title: Behavioral toxicity of selected radioprotectors.
abstract: Effective radioprotection with minimal behavioral disruption is essential for the selection of protective agents to be used in manned spaceflight.  This overview summarizes the studies on the behavioral toxicity of selected radioprotectors classified as phosphorothioates (WR-2721, WR-3689), bioactive lipids (16, 16 dimethylprostaglandin E2(DiPGE2), platelet activating factor (PAF), leukotriene C4), and immunomodulators (glucan, synthetic trehalose dicorynomycolate, and interleukin-1).  Behavioral toxicity was examined in laboratory mice using a locomotor activity test.  For all compounds tested, there was a dose-dependent decrease in locomotor behavior that paralleled the dose-dependent increase in radioprotection.  While combinations of radioprotective compounds (DiPGE2 plus WR-2721) increased radioprotection, they also decreased locomotor activity.  The central nervous system stimulant, caffeine, was able to mitigate the locomotor decrement produced by WR-3689 or PAF.
authors.affiliation: Behavioral Sciences Department, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889-5245, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Landauer
authors.forename: H D
authors.initials: HD
authors.lastname: Davis
authors.forename: K S
authors.initials: KS
authors.lastname: Kumar
authors.forename: J F
authors.initials: JF
authors.lastname: Weiss
mesh_terms: D015064:16,16-Dimethylprostaglandin E2 / Q000633:toxicity; D000276:Adjuvants, Immunologic / Q000633:toxicity*; D004999:Amifostine / Q000031:analogs & derivatives / Q000633:toxicity; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003311:Cord Factors / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005936:Glucans / Q000633:toxicity; D007375:Interleukin-1 / Q000633:toxicity; D017997:Leukotriene C4 / Q000633:toxicity; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D010743:Phospholipids / Q000633:toxicity*; D010972:Platelet Activating Factor / Q000633:toxicity; D011837:Radiation-Protective Agents / Q000633:toxicity*; D013438:Sulfhydryl Compounds / Q000633:toxicity*
chemical_list: D000276:Adjuvants, Immunologic; D000697:Central Nervous System Stimulants; D003311:Cord Factors; D005936:Glucans; D007375:Interleukin-1; D010743:Phospholipids; D010972:Platelet Activating Factor; D011837:Radiation-Protective Agents; D013438:Sulfhydryl Compounds; C049344:S-2-(3-methylaminopropylamino)ethylphosphorothioic acid; D017997:Leukotriene C4; D002110:Caffeine; C043399:6,6'-dicorynomycolyl trehalose; D004999:Amifostine; D015064:16,16-Dimethylprostaglandin E2