COMPARATIVE EFFECTS OF dl-p-METHOXYAMPHETAMINE AND d-AMPHETAMINE ON CATECHOLAMINE RELEASE AND REUPTAKE IN VITRO

¹ Department of Pharmacology, University of California Medical Center and Langley Porter Neuropsychiatric Institute, San Francisco, California

Dl-p-Methoxyamphetamine (PMA), unlike d-amphetamine, does not induce stereotyped behaviors and is less effective than d-amphetamine in stimulating psychomotor activity. To investigate the reasons for the different behavior effects caused by PMA and d-amphetamine, a comparison was made between the effects of the two drugs on the release and reuptake of ³H-norepinephrine (NE) and ³H-dopamine (DA) in tissue slices prepared from the cerebral cortex and the corpus striatum of the rat brain. PMA was found to be equipotent to d-amphetamine in causing the release of ³H-NE from the cortex. PMA also increased the release of newly synthesized ³H-NE formed from ³H-DA in this region. However, PMA was less potent than ^d-amphetamine in causing the release of ³H-DA either taken up from the incubation medium or formed from ³H-tyrosine in the corpus striatum. PMA, as does d-amphetamine, competitively blocks the reuptake of ³H-NE and of ³H-DA into slices prepared from the cortex and corpus striatum, respectively. PMA was 14% as effective as d-amphetamine in blocking ³H-DA uptake in the corpus striatum and was 29% as effective as d-amphetamine in blocking ³H-NE uptake in the cortex. The results suggest that the relatively weak effect of PMA on catecholamine release and reuptake in structures rich in DA-containing neurons may be related to the lack of effect of PMA on locomotor activity and stereotyped behaviors.