Kinetics of local anesthetic esters and the effects of adjuvant drugs on 2-chloroprocaine hydrolysis.

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Raj PP, Ohlweiler D, Hitt BA, Denson DD

Kinetics of local anesthetic esters and the effects of adjuvant drugs on 2-chloroprocaine hydrolysis.

Anesthesiology. 1980 Oct;53(4):307-14.

PubMed ID

7425357 [ View in PubMed

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Abstract

A rapid, reliable method for the determination of 2-chloroprocaine in serum was developed. The method, using double-beam ultraviolet spectroscopy, provides rapid, accurate analysis of 2-chloroprocaine in the range of 5.5 to 111 microM (1.5--30 microgram/ml), as documented by comparison with the accepted gas chromatographic procedure. The contribution of 4-amino-2-chlorobenzoic acid, the principal metabolite of 2-chloroprocaine, to the total absorbance at 300 nm was examined and found to be negligible. Using the ultraviolet spectrophotometric method, values of the Michaelis-Menton constant (Km) and maximal reaction velocity (Vmax) for hydrolysis of procaine and 2-chloroprocaine by homozygous typical, heterozygous, and homozygous atypical plasma cholinesterase were determined. The Kms for the three genotypes were 5.0, 6.2, and 14.7 microM, respectively, for procaine, and 8.2, 17, and 103 microM, respectively for 2-chloroprocaine. The Vmaxs for the three genotyps were similar for all esters. Vmax for procaine was 18.6 +/- 0.9 nmol/min/ml serum, while Vmax for 2-chloroprocaine was 98.4 +/- 2.1 nmol/min/ml serum. At high concentrations, 2-chloroprocaine acts as an inhibitor of its hydrolysis. The inhibitory effects of lidocaine, bupivacaine, neostigmine, and succinyldicholine on 2-chloroprocaine hydrolysis for homozygous typical and atypical variants, respectively, were studied. Competitive inhibition was demonstrated for all four drugs. However, at clinically significant concentrations, only neostigmine and bupivacaine produced high degrees of inhibition. The competitive inhibition constants (K1) for the typical and atypical variants, respectively, were 3.3 +/- 0.3 microM and 15.1 +/- 4.8 microM for neostigmine, and 4.2 +/- 0.3 microM and 36.9 +/- 9.8 microM for bupivacaine.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Chloroprocaine	Cholinesterase	Protein	Humans	Unknown	Substrate	Details