Neuromuscular junction 16-22 hours

With severe intoxication by all routes, an excess of acetylcholine at the neuromuscular junctions of skeletal muscle causes weakness aggravated by exertion, involuntary twitchings, fasciculations, and, eventually, paralysis. The most serious consequence is paralysis of the respiratory muscles in fatal cases death usually occurs within 24 hours. Effects on the central nervous system include giddiness, confusion, ataxia, slurred speech, Cheyne-Stokes respiration, convulsions, coma, and loss of reflexes. The blood pressure may fall to low levels, and cardiac irregularities including complete heart block may occur. ... 

Actions Physostigmine has a wide range of actions because it stimulates not only muscarinic and nicotinic sites of the autonomic nervous system but also the nicotinic receptors of the neuromuscular junction. Its duration of action is about 2-4 hours. Physostigmine can enter and stimulate the CNS. 

IMS is clearly a separate clinical entity from acute cholinergic crisis and delayed neuropathy. The acute cholinergic crisis usually emerges within a few minutes to a few hours and is due to acetylcholinesterase (AChE) inhibition resulting in acetylcholine accumulation at the synapses in the nervous system and at the neuromuscular junctions. Patients acutely poisoned with OPs exhibit muscle fasciculations. 

After a two-hour ischaemia apphed to one of the rat hind limbs reperfusion injury lesions were confined to the nerve terminals on the presynaptic side of the neuromuscular junction affecting the mitochondria primarily, the synaptic vesicles, the presynaptic membrane, and finally a large number of terminals degenerated (TOmbOl etal. 2000). The Schwann cells were activated, as well as the macrophages. Recovery started 1 day after reperfusion and free synaptic surfaces were found 4 weeks following reperfusion. 

This can be clearly seen by observing the change in the miniature endplate potential (MEPP). The MEPP is a very small potential, observed in the neuromuscular junction, that is due to the natural leakage of acetylcholine from the vesicle. When p-toxin is applied, the MEPP frequently decreases first (5-10 min), then suddenly increases (for several hours). Finally, the frequency decreases until it becomes zero. 

---