TY - JOUR
T1 - Optimal pre-treatment for acute exposure to the organophosphate dicrotophos
AU - Lorke, Dietrich E.
AU - Nurulain, Syed M.
AU - Hasan, Mohamed Y.
AU - Kuča, Kamil
AU - Petroianu, Georg A.
N1 - Publisher Copyright:
© 2017 Bentham Science Publishers.
PY - 2017
Y1 - 2017
N2 - Background: Reversible cholinesterase inhibitors, when given prophylactically before exposure to organophosphates, are able to decrease organophosphate-induced mortality. However, the efficacy of pyridostigmine, the only pre-treatment substance approved by the US Federal Drug Administration, is unsatisfactory. Methods: In search of a better prophylactic compound, we determined in vivo the protection conferred by five cholinesterase inhibitors (ranitidine, physostigmine, tacrine, K-27 and pyridostigmine), which were administered in equitoxic dosage (1/4 of LD01) 30 minutes before exposure to the organophosphate dicrotophos. Efficacy was measured in rats by Cox analysis calculating the relative risk of death (RR), RR being 1 for the reference group which received dicrotophos and no prophylaxis. Results: K-27 (RR=0.06), physostigmine (RR=0.15), pyridostigmine (RR=0.22) and tacrine (RR=0.28) significantly (p ≤ 0.05) reduced dicrotophos-induced mortality in comparison to the reference group (dicrotophos without pre-treatment), whereas ranitidine (RR=0.86) had no significant influence. The experimental oxime K-27, when given before dicrotophos exposure, conferred the best in vivo protection. This was significantly (p ≤ 0.05) more efficacious than pre-treatment with any other tested compound. The differences in efficacy between the second best compound, physostigmine, and the less efficacious substances (tacrine and pyridostigmine) were also statistically significant. Conclusion: These data indicate that K-27 can be considered a very efficacious prophylactic agent for organophosphate exposure.
AB - Background: Reversible cholinesterase inhibitors, when given prophylactically before exposure to organophosphates, are able to decrease organophosphate-induced mortality. However, the efficacy of pyridostigmine, the only pre-treatment substance approved by the US Federal Drug Administration, is unsatisfactory. Methods: In search of a better prophylactic compound, we determined in vivo the protection conferred by five cholinesterase inhibitors (ranitidine, physostigmine, tacrine, K-27 and pyridostigmine), which were administered in equitoxic dosage (1/4 of LD01) 30 minutes before exposure to the organophosphate dicrotophos. Efficacy was measured in rats by Cox analysis calculating the relative risk of death (RR), RR being 1 for the reference group which received dicrotophos and no prophylaxis. Results: K-27 (RR=0.06), physostigmine (RR=0.15), pyridostigmine (RR=0.22) and tacrine (RR=0.28) significantly (p ≤ 0.05) reduced dicrotophos-induced mortality in comparison to the reference group (dicrotophos without pre-treatment), whereas ranitidine (RR=0.86) had no significant influence. The experimental oxime K-27, when given before dicrotophos exposure, conferred the best in vivo protection. This was significantly (p ≤ 0.05) more efficacious than pre-treatment with any other tested compound. The differences in efficacy between the second best compound, physostigmine, and the less efficacious substances (tacrine and pyridostigmine) were also statistically significant. Conclusion: These data indicate that K-27 can be considered a very efficacious prophylactic agent for organophosphate exposure.
KW - Carbamates
KW - Cholinesterase
KW - Cox analysis
KW - Dicrotophos
KW - Organophosphate
KW - Prophylaxis
KW - Rat
UR - http://www.scopus.com/inward/record.url?scp=85038429446&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85038429446&partnerID=8YFLogxK
U2 - 10.2174/1381612822666161027154303
DO - 10.2174/1381612822666161027154303
M3 - Article
C2 - 27799040
AN - SCOPUS:85038429446
SN - 1381-6128
VL - 23
SP - 3432
EP - 3439
JO - Current Pharmaceutical Design
JF - Current Pharmaceutical Design
IS - 23
ER -