Effectiveness of Physostigmine as a Pretreatment Drug for Protection of Rats from Organophosphate Poisoning

Effectiveness of Physostigmine as a Pretreatment Drug for Protectionof Rats from Organophosphate Poisoning. DESHPANDE, S. S., VIANA,G. B., KAUFFMAN, F. C., RICKETT, D. L., AND ALBUQUERQUE, E.X. (1986). Fundam. Appl. Toxicol. 6, 566-577. The effectivenessof physo stigmine and atropine pretreatment against the lethaleffects of sarin was studied in rats given lethal subcutaneousinjections (130 µg/kg) of the organophospate. Pretreatmentof these animals with physostigmine 30 min prior to injectionof sarin reduced mortality to 28% and when the drug coadministeredwith atropine only 4% of the animals died. The latter treatmentalso reduced significantly the extent and duration of symptomsdue to sarin; however, atropine, pyridostigmine, and neostigmineinjected alone did not protect animals against the lethal effectsof sarin. Physostigmine caused only slight inhibition of cholinesterasein blood and skeletal muscle. Cholinesterase activity in bloodand muscle of rats pretreated with physostigmine before sarinadministration was significantly higher than in tissues fromrats injected with sarin alone. In rats receiving sarin followingpretreatment with physostigmine, twitch potentiation of extensormuscles and maintenance of tension during tetanic stimulationof the nerve recovered to near control levels. Muscle functionrecovered despite significant inhibition of cholinesterase.Effective protection against lethality by physostigmine couldbe related to protection of cerebral cholinesterase since inhibitionof this enzyme by satin was lowered significantly after pretreatmentwith physostigmine. Alternatively, physostigmine may also interactwith the nicotinic acetylcholine receptor ion-channel complexdirectly.