Subchronic physostigmine pretreatment in guinea pigs: effective against soman and without side effects.
The behavioral and neurophysiological effects of the subchronically administered cholinesterase-inhibitor physostigmine (PHY) (0.025 mg/kg/h) either with or without the muscarinergic antagonist scopolamine (SCO) (0.018 mg/kg/h) were determined in guinea pigs. In contrast to a single injection of PHY, subchronic application by osmotic minipumps of PHY, even without SCO, caused no behavioral or neurophysiological side effects. Also, the efficacy of such a pretreatment in counteracting soman-induced lethality and apparent symptoms of intoxication were determined. After subchronically administered PHY or PHY + SCO, the treated animals were protected against a 3 x LD50 dose of soman.
Philippens
I H
IH
TNO Prins Maurits Lab, Research Group Pharmacology, Rijswijk ZH, The Netherlands.
Busker
R W
RW
Wolthuis
O L
OL
Olivier
B
B
Bruijnzeel
P L
PL
Melchers
B P
BP
D000110:Acetylcholinesterase / Q000097:blood; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000494:pharmacology* / Q000633:toxicity*; D004569:Electroencephalography / Q000187:drug effects; D004594:Electrophysiology; D005074:Evoked Potentials, Visual / Q000187:drug effects; D006168:Guinea Pigs; D008297:Male; D018727:Muscarinic Antagonists / Q000097:blood; D010830:Physostigmine / Q000009:adverse effects / Q000494:pharmacology*; D011950:Receptors, Cholinergic / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D013216:Reflex, Startle / Q000187:drug effects; D012601:Scopolamine / Q000097:blood; D012999:Soman / Q000037:antagonists & inhibitors* / Q000633:toxicity*
D002800:Cholinesterase Inhibitors; D018727:Muscarinic Antagonists; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D012999:Soman; D010830:Physostigmine; D012601:Scopolamine; D000110:Acetylcholinesterase