AChE reversible inhibitor, action

Compared with AChE in animals such as horse and rat, HA is a weaker inhibitor of human serum BuChE. This selectivity for AChE as opposed to BuChE (similar to that of galanthamine) may suggest a better side-effects profile. However, a stronger inhibition of BuChE could be important in the later stage of AD and could offer more protection over amyloid p-peptide (Ap) plaque deposition. In contrast to isoflurophate, the AChE activity did not decrease with the prolongation of incubation with HA in vitro, and the AChE activity returned to 94% of the control after being washed five times, which indicates a reversible inhibitory action. ... 

Scheme 1 Action of AChE on ACh. E, enzyme AX, substrate (ACh) or inhibitor EAX, reversible enzyme complex k, reaction-rate constants.

Phase 2—continued depolarization causes a flaccid paralysis because E-C coupling depends on repolarization and repetitive firing to maintain muscle tension. AChE inhibitors do not reverse this action. 

The mode of action of the carbamate insecticides is similar to that of the organophosphates. As shown in Figure 7.15, the reaction yields a carbamylated AChE, followed by decarbamylation via hydrolysis. Carbamates also attack the CNS system, and the symptoms of intoxication are similar to those with the organophosphates. However, unlike the organophosphates, decarbamylation of acetylcholinesterase is rapid, typically in minutes, and therefore carbamate insecticides are regarded as reversible acetylcholinesterase inhibitors. 

As mentioned above, galantamine has two basic mechanisms of action. It reversibly inhibits cholinesterases, being approximately 50-fold more potent as an AChE inhibitor than a BuChE inhibitor. It also interacts directly with nAChRs, potentiating their activation by subsaturating concentrations of classical agonists (Pereira et al., 2002). 

I Tertiary alkaloid, reversible acetylcholinesterase inhibitor, also potentiates the action of ACh at nicotinic receptors. 

Although both ACh and the AChE inhibitor (physostigmine) can decrease HR by causing activation of M receptors in the heart, this action would not be antagonized or reversed by the ganglion blocker trimethaphan. 

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