Effects on 1,3-bis(tetrahydro-2-furanyl)-5-fluoro-2,4-pyrimidinedione(FD-1) on the central nervous system: 1. Effects on monoamines in the brain.

The effect of 1,3-bis(tetrahydro-2-furanyl)-5-fluoro-2,4-pyrimidinodione(FD-1) on the central nervous system was examined by measuring regional changes in the concentrations of its metabolites and of monoamines in the brain of rats after single or repeated doses of FD-1. After single doses of FD-1, its metabolites were found to be evenly distributed in the brain. Chronic administration of FD-1 increased the concentration of two metabolites, namely 5-fluoro-2,4-pyrimidinedione(5-FU) and gamma-hydroxybutyrate (GHB) in all parts of the brain. Single treatment with FD-1 and GHB-Na increased the concentration of dopamine (DA) in the corpus striatum; treatment with FD-1, 5-fluoro-1-(tetrahydro-2-furanyl)-2,4-pyrimidinedione(FT) or GHB-Na decreased the level of acetylcholine (ACh) in the corpus striatum; treatment with 5-FU decreased the level of 5-hydroxytryptamine in the corpus striatum and hypothalamus; treatment with FD-1, FT, 5-FU or GHB-Na decreased the level of ACh in the brain stem. It is concluded that the effects of FD-1 on the central nervous system may be mediated by GHB and/or 5-FU and are probably due to an effect on the dopaminergic neurons.