Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the isolation, on a 0.1- to 2-mg scale, of the four stereoisomers of the nerve agent pinacolyl methylphosphonofluoridate (soman), assigned as C(+)P(+), C(+)P(-), C(-)P(+), and C(-)P(-), with more than 99% optical purity. This result was realized by means of (i) complete optical resolution of pinacolyl alcohol, (ii) synthesis of C(+)- and C(-)-soman from the (+)- and (-)-enantiomers of the alcohol, (iii) optimalization of conditions for sterospecific inhibition of alpha-chymotrypsin with the P(-)-isomers of C(+)- and C(-)-soman, followed by isolation of the C(+)P(+)- and C(-)P(+)-isomers, (iv) isolation of the C(+)P(-)- and C(-)P(-)- isomers after incubation in rabbit plasma of C(+)- and C(-)-soman, respectively, which hydrolyzes sterospecifically the P(+)-isomers. Solutions (0.2 mM) of the steroisomers in organic solvents are optically stable for at least a month at -20 degrees C. The bimolecular rate constants for inhibition of electric eel acetylcholinesterase (AChE) at pH 7.7, 25 degrees C, are at least 3.6 X 10(4) larger for the P(-)- than for the P(+)-isomers. AChE from electric eel as well as from mouse erythrocytes inhibited with C(+)P(-)-soman is much more effectively reactivated with the oximes HI-6, HGG-42, and obidoxime than these enzymes inhibited with C(-)P(-)-soman. Similarly, the neuromuscular transmission ( NMT ) in mouse diaphragm strips poisoned with C(+)-soman is more easily restored with HI-6 than NMT of such muscle preparations poisoned with C(-)-soman. The LD50 values (mice, sc) are in accordance with the P(-)/P(+)-ratio of inhibition rates of AChE, i.e. 99, 38, greater than 5000, greater than 2000, 214, 133, and 156 micrograms/kg for C(+)P(-)-, C(-)P(-)-, C(+)P(+)-, C(-)P(+), C(+)-, C(-)-soman, and "soman," respectively. We suggest that mice challenged with a lethal dose of soman (sc) are killed primarily by the C(-)P(-)-isomer.
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PMID:Isolation, in vitro activity, and acute toxicity in mice of the four stereoisomers of soman. 632 47

Children with cerebral palsy may be resistant to paralysis induced by nondepolarizing neuromuscular blocking drugs. Potency of a bolus of succinylcholine in children with cerebral palsy has not been studied previously. Therefore, we measured the response of the adductor pollicis to succinylcholine in children with cerebral palsy anesthetized with propofol and nitrous oxide. Forty children between the ages of 2 and 10.2 yr with spastic quadriplegic cerebral palsy were randomly assigned to receive 100, 175, 250, or 375 micrograms/kg of succinylcholine during anesthesia with propofol and nitrous oxide. The ulnar nerve was stimulated with a train-of-four supramaximal stimulus every 10 s and the compound electromyogram of the adductor pollicis recorded by a Datex NMT monitor. Plasma cholinesterase activity was measured in all patients with three different substrates (propionylthiocholine, benzoylcholine, and succinylcholine). Dibucaine number was also determined using inhibition of benzoylcholine degradation. ED50 of succinylcholine was 146.8 micrograms/kg with 95% confidence intervals of 111.4-193.7 micrograms/kg. ED95 of succinylcholine was 360.5 micrograms with 95% confidence intervals of 273.3-475.5 micrograms/kg. We conclude that children with cerebral palsy are slightly sensitive to succinylcholine, but probably not sufficiently to be clinically important.
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PMID:Dose response of succinylcholine at the adductor pollicis of children with cerebral palsy during propofol and nitrous oxide anesthesia. 776 64