STUDIES ON THE ANALGESIC ACTIVITY OF THE AMPHETAMINE ISOMERS IN MICE
Abstract
Differences in the behavioral effects of the amphetamine isomers have been well documented and are believed to stem from the differential actions of the isomers on central biogenic amine systems. The d-isomer of amphetamine is generally reported to be from 2-10 times more potent than the 1-form for most behavioral tests. However, preliminary studies from this laboratory have shown 1-amphetamine to be significantly more analgesic in mice than the d-isomer at equal doses. Using the hot plate jump latency test, a comparison of the effects of pharmacological alterations of biogenic amine systems on the analgesic activity of d-amphetamine, 1-amphetamine and morphine has been carried out. Fluoxetine and metergoline significantly abolished the analgesic effect of 1-amphetamine but enhanced the analgesic effect of morphine; no effect was seen with the d-isomer. Pretreatment with p-chlorophenylalanine had no effect on d-amphetamine, enhanced 1-amphetamine analgesia, and reduced the analgesic effect of morphine. Alpha-methyltyrosine reduced the effect of both d- and 1-amphetamine but enhanced morphine analgesia. Pimozide slightly enhanced the effect of morphine but had little effect on the amphetamine isomers, while drug interactions with propranolol were not significant. The effects of d-amphetamine and morphine were enhanced in the presence of phentolamine but this enhancement reflected the analgesic effect seen with phentolamine alone; the effect of 1-amphetamine was unchanged by phentolamine. Yohimbine increased the effect of morphine but decreased the effect of 1-amphetamine; no effect was seen with d-amphetamine. Clonidine had virtually no effect on the action of morphine or d-amphetamine, but completely blocked the action of 1-amphetamine. The results support the hypothesis that differential actions of the amphetamine isomers on brain serotonergic systems, as well as those of other biogenic amines are involved in the differential analgesic activity of the amphetamine isomers.
Degree
Ph.D.
Subject Area
Pharmacology
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