Effects of subacute administration of physostigmine on blood acetylcholinesterase activity, motor performance, and soman intoxication.
Subacute administration of carbamates is under study as pretreatment against soman, a toxic anticholinesterase agent. In this study, the sustained release of physostigmine salicylate (Phy) in rats was achieved via osmotic minipumps; each pump contained 2 ml of Phy solution (0.4, 10, or 50 mg/ml) and delivered 2.5 microliter/hr for 28 days. At the corresponding dosage rates, rat whole blood acetylcholinesterase (AChE) activity was suppressed by approximately 11, 42, and 66%, respectively. These levels of Phy administration caused no decrement in performance on an accelerating rotarod (ARR) when tested between Days 3 and 27 of the 28-day exposure. The highest level of Phy caused a mean weight loss of 11% initially, with recovery by the 17th day. On Day 27 the rats were given 0.08 mg/kg, im, of scopolamine (SCP), 30 min before exposure to soman (58 micrograms/kg; 1 LD50, iv). In combination with SCP, the two highest levels of Phy prevented lethality and a decrement in ARR performance by soman, while the lowest level showed 40% lethality after soman and the survivors exhibited partial recovery to their own presoman control performance by 24 hr. These results suggest that, in a pretreatment mode, 42-66% inhibition of AChE by sustained exposure to Phy, with an acute dose of cholinolytic, would suffice to protect against lethality and motor performance decrement by a toxic level of soman.
Harris
L W
LW
U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5425.
Anderson
D R
DR
Lennox
W J
WJ
Solana
R P
RP
D000110:Acetylcholinesterase / Q000097:blood*; D000818:Animals; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010830:Physostigmine / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D012601:Scopolamine / Q000494:pharmacology; D012999:Soman / Q000506:poisoning*
D012999:Soman; D010830:Physostigmine; D012601:Scopolamine; D000110:Acetylcholinesterase