Anticholinesterase activity of ß-carboline-1, 3, 5-triazine hybrids

Abstract The ß-carboline-1,3,5-triazine hydrochlorides 8-13 were evaluated in vitro against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The analysed compounds were selective to BuChE, with IC50 values in the range from 1.0-18.8 µM being obtained. The N-{2-[(4,6-dihydrazinyl-1,3,5-triazin-2-yl)amino]ethyl}-1-phenyl-ß-carboline-3-carboxamide (12) was the most potent compound and kinetic studies indicate that it acts as a competitive inhibitor of BuChE. Molecular docking studies show that 12 strongly interacts with the residues of His438 (residue of the catalytic triad) and Trp82 (residue of catalytic anionic site), confirming that this compound competes with the same binding site of the butyrylthiocholine

Comparison of Pseudocholinesterase Activity between Nonpregnant and Term-pregnant Women with the Genotypically Normal Enzyme / 대한마취과학회지

BACKGROUND: Many reports on the change of pseudocholinesterase activity in pregnant women showed that it declines during pregnancy and in the immediate postpartum period. In Korea, there are two papers that show dissident results. However, they didn't prove that the subjects in their studies had genotypically normal enzyme. So, we compared the pseudocholinesterase activities between nonpregnant and term-pregnant women who have the genotypically normal enzyme. METHODS: We measured the dibucaine, fluoride, chloride number as well as the pseudocholinesterase astivity using butyrylthiocholine as substrate by automatic analyser, urea and scoline numbers using benzoylcholine as substrate by manual technique in nonpregnant(n=15) and term-pregnant(n=15) women aging 20 to 40 years old before induction of anesthesia. RESULTS: The dibucaine, fluoride, chloride, urea and scoline numbers(mean+/-SD,%) in female subjects were 86+/-1.2, 50+/-5.2, 5+/-2.4, 47+/-2.8 and 92+/-2.0, respectively. There were two subjects showing low pseudocholinesterase activity(<4.8 U/ml) and the one(3.9 U/ml) was in nonpregnant group, the other(4.5 U/ml) in term-pregnant group. We found that they had genotypically normal enzymes because their inhibition numbers were within normal ranges. Pseudocholinesterase activity(mean+/-SD) in term-pregnant group(7.04+/-1.30) was significantly decreased compared with that in nonpregnant group(9.15+/-2.01)(P<0.01). CONCLUSIONS: We conclude that in subjects with the genotypically normal enzyme, term-pregnant women had significantly lower pseudocholinesterase activity than nonpregnant ones did.

Species variation in the specificity of cholinesterases in human and rat blood samples.

Acetylthiocholine iodide (ATC) as a common substrate in the combined assay of red blood cell cholinesterase (RBC ChE) and butyrylcholinesterase (BuChE) do not provide the accurate individual enzyme activities. Hence, in the present study the two enzyme activities in the same sample were assayed with the help of two different substrate, ATC and butyrylthiocholine iodide (BTC). Specificity of BTC towards BuCHE was found in blood, plasma and serum, while ATC is nonspecifically hydrolysed by both RBC ChE and BuChE. ATC gives significantly higher enzyme activity (P < 0.001) in rat plasma/serum and significantly lower enzyme activity (P < 0.0001; P < 0.001) in human plasma/serum. The possible reasons are discussed for substrate specity in various species in the assay of ChEs.

Influence of age and sex on pseudocholinesterase activity of Korean adults / 대한마취과학회지

Serum pseudocholinesterase activities, using butyrylthiocholine as substrate, measured in 639 employees of Korea Cancer Center Hospital in 1993. Overall mean value of pseudocholinesterase was 9.38+/-2.10 U/ml, 10.6+/-2.10 U/ml in male, and 8.58+/-1.67 U/ml in female, respectively. Male in the first five decades of life had higher pseudocholinesterase activity than female, and after the age of 50 tbere was no intersexual difference. These findings suggest that adults before the age of 50, male has higher pseudocholinesterase activity than female.

Improved colorimetric method for cholinesterase activity.

A modified colorimetric method for the estimation of cholinesterase activity has been worked out using two different substrates, acetylthiocholine iodide for total cholinesterase and a specific substrate, butyrylthiocholine iodide for pseudocholinesterase in the same sample. This is a modification of the method described by Voss and Sachsse (1970) wherein acetylthiocholine iodide was used for both total and pseudo cholinesterase activities. The pseudocholinesterase obtained with acetylthiocholine iodide was significantly higher (P < 0.0001) than that with butyrylthiocholine iodide either in whole blood or serum samples. Acetylthiocholine iodide while reacting with pseudocholinesterase in serum or plasma samples might also be interacting with the small quantities of acetylcholinesterase present. It is therefore suggested that butyrylthiocholine iodide and acetylthiocholine iodide may be used to determine pseudocholinesterase and total cholinesterase activities respectively. The use of two substrates with a few more alterations in the experimental conditions increased the validity of this simple and rapid colorimetric method.

Pralidoxime as an insignificant reactivator in severe anticholinesterase (organophosphate insecticide) poisoning.

In acute severe anticholinesterase poisoning by organophosphate compounds, pralidoxime (P-2-AM, pyridine-2-aldoxime methiodide) used in the recommended doses, intravenously, has not been shown to reactivate the inhibited cholinesterase, as evidenced both clinically and biochemically. In vitro studies using pralidoxime iodide up to ten times the recommended concentrations, produced insignificant reactivation of cholinesterases inhibited by the organophosphate insecticide Bidrin (di-methyl-3-hydroxyl-N, N-dimethyl-crotonamide phosphate). This was even so despite prolonged exposure of the inhibited cholinesterases to the oxime. The value of pralidoxime as a reactivator of phosphorylated cholinesterases is therefore in doubt, and should not be used in preference to large doses of atropine and other supportive treatment in poisoning by organophosphate insecticides.