Acetylcholinesterase inhibitors antagonists

Keywords Neurodegenerative diseases Alzheimer s disease Parkinson s disease Cholinergic hypothesis Muscarinic agonists Muscarinic antagonists Nicotinic agonists Acetylcholine releasers Acetylcholinesterase inhibitors High affinity choline uptake enhancers... 

Despite the drawbacks of the cholinergic hypothesis, this idea has guided most of the researchers involved with AD and enormous resources have been invested in developing compounds that would directly (nicotinic and M, selective muscarinic agonists) or indirectly (acetylcholinesterase inhibitors, M2 selective muscarinic antagonists, acetylcholine releasers, high affinity choline uptake inhibitors) increase the level of cholinergic transmission in the brain. 

Acetylcholine Both anticholinergics (antagonists) that block the cholinergic receptor and acetylcholinesterase inhibitors (potentiate acetylcholine) are in use today and are based on the acetylcholine structure. Because of the efficiency of acetylcholinesterase, it has proved more productive to inhibit the enzyme that hydrolyzes this neurotransmitter rather than develop cholinergic agonists. 

Pyriminil toxicity occurs primarily because it inhibits NADH ubiquinone oxidoreductase activity of complex I in mammalian mitochondria resulting in preferential toxicity to high-energy-demanding cells such as nerves and pancreatic jS-cells. However, pyriminil may also act as a nicotinamide antagonist and interfere with the synthesis of NADH/NADPH, furthering neural and jS-cell toxicity. Inhibition of mitochondrial respiration in nerves causes somatic, autonomic, and central nervous system neuropathies while inhibition in jS-cell causes an immediate, irreversible insulin-dependent diabetes mellitus condition. Pyriminil also acts as a noncompetitive inhibitor of rat acetylcholinesterase. 

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