Abstract
Abstract
S-2-(3-Methylaminopropylamino)ethylphosphorothioic acid (WR-3689) is a radioprotective agent that is behaviorally toxic at radioprotective doses. It was recently reported that the combination of WR-3689 and caffeine ameliorated behavioral toxicity (determined by locomotor activity in mice) compared with WR-3689 alone. Since catecholamines can modulate locomotor activity, we determined norepinephrine (NE) and dopamine (DA) content (using high-performance liquid chromatography) in the hypothalamus of mice after treatment with WR-3689, caffeine, and the combination of the two drugs. CD2F1 male mice were injected intraperitoneally with saline (control), WR-3689 (100 and 200 mg/kg), caffeine (20 and 40 mg/kg), or the combination of WR-3689 (200 mg/kg) and caffeine (40 mg/kg). Control values for NE and DA ranged between 200 and 220 pg/mg and 69 and 94 pg/mg of hypothalamic tissue, respectively. WR-3689 had no effect on the content of NE and DA. In contrast, NE increased to (mean ± SE) 324 ± 27 pg/mg and 377 ± 61 pg/mg (P < 0.05) 4 hr after injections of 20 and 40 mg/kg of caffeine, respectively. Similarly, DA increased to 142 ± 13 pg/mg (P < 0.05) 4 hr after injection of 40 mg/kg of caffeine. The combination of WR-3689 and caffeine had no effect on NE and DA contents when compared with control values. These results suggest that WR-3689 can affect catecholamine metabolism in the mouse hypothalamus, but the mode of action is not clear.
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