Cholinesterase deficiency

Giurini JM, Hopkins WE, Redner T, et al. 1986. Succinylcholine sensitivity and plasma cholinesterase deficiency. J Foot Surgery 25 382-385. 

Resistance to suxamethonium. This rare condition is characterised by increased pseudocholinesterase activity and failure of normal doses of suxamethonium to cause muscular relaxation (cf Cholinesterase deficiency, above). 

Smith AR, Hur D, Resano F. Grand mal seizures after 2-chloroprocaine epidural anesthesia in a patient with plasma cholinesterase deficiency. Anesth Analg 1987 66(7) 677-8. 

Schuh, F. T., Serum cholinesterase Effect on the action of suxamethonium following administration to a patient with cholinesterase deficiency. Br. ]. Anaesth. 49, 269-272... 

Scott, E. M., Properties of the trace enzyme in human serum cholinesterase deficiency. Biochem. Biophys. Res. Common. 38, 902-906 (1970). 

For most agents, onset and duration is dose- and age-dependent, With succinyichoiine or mivacurium, effects may be prolonged in patients who have genetic plasma cholinesterase deficiency or organophos-... 

The effect of a standard dose of succinylcholine lasts only about 10 min. It is often given at the start of anesthesia to facilitate intubation of the patient. As expected, choUnesterase inhibitors are unable to counteract the effect of succinylcholine. In the few patients with a genetic deficiency in pseudocholinesterase (= nonspecific cholinesterase), the succinylcholine effect is significantly prolonged. 

Medicinal chemistry has many examples of the development of successful therapeutics based on an exploration of endogenous compounds. The treatment of diabetes mellitus, for example, is based upon the administration of insulin, the hormone that is functionally deficient in this disease. The current treatment of Parkinson s disease is based upon the observation that the symptoms of Parkinson s disease arise from a deficiency of dopamine, an endogenous molecule within the human brain. Since dopamine cannot be given as a drug since it fails to cross the blood-brain barrier and enter the brain, its biosynthetic precursor, L-DOPA, has been successfully developed as an anti-Parkinson s drug. Analogously, the symptoms of Alzheimer s disease arise from a relative deficiency of acetylcholine within the brain. Current therapies for Alzheimer s-type dementia are based upon the administration of cholinesterase... 

The medicinal chemistry of Alzheimers is complicated by the fact that the etiology of this disease is still far from clear. Evidence points to an association with decreased levels of acetyl choline in the brain. Many of the drugs that have been introduced to date for treating this disease thus comprise agents intended to raise the deficient levels of that neurotransmitter by inhibiting the loss of existing acetylcholine due to the action of cholinesterase. A compound based on an indene that, perhaps surprisingly, inhibits that enzyme has been proposed for the treatment of Alzheimer s. Aldol condensation of piperidine aldehyde (4-2) with the indanone (4-1) from cyclization of 3,4-dimethoxycinnamic acid leads to the olefin (4-3). Catalytic reduction removes the double bond to afford donepezil (4-4) [3]. 

Pseudocholinesterase deficiency. The neuromuscular blocking action of suxamethonium is terminated by plasma pseudocholinesterase. True cholinesterase (acetylcholinesterase) hydrolyses acetylcholine released by nerve endings, whereas various tissues and plasma contain other nonspecific, hence pseudo, esterases. Affected individuals form so little plasma pseudocholinesterase that metabolism of suxamethonium is seriously reduced. The deficiency characteristically comes to light when a patient fails to breathe spontaneously after a surgical operation, and assisted ventilation may have to be undertaken for hours. Relatives of an affected individual—for this as for other inherited abnormalities carrying avoidable risk—should be sought out, checked to assess their own risk, and told of the result. The prevalence of pseudocholinesterase deficiency in the UK population is about 1 in 2500. 

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