The effect of ondansetron on pyridostigmine-induced blood acetylcholinesterase inhibition in the guinea pig.
The purpose of this study was to assess the compatibility, in terms of red blood cell acetylcholinesterase (AChE) inhibition, of ondansetron (OND; a 5-hydroxytryptamine subtype-3 receptor antagonist) with the organophosphorus pretreatment compound pyridostigmine (PYR) after simultaneous oral (p.o.) administration to guinea pigs. The time-course of PYR-induced (0.94 mg/kg, p.o.) AChE inhibition was determined in the absence and presence of OND. Ondansetron (10, 20 and 30 mg/kg; p.o.) did not modify AChE inhibition, whereas concurrent administration of PYR with OND (10 or 20 mg/kg; p.o.) produced significantly greater decreases in AChE activity than PYR alone. The decreases in AChE activity for PYR plus OND, 10 and 20 mg/kg, (between 30 -240 min) were 12.3 +/- 2.8% and 16.1 +/- 2.3% (mean +/- SD) respectively relative to PYR alone. The slope for recovery of AChE activity (120 - 240 min) was 0.0914 for PYR alone; recovery rates (slopes) for PYR plus OND, 10 and 20 mg/kg, were 0.0796 and 0.0433 respectively. Additionally, altered PYR-induced AChE activity profiles were ameliorated when PYR and OND (20 mg/kg) were administered 150 min apart. Since the results of this study provided evidence that the oral administration of OND alone did not inhibit AChE, the changes in PYR-induced AChE activity by the simultaneous administration of OND suggest mechanisms other than a direct action on the enzyme. The significance of these findings is that the increased AChE inhibition resulting from simultaneous oral administration of both component could result in undesirable cholinergic toxicities and subsequent perform decrements.
Capacio
B R
BR
Pharmacology Division U.S. Army Medical Research Institute of Chemical Defense Aberdeen Proving Ground, Maryland 21010-5425, USA.
Byers
C E
CE
Anderson
D R
DR
Matthews
R L
RL
Brown
D E
DE
D000110:Acetylcholinesterase / Q000097:blood / Q000187:drug effects* / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D000932:Antiemetics / Q000008:administration & dosage / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D004912:Erythrocytes / Q000201:enzymology; D006168:Guinea Pigs; D008297:Male; D017294:Ondansetron / Q000008:administration & dosage / Q000494:pharmacology*; D011729:Pyridostigmine Bromide / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D000932:Antiemetics; D002800:Cholinesterase Inhibitors; D017294:Ondansetron; D000110:Acetylcholinesterase; D011729:Pyridostigmine Bromide