Effects of S-2-(3-methylaminopropylamino)ethyl phosphorothioic acid (WR-3689), alone or combined with caffeine, on catecholamine content of mouse hypothalamus.
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.
Department of Radiation Biochemistry, Armed Forces Radiobiology Research Institute, Bethesda, Maryland 20889-5603.
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D004999:Amifostine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism*; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000494:pharmacology*
D011837:Radiation-Protective Agents; C049344:S-2-(3-methylaminopropylamino)ethylphosphorothioic acid; D002110:Caffeine; D004999:Amifostine; D004298:Dopamine; D009638:Norepinephrine