Respiratory Effects of Amifostine and DRDE-07: Probable Prophylactic Agents of Sulphur Mustard in Rats

Abstract

Amifostine (S-2[3-aminopropylamino]ethyl phosphorothioate) and one of its analogues,
DRDE-07 (S-2[2-aminoethylamino]ethyl phenyl sulphide) are promising prophylactic agents for
sulphur mustard (SM; a blistering agent) toxicity. When given orally, DRDE-07 was more effective
than amifostine as a prophylactic agent against SM administered percutaneously. Various
pharmacological and toxicological studies are required before the introduction of a chemical as
a drug. The respiratory effects of amifostine and DRDE-07 were carried out in rats using a body
plethysmograph fitted with a volumetric pressure transducer for sensing the respiratory flow
signals. The signals were amplified, digitised, and stored on a personal computer for further
analysis. After taking control recordings of respiratory signals, different doses (0.5 LD50, 1.0 LD50
and 2.0 LD50) of amifostine and DRDE-07 were administered orally (LD50 amifostine = 2262 mg/
kg; DRDE-07 = 1599 mg/kg), and the respiratory changes were monitored for 4 h. Amifostine and
DRDE-07 showed a uniform breathing pattern even in 2.0 LD50 dose. However, a significant dosedependent
decrease in respiratory frequency was observed following amifostine administration.
DRDE-07 did not show any significant change. The tidal volume was not altered significantly
both in amifostine and DRDE-07 administered animals. The study shows that DRDE-07, even in
lethal doses, may not affect the respiration immediately, whereas, amifostine may decrease the
respiratory frequency.