Substituted Amphetamine Derivatives. I. Effect on Uptake and Release of Biogenic Monoamines and on Monoamine Oxidase in the Mouse Brain

The effects of amphetamine (A), 2-, 3- and 4-chloroamphetamine (CA), 4-methylamphetamine (MA) and chlorphentermine (CP) in inhibiting the accumulation and in evoking release of radioactive labelled noradrenaline (NA), dopamine (DA) and 5-hydroxytryptamine (5-HT) and in inhibiting the oxidative deamination of tyramine and 5-HT in mouse brain slices (midbrain and striatum) were examined. The inhibitory potencies on the NA uptake in vitro and after intraperitoneal administration varied only slightly, 3-CA being the most potent and 2-CA the least active compound. The structure activity for inhibition of the DA uptake in striatal slices was similar with the exception that CP was the least potent agent. The accumulation of 5-HT was most potently inhibited by the 4- and 3-substituted amphetamines. Only a small (20 %) fraction of the 3H-NA accumulated in the midbrain slices could be released by the amphetamines but a significant release was obtained at rather low concentrations (5 × 10-7 M). The release of radioactive DA and 5-HT from striatal slices was much more pronounced and the orders of activities were similar to those for the inhibition of the accumulation of DA and 5-HT, except that CP was comparatively less active in releasing 5-HT. The oxidative deamination of tyramine and 5-HT was most potently inhibited by 4-CA and 4-MA and this effect was obtained at the same doses producing inhibition of the amine uptake. No effect was obtained on the deamination of phenethylamine.