Side effects of therapeutic drugs against organophosphate poisoning.
The possible side effects of therapeutic drugs against organophosphate poisoning were investigated. First, dose-effect curves were obtained with atropine sulphate (AS), P2S, obidoxime, aprophen, N-methylatropine nitrate and HI-6. The first three drugs are currently used in the therapy of organophosphate poisoning, the others are potentially useful candidates. Automated tests measuring open field behavior, motor coordination and shuttlebox performance, as well as neurophysiological techniques such as the quantified EEG (qEEG) and visual evoked responses were used. The sign-free doses of these compounds were determined; it appeared that open field behavior and the qEEG were the most sensitive methods for these drugs. Subsequently, these two methods were used to investigate the effects of the combinations of AS and P2S, AS and obidoxime or AS and HI-6, each compound given in a sign-free dose. Synergistic or additive effects were found with the combination of AS and P2S, which were smaller with the combination of AS and obidoxime and absent with the combination of AS and HI-6. These results indicate that the untimely use (false alarm, panic) of the current drug combinations may cause undesirable side effects.
Wolthuis
O L
OL
Medical Biological Laboratory TNO, Rijswijk, The Netherlands.
Philippens
I H
IH
Vanwersch
R A
RA
D000818:Animals; D001285:Atropine / Q000009:adverse effects; D001286:Atropine Derivatives / Q000009:adverse effects; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000009:adverse effects; D004569:Electroencephalography; D005074:Evoked Potentials, Visual / Q000187:drug effects; D008297:Male; D009043:Motor Activity; D009768:Obidoxime Chloride / Q000009:adverse effects; D062025:Organophosphate Poisoning; D010091:Oximes; D010276:Parasympatholytics / Q000009:adverse effects* / Q000627:therapeutic use; D010666:Phenylpropionates / Q000009:adverse effects; D011726:Pyridinium Compounds / Q000009:adverse effects; D051381:Rats; D011919:Rats, Inbred Strains
D001286:Atropine Derivatives; D010091:Oximes; D010276:Parasympatholytics; D010666:Phenylpropionates; D011726:Pyridinium Compounds; D009768:Obidoxime Chloride; D001285:Atropine; C006649:methylatropine; C022870:asoxime chloride; C006615:aprofen