Influence of formamidines on biogenic amine levels in rat brain and plasma

Biogenic amine levels in samples of whole brain and plasma following treatment of rats with chlordimeform (CDF), its two N-demethyl metabolites (DMC and DDC), p-chloroamphetamine (PCA), and harmaline were separated by high performance liquid chromatography equipped with fluorescence or electrochemical detection systems. At 1 hr following s.c. injection, CDF (200 mg/kg) caused a reduction in levels of norepinephrine (NE), 5-hydroxytryptamine (5-HT), and tyramine (TRM), an increase in dopamine (DA), and no change in levels of beta-phenethylamine (PEA) in samples of whole rat brain, whereas DMC (100 mg/kg) and DDC (25 mg/kg) effected reductions of brain levels of NE, 5-HT, TRM, and PEA with no change in DA. The effect of DMC (100 mg/kg) on NE and DA levels in brain was followed periodically for 24 hr. Following a significant decrease at 1 hr, NE levels increased to a maximum at 12 hr and remained higher than controls throughout the remainder of the 24 hr test period. DA levels increased during the initial 12 hr and remained significantly higher than controls for the remaining 12 hr. The influence of s.c. vs i.p. administration of DMC (100 mg/kg) on brain amine levels was examined. Intraperitoneal treatment generally resulted in lower amine levels in DMC and vehicle treated animals. Differences in treatment effects were similar for all amines except for 5-HT in which s.c. injection produced a slight reduction, while i.p. injection resulted in a two-fold increase.(ABSTRACT TRUNCATED AT 250 WORDS)