Effect of reserpine on the brain uptake of carbon 11 methamphetamine and itsN-propagyl derivative, deprenyl

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Abstract
The enantiomers of methamphetamine (MAMP) and itsN-propagyl derivative, deprenyl, were labelled with carbon 11, and the tissue distribution of these labelled compounds in mice was studied. Both enantiomers of11C-MAMP rapidly entered into the brain and then disappeared according to a single exponential curve. The enantiomers of11C-deprenyl were also rapidly distributed to various organs in the same manner. With regard to elimination, however, a stereoselective, long-term retention of radioactivity in the brain, heart and lung, due to its irreversible binding with monoamine oxidase B, was observed forl-11C-deprenyl. In reserpinized mice, the initial brain uptake of both thel andd forms of11C-MAMP was significantly decreased. On the other hand, the brain uptake of both enantiomers of11C-deprenyl was slightly increased by pretreatment with reserpine. A significant and non-stereoselective elevation of the lung uptake of11C-deprenyl was also seen in reserpinized mice. In addition, both the relative tissue distribution and ratios of radioactivity in the brain compared with blood or heart at 1 and 5 min after the injection of11C-labelled methanol in mice were not changed by reserpine. These results indicate that the transport or binding processes of these amines rather than the blood flow might be altered by reserpine. There would be an important role of the pKa values of amines in both processes. The reduction of brain uptake as well as the change in ratio between brain and heart ofl-11C-MAMP in reserpinized mice 1 min after injection were reversed by treatment with amphetamine in a dose-related manner. D-Amphetamine was found to be several times more potent than the correspondingl-form in this regard. The present results reveal some possibility that the transport or binding processes of MAMP in the brain may be regulated by cathecholaminergic neurotransmission.