 0.032 and 0.01 mg/kg, respectively. The largest dose of naloxone (3.2 mg/kg) administered orally produced 82% drug-appropriate responding within 90 min; the same dose of naltrexone administered orally produced greater than 90% drug-appropriate responding within 30 min. Although both drugs were at least 100-fold more potent when administered SC, as compared to orally, there was little difference (3-fold) between the potency of naloxone and naltrexone by either route.


CONCLUSIONS
These results fail to support the view that naloxone has reduced bioavailability after oral administration, as compared to naltrexone, or that its pharmacokinetic profile is particularly advantageous for some therapeutic settings (e.g. Talwin Nx).
Department of Pharmacology, Louisiana State University Medical Center, New Orleans 70112, USA.
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Gauthier
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France
D000818:Animals; D004193:Discrimination Learning / Q000187:drug effects*; D005260:Female; D008253:Macaca mulatta; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000008:administration & dosage* / Q000494:pharmacology; D009271:Naltrexone / Q000008:administration & dosage* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage* / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*
D009292:Narcotic Antagonists; D009294:Narcotics; D009270:Naloxone; D009271:Naltrexone; D009020:Morphine