Efficacy comparison of two cholinolytics, scopolamine and azaprophen, when used in conjunction with physostigmine and pyridostigmine for protection against organophosphate exposure

Pretreatment with either pyridostigmine (PYR) or physostigmine (PHY) followed by atropine-oxime therapy is very effective in reducing the lethality of organophosphorus nerve agents. The therapeutic efficacy of scopolamine (SCP) versus azaprophen (AZA), when used in conjunction with PHY and PYR (PHY/PYR) combination pretreatment, was evaluated in guinea pigs challenged with 2 half-lethal doses of soman. Maximum postsoman decrement of rotarod performance was measured. Response surface methodology was employed to describe the relationship between the decrement and the PHY/PYR dosages. Results show that AZA is a more effective pretreatment adjunct at the behavioral deficit-free doses tested, AZA or SCP is as effective with PHY alone as with a PHY/PYR combination. Thus, PYR adds essentially nothing to the carbamate combination against soman-induced behavioral deficit.