The abuse of sedative-hypnotics constitutes a major drug abuse problem in the United States. It is estimated that approximately 4 percent of the adult population is involved in the non-medical use of hypnotics, with barbiturates being involved in 66 percent of the cases. The abuse liability of a compound is in part determined by the direct behavioral effects of the compound, by the stimulus properties it produces, by its reinforcing properties, and by the degree of tolerance development. To date most of the information gathered on the abuse potential of barbiturates has used racemic mixtures, and little information is available on the contribution of each of the stereoisomers to the measured effect of the racemic mixture. This is true in spite of documented differences in anesthetic potency, lethality, and in some cases, direction of pharmacological effect for stereoisomers of barbiturates. The goal of this project is to determine the contribution of each of the stereoisomers of pentobarbital, secobarbital, and hexobarbital to the abuse potential of the racemic mixture. To achieve this objective, the direct behavioral effect of each isomer will be determined under a multiple fixed-ratio, fixed-interval schedule of reinforcement, and under a punishment schedule in mice, rats and pigeons, and on spontaneous motor activity in mice and rats. The stimulus properties of each isomer and the degree of stimulus generalization will be determined in pigeons and rats. The reinforcing stimulus properties of each isomer will be determined in rats. Finally, the degree of tolerance development will be determined for each isomer in rats and pigeons. It is hoped that knowledge of the effects of the isolated stereoisomers will provide valuable data which will enable the scientific community to arrive at a better understanding of barbiturate abuse.
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| Wenger, G R; Donald, J M; Cunny, H C (1986) Stereoselective behavioral effects of the isomers of pentobarbital and secobarbital in the pigeon. J Pharmacol Exp Ther 237:445-9 |
