caa a22 4500 445853328 CHVBK 20180317145420.0 cr unu---uuuuu 170323e20110301xx s 000 0 eng 10.1007/s00204-010-0571-3 doi (NATIONALLICENCE)springer-10.1007/s00204-010-0571-3 Treatment efficacy in a soman-poisoned guinea pig model: added value of physostigmine? [Elektronische Daten] [Marloes Joosen, August Smit, Herman van Helden] Current treatment of organophosphate poisoning is insufficient, and survivors may suffer from long-lasting adverse effects, such as cognitive deficits and sleep-wake disturbances. In the present study, we aimed at developing a guinea pig model to investigate the benefits of immediate and delayed stand-alone therapy on the development of clinical signs, EEG, heart rate, respiration and AChE activity in blood and brain after soman poisoning. The model allowed the determination of the therapeutic effects at the short-term of obidoxime, atropine and physostigmine. Obidoxime exerted the highest therapeutic efficacy at administration of the lowest dose (3.1mg/kg i.m.), whereas two higher doses (9 and 18mg/kg) were less effective on most parameters. Addition of atropine at 0.03 and 3mg/kg (i.m.) to the treatment did not improve the therapeutic effects of obidoxime alone. Physostigmine (0.8mg/kg im) at 1min after poisoning increased mortality. Two lower doses (0.1 and 0.3mg/kg i.m.) showed improvements on all parameters but respiration. The middle dose was most effective in preventing seizure development and therefore assessed as the most efficacious dose. Combined treatment of obidoxime and physostigmine shortened the duration of seizures, if present, from up to 80min to ~10-15min. In practice, treatment will be employed when toxic signs appear, with the presence of high levels of AChE inhibition in both blood and brain. Administration of physostigmine at that moment showed to be redundant or even harmful. Therefore, treatment of OP poisoning with a carbamate, such as physostigmine, should be carefully re-evaluated. The Author(s), 2010 Soman nationallicence Physostigmine nationallicence Organophosphate nationallicence Seizures nationallicence Obidoxime nationallicence Joosen Marloes TNO Defence, Security and Safety, BU CBRN Protection, Lange Kleiweg 137, 2288 GJ, Rijswijk, The Netherlands aut Smit August Centre for Neurogenomics and Cognitive Research, VU University, Amsterdam, The Netherlands aut van Helden Herman TNO Defence, Security and Safety, BU CBRN Protection, Lange Kleiweg 137, 2288 GJ, Rijswijk, The Netherlands aut Archives of Toxicology Springer-Verlag 85/3(2011-03-01), 227-237 0340-5761 85:3<227 2011 85 204 https://doi.org/10.1007/s00204-010-0571-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-010-0571-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Joosen Marloes TNO Defence, Security and Safety, BU CBRN Protection, Lange Kleiweg 137, 2288 GJ, Rijswijk, The Netherlands aut NATIONALLICENCE 700 1- Smit August Centre for Neurogenomics and Cognitive Research, VU University, Amsterdam, The Netherlands aut NATIONALLICENCE 700 1- van Helden Herman TNO Defence, Security and Safety, BU CBRN Protection, Lange Kleiweg 137, 2288 GJ, Rijswijk, The Netherlands aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85/3(2011-03-01), 227-237 0340-5761 85:3<227 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer