Relationship between radioprotective and neuromotor effects of S-2(3-aminopropyl-amino)ethylphosphorothioate (WR-2721) in mice.
The radioprotective and neuromotor effects of WR-2721 were studied in male albino ICR strain mice. The protective activity was evaluated by graded doses of WR-2721 (50-400 mg/kg, IP) against whole body 60Co gamma irradiation at a single maximal lethal threshold dose rad (i.e., 1250 rad). The neuromotor effects of the drug were assayed by its action, at the same dose range as used in the protection assay, on spontaneous motor activity (SMA) and wire hanging performance (WHP). Drug doses were administered 30 min before radiation exposure and neurobehavioral testings. The results showed a dose-dependent increase in radioprotection and an inhibition in the neuromotor tasks. The radioprotective efficacy was seen at doses at which intrinsic neuromotor deficits were detected (100-400 mg/kg). A dose-related parallelism of protective efficacy and neurobehavioral toxicity (i.e., SMA inhibition and WHP disruption) was also observed. The present findings suggest that WR-2721 induces neuromotor dysfunctions along with its radioprotectivity.
Liu
W F
WF
Laboratory of Behavioral Pharmacology and Toxicology, Fourth Research Department CSIST, Taiwan, Republic of China.
Shih
J H
JH
Liu
R F
RF
Ma
C
C
Lin
C H
CH
Liu
C Y
CY
Chang
C L
CL
Wu
M T
MT
D004999:Amifostine / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects*; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D011837:Radiation-Protective Agents
D009946:Organothiophosphorus Compounds; D011837:Radiation-Protective Agents; D004999:Amifostine