Inhibition of pseudocholinesterase activity protects from cocaine-induced cardiorespiratory toxicity in rats.
We studied the effect of inhibition of pseudocholinesterase by a specific pseudocholinesterase inhibitor, tetraisopropyl pyrophosphoramide (ISO-OMPA) on the cardiorespiratory toxicity of intravenously injected cocaine in rats. Group 1 rats received ISO-OMPA subcutaneously, whereas group 2 rats received saline placebo subcutaneously. Thirty minutes later, rats were anesthetized with 40 mg/kg of sodium pentobarbital intraperitoneally and were then given 10 mg/kg (least toxic dose) cocaine intravenously. Thirty minutes after the first injection of cocaine, about half of the rats that survived from each group were given 12 mg/kg cocaine (low toxic dose) intravenously, and the other half was given 13.5 mg/kg cocaine (high toxic dose) intravenously. Five minutes after each injection, rats were classified as either survivors or fatalities. In group 1 (ISO-OMPA treated), five of 29 (17%) rats that received 10 mg/kg cocaine, two of 11 (19%) that received 12 mg/kg cocaine, and three of 13 (24%) that received 13.5 mg/kg cocaine died of cardiorespiratory toxicity. In group 2 (saline treated), two of 29 (7%) that received 10 mg/kg cocaine, six of 12 (50%) that received 12 mg/kg cocaine, and 10 of 15 (67%) that received 13.5 mg/kg cocaine died of cardiorespiratory toxicity (p less than 0.03). Pseudocholinesterase activity (mean +/- SEM) of groups 1 and 2 were 0.6 +/- 0.2 and 7.3 +/- 0.7 units, respectively (p less than 0.01). Our results show that rats with lower pseudocholinesterase activity had lower fatality rates than rats with higher pseudocholinesterase activity.
Kambam
J R
JR
Department of Anesthesiology, Vanderbilt University Hospital, Nashville, TN 37232-2125.
Naukam
R
R
Berman
M L
ML
D000818:Animals; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003042:Cocaine / Q000633:toxicity*; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration / Q000187:drug effects*; D013770:Tetraisopropylpyrophosphamide / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D013770:Tetraisopropylpyrophosphamide; D002091:Butyrylcholinesterase; D003042:Cocaine