Effects of S-2-(3-Methylaminopropylamino)ethyl Phosphorothioic Acid (WR-3689),Alone or Combined with Caffeine, on Catecholamine Content of Mouse Hypothalamus

摘要

S-2-(3-Methylaminopropylamino)ethylphosphorothioic acid (WR-3689) is aradioprotective 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), or the combination of WR3689 (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