Congrès annuel SFT - Paris, 23-24 octobre 2006
"Toxicologie de la pharmacodépendance aux médicaments et aux drogues" Les recommandations de l'Agence européenne d'évaluation des médicaments pour l'évaluation non clinique du potentiel de pharmacodépendance Dr. Leon A.G.J.M. van Aerts Dependence potential of a substance is the propensity of a substance, as a consequence of its pharmacological effects on physiological or psychological functions, to give rise to a need for repeated doses of the substance to “feel good” or to avoid “feeling bad.” Dependence potential is determined by those intrinsic pharmacological properties that can be measured in animal and human drug testing procedures. This guideline introduces a two-tiered approach to investigate the dependence potential of new CNS active substances. In the first tier, studies reveal the pharmacological profile of the substance. Based on data from the first tier and other early indicators it should be decided whether subsequent behavioural studies investigating the reinforcing properties and potential to cause withdrawal phenomena is necessary. The guideline indicates which type of studies is needed and describes the minimum requirements of such studies, but a flexible approach is allowed, based on the type of substance that is investigated. Reinforcing properties and physical withdrawal phenomena are well-known aspects of dependence potential. However, other aspects of withdrawal which are less clear by plain clinical observation, as exemplified by selective serotonin re-uptake inhibitors (SSRIs), also need to be evaluated. The relevance of the data for the assessment of human safety with respect to dependence potential of a medicinal drug substance should be discussed. Key words : dependence potential, guideline, reinforcing properties, withdrawal syndrome |
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