Abuse liability studies of opioid agonist-antagonist in humans

FRANÇAIS :
Les prévisions du potentiel addictif d'un médicament avant sa mise en vente se compliquent du fait que de nombreux facteurs influencent l'usage toxicomaniaque. L'article passe en revue, de façon détaillée, les méthodes de laboratoire permettant d'évaluer ce potentiel addictif des opiacés : mesure des effets subjectifs, auto-administration, méthode discriminatoire, évaluation de la dépendance physique, étude du sevrage par des antagonistes, méthodes de substitution. Les résultats d'études comparatives sont présentés et discutés pour la pentazocine, le butorphanol, la nalbuphine et la buprénorphine
ENGLISH :
Prediction of abuse liability of a drug before it reaches the market is complicated by the fact that there are many factors that influence the actual abuse of a drug. Laboratory methods used in humans to assess the abuse liability of the opioids are reviewed and illustrative studies of morphine and the agonist-antagonist opioids, pentazocine, butorphanol, nalbuphine and buprenorphine, are presented. Three assesment methods, subjective effect measurement, self-administration and drug discrimination , provide information relevant to measuring reinforcing efficacy, a major determinant of the degree to which a drug is sought and self-administered by abusers. Physical dependence capacity, which can contribute to sustained drug use, is evaluated in direct addiction and substitution / suppression studies. Withdrawal precipitation studies measure antagonist activity which might limit abuse. The results of testing the agonist-antagonist opioids are generally consistent accross these various methods and consistent with historical experience with these drugs, suggesting that these methods are useful in predicting abuse liability of novel opioids. (Author's abstract)