Effects of soman and its antidotes on tracheal mucociliary transport of ferrets.
The purpose of this study was to examine the role of acetylcholinesterase on mucociliary transport by use of a potent anticholinesterase agent, soman, and potential antagonists, atropine (muscarinic antagonist) and pralidoxime (acetylcholinesterase reactivator). Initial measurements of mucociliary transport rate were obtained in anesthetized ferrets at 30-min intervals for 5.5 h. These rates remained constant at a mean of 18.2 +/- 1.0 (SE) mm/min. We studied the effects of intravenously administered soman (1-8 micrograms/kg) and observed a dose-related change in the rate of mucociliary transport [-1.1 +/- 2.7 (SE) mm/min after 1 microgram/kg, 9.8 +/- 2.9 mm/min after 5 micrograms/kg, and 14.4 +/- 4.3 mm/min after 8 micrograms/kg of soman]. Pretreatment with atropine completely prevented the response to soman, whereas pretreatment with pralidoxime did not significantly alter the response. We postulate that soman's effect on mucociliary transport relates directly to its cholinergic activity. Failure of pralidoxime to inhibit the effects of soman may relate to pralidoxime's inability to reactivate acetylcholinesterase successfully.
Marin
M G
MG
Department of Medicine, University of Rochester School of Medicine and Dentistry, New York 14642.
Zwierzynski
D
D
McBride
R K
RK
Culp
D J
DJ
D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D005289:Ferrets; D006339:Heart Rate / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D008297:Male; D009079:Mucociliary Clearance / Q000187:drug effects*; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D011220:Pralidoxime Compounds / Q000494:pharmacology*; D012016:Reference Values; D012999:Soman / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects / Q000502:physiology*
D002801:Cholinesterase Reactivators; D011220:Pralidoxime Compounds; D002245:Carbon Dioxide; D001285:Atropine; D012999:Soman; C028797:pralidoxime; D010100:Oxygen