In vitro competitive inhibition of plasma cholinesterase by cocaine: normal and variant genotypes.

Article Details

Citation

Copy to clipboard

Schwartz HJ, Johnson D

In vitro competitive inhibition of plasma cholinesterase by cocaine: normal and variant genotypes.

J Toxicol Clin Toxicol. 1996;34(1):77-81. doi: 10.3109/15563659609020237.

PubMed ID

8632517 [ View in PubMed

]

Abstract

OBJECTIVE: To determine the inhibitory constant, Ki, of cocaine for a number of the different genetic variants of human plasma cholinesterase. DESIGN: In vitro analysis of plasma cholinesterase activity in the presence of cocaine as a competitive inhibitor. METHODS: Six normal (UU) control sera and seven sera with the following plasma cholinesterase genotypes were assayed: AA, UA, AS, UF, US, AF and SS. Plasma cholinesterase activity was determined in the samples by colorimetric measurement of propionylthiocholine metabolism over a range of concentrations. Competitive activities were then determined in the presence of varying concentrations of cocaine. Double reciprocal plots (1/v vs 1/S) were used to calculate Km and Vmax for propionylthiocholine, and Ki for cocaine for each genotype. RESULTS: The variant forms of the plasma cholinesterase had high cocaine Ki values--all were approximately ten times greater than the Ki for normal plasma cholinesterase. CONCLUSIONS: Since the inhibitory constant is an indirect measure of an enzyme's affinity for a competing substrate, a high Ki for cocaine at recreational or therapeutic concentrations would translate into a longer in vivo half-life. Our results support the growing evidence that low plasma cholinesterase activity predisposes to cocaine toxicity.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Cocaine	Cholinesterase	Protein	Humans	No	Substrate	Details