Scopolamine augments the efficacy of physostigmine against soman poisoning in guinea pigs.
The efficacy of the subchronically administered cholinesterase-inhibitor physostigmine (PHY) (0.025 mg/kg/h) either with or without the muscarinergic receptor antagonist scopolamine (SCO) (0.018 mg/kg/h) in counteracting soman-induced lethality and incapacitation were determined in guinea pigs. This was tested in animals that either received atropine sulphate (AS, 17.4 mg/kg i.m.) or no postintoxication therapy. Behavioral and neurophysiological readout systems were used to measure postintoxication incapacitation. Only the pretreatment with PHY alone did not offer any protection against 2x LD50 soman intoxication. Animals that received the complete treatment (PHY + SCO + AS) did not show any abberations in the performance of learned behavior. The use of AS after soman intoxication resulted in an increase of the startle response, whereas the addition of SCO to the pretreatment led to a more persistent duration of the effect in time. In case one has to rely completely on the pretreatment, the addition of SCO to PHY is life-saving. However, some postintoxication incapacitation is still present. Therefore, the pretreatment regime may perhaps further be improved by the addition of a nicotinic antagonist.
Philippens
I H
IH
TNO Prins Maurits Lab, Research Group Pharmacology, Rijswijk ZH, The Netherlands.
Melchers
B P
BP
Olivier
B
B
Bruijnzeel
P L
PL
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D004357:Drug Synergism; D004569:Electroencephalography / Q000187:drug effects; D006168:Guinea Pigs; D008297:Male; D018727:Muscarinic Antagonists / Q000627:therapeutic use*; D010830:Physostigmine / Q000627:therapeutic use* / Q000633:toxicity; D013216:Reflex, Startle / Q000187:drug effects; D012601:Scopolamine / Q000627:therapeutic use* / Q000633:toxicity; D012999:Soman / Q000506:poisoning*
D002800:Cholinesterase Inhibitors; D018727:Muscarinic Antagonists; D012999:Soman; D010830:Physostigmine; D012601:Scopolamine