"Scientific and technological advances of the twentieth century have fostered the ability to delineate the exact nature and structure of the active component of psychoactive compounds leading to the ability to synthesize them completely in the laboratory without requiring a plant-based compound at all. Among the first of these were the barbiturates and amphetamines, followed later by synthetic opioids, hallucinogens and "sedatives" such as the benzodiazepines (Westermeyer, 1988). "
[Show abstract][Hide abstract] ABSTRACT: Methamphetamine (METH) is a popular drug of abuse, readily synthesized in clandestine laboratories. Illicit synthesis results in various contaminants, one of which is a-benzyl-N-methylphenethylamine (BNMPA). This dissertation investigates the hypotheses that contaminants like BNMPA may contribute to the toxicity of METH and that detection of BNMPNmetabolites in biological fluids may be utilized as markers of illicit METH consumption. Based on metabolic studies of benzphetamine (a structurally similar compound), we predicted the four major metabolites of BNMPA to be N- demethyl-BNMPA, diphenyl-2-propanone, para-hydroxy-N-demethyl-BNMPA para-hydroxy-BNMPA, and diphenyl-2-propanol. We synthesized these compounds and developed a gas chromatography/mass spectrometry detection method. We confirmed these as true metabolites in humans following ingestion. para-Hydroxy-BNMPA and para-hydrnxy-N-demethyl-BNMPA (as conjugates) were the major metabolites detected.
[Show abstract][Hide abstract] ABSTRACT: Stimulant drugs have been illicitly consumed for non-medical purposes for centuries. Within the past several decades procedures for assessing the abuse liability of a compound prior to marketing have been developed, which should limit the introduction of new stimulants with high abuse liability to the public. Drugs with high abuse liability are positive reinforcers in that they maintain behavior leading to their consumption. Assessment of abuse liability has traditionally involved a comparison of the profile of effects of a known drug of abuse to that of a drug with unknown abuse liability. With respect to stimulant drugs, amphetamine and cocaine may be considered prototypic stimulants with high abuse liability. Various procedures have been used to study abuse liability including the measuring of (1) subjective effects, (2) drug 'liking', (3) estimates of value, (4) the accuracy of drug identification, (5) the ability of trained subjects to discriminate one drug from another and (6) drug self-administration. In this paper the behavioral effects of a number of stimulant drugs will be compared along these dimensions and the effects along each dimension will be related to each drugs' known abuse liability. Dissociations among the various measures will also be described, and the implications of these dissociations discussed. We conclude that the best single assessment of abuse liability is obtained from drug self-administration studies, but that the most accurate assessment of abuse liability is obtained when the effects of a drug are evaluated along as many of these dimensions as possible.
Drug and Alcohol Dependence 07/1991; 28(1):3-48. DOI:10.1016/0376-8716(91)90052-Z · 3.42 Impact Factor
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