Nicotinic receptors organophosphate inhibition

Diazinon, an anticholinesterase organophosphate, inhibits acetylcholinesterase in the central and peripheral nervous system. Inhibition of acetylcholinesterase results in accumulation of acetylcholine at muscarinic and nicotinic receptors leading to peripheral and central nervous system effects. These effects... 

Nicotine binds to a type of receptor, now called a nicotinic receptor, and causes the same effects as a release of the neurotransmitter acetylcholine at nerve endings. In this it is similar to organophosphates, which lead to excess acetylcholine at nerve endings (see pp. loo-ioi). Nicotine first excites and then inhibits the central nervous system it first stimulates and then paralyses nerves. It reacts with receptors in muscle and nerves, and is able to enter the brain from the bloodstream and interact with nicotinic receptors. At first there is a stimulation, with the smoker experiencing alertness and decreased irritability, aggression, and anxiety. With higher doses there is depression of the brain as a result of saturation of the receptors. 

Symptoms (a) are due to the excess acetylcholine at muscarinic receptors. Symptoms (b) are due to excess acetylcholine at nicotinic receptors. Symptoms (c) are due to the accumulation of acetylcholine in the central nervous system. Acetylcholine accumulates because the organophosphates inhibit the enzyme acetylcholinesterase which normally removes the neurotransmitter substance. 

Another important example is the nicotinic acetylcholine receptor, which is activated by the agonist nicotine causing muscular fibrillation and paralysis. Indirect effects can also occur. For example, organophosphates and other acetylcholinesterase inhibitors increase the amount of acetylcholine and thereby overstimulate the receptor, leading to effects in a number of sites (see chap. 7). Alternatively, botulinum toxin inhibits the release of acetylcholine and causes muscle paralysis because muscular contraction does not take place (see chap. 7). 

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