Failure to detect any transport of the irreversible monoamine oxidase inhibitor N-cyclopropyl-4-chloroamphetamine by the carrier of 5-hydroxytryptamine in the brain of the rat in vivo.

N-Cyclopropyl-4-chloroamphetamine (LY 93716) was examined for its potential preference for inhibiting the activity of monoamine oxidase (MAO) within serotonergic nerve terminals in the hypothalamus of the rat. Such an effect should support the hypothesis of Fuller and Perry (1977) (Neuropharmacology 16: 495-497) that this compound is transported by the uptake mechanism for 5-hydroxytryptamine (5-HT). By using a small (0.1 microM) substrate concentration of [14C]5-HT and a synaptosomal preparation incubated in the absence and presence of a selective inhibitor of the uptake of 5-HT (citalopram) it is possible to measure the activity of MAO in serotonergic nerve terminals. It was found that LY 93716 caused greater inhibition outside than inside the serotonergic nerve terminals when the activity of MAO was analysed 24 hr after the injection, but an inverted relationship was observed when analysed 72 hr after administration. Inhibition of uptake did not cause any change in the inhibition of MAO within the serotonergic nerve terminals at the former time but antagonized the inhibition observed 72 hr after the injection. It is concluded that the latter effect was due to antagonism of the neurotoxic action of LY 93716 and that no evidence was found that LY 93716 is transported by the uptake carrier for 5-HT.