Design and interpretation of opiate antagonist trials in XXXX .

@entity1510 @entity1 @entity303
In view of the reports of possible beneficial effects of @entity1510 in @entity303 , rationales and strategies for studying endogenous opiate systems are reviewed. Important considerations in the design and interpretation of clinical investigations using @entity1510 are also reviewed. The nature and distribution of endogenous opiate systems are summarized from an historical perspective. Endogenous opiate systems are distributed throughout the central nervous system and play important roles in a variety of brain functions, including memory and learning. In view of this, several rationales are evident for studying endogenous opiate systems in @entity303 , since it is a syndrome in which structures known to contain opiate systems are disturbed, functions modulated by opiate systems are disturbed, and other neurotransmitter systems (functionally linked to endogenous opiate systems) are disturbed. Different strategies for studying endogenous opiate systems are reviewed, including examination of body fluids and pharmacologic challenge studies. @entity1510 , a competitive opiate receptor antagonist, is a commonly used pharmacologic agent. The design of a multidose @entity1510 study of 12 @entity303 @entity1 is discussed, with reference to the pharmacokinetics, pharmacodynamics, and specificity of @entity1510 as well as to the nature of the dependent measures selected for this study. No cognitive benefit was observed in this study. Behavioral arousal was observed at @entity1510 doses, with more evident psychomotor retardation at higher doses. These findings are contrasted with the results of @entity1510 challenges in other studies. The varying effects of @entity1510 within and across populations can be conceptualized in terms of the basic and clinical considerations previously discussed. The importance of dose-finding studies is stressed for this and other drug trials.
