At the nicotinic receptors in ganglia and at the myoneural junction the accumulation of acetylcholine at first leads to an intensification of cholinergic transmission, but with continued accumulation over time, the nicotinic receptors become desensitized. There follows a failure of nicotinic, cholinergic transmission, despite the continued presence of excess transmitter. This results in flaccid paralysis of skeletal muscle and a fall off of sympathetic autonomic function. Parasympathetic autonomic function, however, remains intensified even though the parasympathetic ganglia may have been desensitized. The cholinesterase inhibitor continues to act downstream from the ganglia at the muscarinic site. Thus, at nicotinic synapses, the effects of cholinesterase inhibitors resemble those of nicotine, whereas at muscarinic synapses their effects resemble those of muscarine. Thus, nicotine poisoning resembles anticholinesterase poisoning, but lacks the signs and symptoms referable to stimulation of muscarinic receptors. At both muscarinic and nicotinic sites the effects of cholinesterase inhibitors are, in fact, mediated through acetylcholine leading to the designation of inhibitors as indirectly acting, cholinergic agonists.
