Procaine is a local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. Procaine binds to and inhibits voltage-gated sodium channels, thereby inhibiting the ionic flux required for the initiation and conduction of impulses. In addition, this agent increases electrical excitation threshold, reduces rate of rise of action potential and slows nerve impulse propagation thereby causing loss of sensation.
1 moreTitle: Prediction of drug sensitivity in individuals with atypical serum cholinesterase based on in vitro biochemical studies Valentino RJ, Lockridge O, Eckerson HW, La Du BN Ref: Biochemical Pharmacology, 30:1643, 1981 : PubMed
Title: Differential inhibition of plasma cholinesterase variants using the dibutyrate analogue of pancuronium bromide Whittaker M, Britten JJ Ref: Hum Hered, 31:242, 1981 : PubMed
A steroid, the dibutyrate analogue of pancuronium bromide (9.8 X 10(-8)M), has been used as differential inhibitor in the study of the plasma cholinesterase variants. Pancuronium dibutyrate numbers have been measured for 190 individuals, and the mean values for six of the known genotypes, E1uE1u, E1uE1f, E1uE1a, E1fE1a, E1aE1a, and E1fE1f, have been calculated. Evidence is presented that a combination of the pancuronium dibutyrate number and the fluoride number give better resolution of the six genotypes than the combination of the pancuronium dibutyrate and the dibucaine number. This new differential inhibitor has real potential for revealing the probable existence of new genotypes.
Title: The activity of various esterase inhibitors towards atypical human serum cholinesterase Kalow W, Davies R0 Ref: Biochemical Pharmacology, 1:183, 1958 : PubMed
1 lessTitle: Genetic variants of human serum cholinesterase influence metabolism of the muscle relaxant succinylcholine. Lockridge O Ref: Pharmacol Ther, 47:35, 1990 : PubMed
People with genetic variants of cholinesterase respond abnormally to succinylcholine, experiencing substantial prolongation of muscle paralysis with apnea rather than the usual 2-6 min. The structure of usual cholinesterase has been determined including the complete amino acid and nucleotide sequence. This has allowed identification of altered amino acids and nucleotides. The variant most frequently found in patients who respond abnormally to succinylcholine is atypical cholinesterase, which occurs in homozygous form in 1 out of 3500 Caucasians. Atypical cholinesterase has a single substitution at nucleotide 209 which changes aspartic acid 70 to glycine. This suggests that Asp 70 is part of the anionic site, and that the absence of this negatively charged amino acid explains the reduced affinity of atypical cholinesterase for positively charged substrates and inhibitors. The clinical consequence of reduced affinity for succinylcholine is that none of the succinylcholine is hydrolyzed in blood and a large overdose reaches the nerve-muscle junction where it causes prolonged muscle paralysis. Silent cholinesterase has a frame shift mutation at glycine 117 which prematurely terminates protein synthesis and yields no active enzyme. The K variant, named in honor of W. Kalow, has threonine in place of alanine 539. The K variant is associated with 33% lower activity. All variants arise from a single locus as there is only one gene for human cholinesterase (EC 3.1.1.8). Comparison of amino acid sequences of esterases and proteases shows that cholinesterase belongs to a new family of serine esterases which is different from the serine proteases.
Title: Prediction of drug sensitivity in individuals with atypical serum cholinesterase based on in vitro biochemical studies Valentino RJ, Lockridge O, Eckerson HW, La Du BN Ref: Biochemical Pharmacology, 30:1643, 1981 : PubMed
Title: Differential inhibition of plasma cholinesterase variants using the dibutyrate analogue of pancuronium bromide Whittaker M, Britten JJ Ref: Hum Hered, 31:242, 1981 : PubMed
A steroid, the dibutyrate analogue of pancuronium bromide (9.8 X 10(-8)M), has been used as differential inhibitor in the study of the plasma cholinesterase variants. Pancuronium dibutyrate numbers have been measured for 190 individuals, and the mean values for six of the known genotypes, E1uE1u, E1uE1f, E1uE1a, E1fE1a, E1aE1a, and E1fE1f, have been calculated. Evidence is presented that a combination of the pancuronium dibutyrate number and the fluoride number give better resolution of the six genotypes than the combination of the pancuronium dibutyrate and the dibucaine number. This new differential inhibitor has real potential for revealing the probable existence of new genotypes.
Title: The activity of various esterase inhibitors towards atypical human serum cholinesterase Kalow W, Davies R0 Ref: Biochemical Pharmacology, 1:183, 1958 : PubMed
human-BCHE
