Side effects of physostigmine as a pretreatment in guinea pigs.
To prevent incapacitation following nerve agent intoxications, it is proposed to replace pyridostigmine by the centrally active carbamate physostigmine (PHY). Behavioral and neurophysiological effects of PHY were determined and whether these effects would be counteracted by scopolamine. In addition, we compared them with the effects of another reversible cholinesterase (ChE) inhibitor ethyl-p-nitrophenylphosphoramidate (PNF) At similar levels of blood AChE inhibition, PHY caused a larger shuttlebox performance decrement than PNF, which was antagonized by scopolamine (0.1 mg/kg). SCO enhanced the PHY-induced increase of the auditory startle response, whereas PNF, with or without scopolamine, had no effect. In the EEG, PHY led to a power increase at the theta 2-alpha 1 band, also found after PNF, and at the theta 1 band. SCO antagonized all EEG effects, but not the effects of PHY on visual evoked responses, in contrast to those of PNF. Based on the different effects of both inhibitors, it is suggested that at relevant doses several PHY-induced phenomena occur that are unrelated to AChE inhibition.
Philippens
I H
IH
TNO Prins Maurits Laboratorium (TNO-PML), Researche group Pharmacology, Rijswijk, The Netherlands.
Wolthuis
O L
OL
Busker
R W
RW
Langenberg
J P
JP
Melchers
B P
BP
D000110:Acetylcholinesterase / Q000097:blood; D000161:Acoustic Stimulation; D000818:Animals; D019540:Area Under Curve; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D004569:Electroencephalography / Q000187:drug effects; D005074:Evoked Potentials, Visual / Q000187:drug effects; D006168:Guinea Pigs; D008297:Male; D009596:Nitrophenols / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010830:Physostigmine / Q000493:pharmacokinetics / Q000494:pharmacology*; D013216:Reflex, Startle / Q000187:drug effects
D002800:Cholinesterase Inhibitors; D009596:Nitrophenols; D009943:Organophosphorus Compounds; C082483:O-ethyl O-4-nitrophenyl phosphoramidate; D010830:Physostigmine; D000110:Acetylcholinesterase