COMPARATIVE ACTIONS OF MONOMETHOXY-AMPHETAMINES ON RELEASE AND UPTAKE OF BIOGENIC-AMINES IN BRAIN-TISSUE

Abstract

P-Methoxyamphetamine (PMA), a known hallucinogen, is the most potent compound among methoxyamphetamines in disrupting behavior in rats. PMA, unlike d-amphetamine (A), did not induce stereotyped behavior and was less effective than A in stimulation of locomotor d-amphetamine-like effects, but o-methoxyamphetamine (OMA) was devoid of any locomotor stimulation. To investigate the reasons for the different behavioral effects caused by PMA, m-methoxyamphetamine (MMA), OMA and A, a comparison was made among these drugs on the release and uptake of 3H-5-hydroxytryptamine (3H-5-HT), 3H-norepinephrine (3H-NE) and 3H-dopamine (3H-DA) in tissue slices of cerebral cortex and corpus striatum of rat brain. The potencies for the increased release of 3H-5-HT were PMA > MMA .gtoreq. A > OMA in cerebral cotex, of 3H-NE in cortex, A .gtoreq. PMA = MMA > OMA, and of 3H-DA in corpus striatum, A > MMA > PMA .gtoreq. OMA. The potencies for inhibiting the uptake of 3H-5-HT in cerebral cortex and corpus striatum were found to be PMA > MMA > A > OMA and of 3H-NE in cortex A > PMA .gtoreq. MMA > OMA, and 3H-DA in corpus striatum A > MMA > PMA > OMA. d-PMA is equipotent to l-PMA in increasing the release of 3H-5-HT but is more potent than l-PMA in blocking the uptake of 3H-5-HT. The high potency of PMA on increasing the release and inhibiting the uptake of 5-HT suggests that 5-HT may be involved in the production of hallucinogenic effects of PMA.