Nicotine Neuromuscular blockers

The answer is d. (Hardman, pp 142—M3.) ACh will stimulate both muscarinic and nicotinic receptors. Skeletal muscle contraction is mediated through NM receptors, and ganglionic stimulation is an effect of NN receptors All of the other effects listed in the question occur following muscarinic receptor activation and will be blocked by atropine and scopolamine, both of which are muscarinic receptor antagonists. Skeletal muscle contraction will not be affected by these drugs rather, a neuromuscular blocker (e.g., tubocurarine) is required to antagonize this effect of ACh. 

Acetylcholine antagonists (blockers) that block the nicotine-like effects (neuromuscular blockers and autonomic ganglion blockers) are described elsewhere (see Ch. 18). 

Mechanistically, neuromuscular blockers combine with nicotinic receptors on the postsy-naptic membrane to block competitively acetylcholine (ACh) binding. This prevents conformational changes of, and sodium passage through, the ion channels in the membrane. Once applied to the neuromuscular end-plate, NMBAs desensitize the muscle cells to motor-nerve impulses and ACh. Chemical structures of acetylcholine and representative NMBAs are depicted in Figure 10.1. 

Some of the new fa/s-quaternary ammonium agents produced depolarization of the postjunctional membrane at the neuromuscular junction before causing blockade other compounds, such as tubocurarine, did not produce this depolarization. Thus, the structural features of the remainder of the molecule determined whether the nicotinic antagonist was a depolarizing or a nondepolarizing neuromuscular blocker. 

Nicotinic cholinergic syndrome. Stimulation of nicotinic receptors at autonomic ganglia activates both parasympathetic and sympathetic systems, with unpredictable results. Excessive stimulation frequently causes depolarization blockage. Thus, initial tachycardia may be followed by bradycardia, and muscle fasciculations may be followed by paralysis. (Examples nicotine in addition, the depolarizing neuromuscular blocker succinyl-choline, which acts on nicotinic receptors in skeletal muscle.)... 

Non-depolarising neuromuscular blockers (NMBs) in normal doses act by competitive inhibition of the interaction between acetylcholine and nicotinic receptors. In higher doses, they are thought to block the ion channel as well, which explains the decreased effectiveness of AChE inhibitors in treating non-depolarising neuromuscular blocker toxicity. 

Another possible target for toxins are the receptors for neurotransmitters since such receptors are vital, especially for locomotion. In vertebrates the most strategic receptor is that for acetylcholine, the nicotinic receptor. In view of the breadth of action of the various conotoxins it is perhaps not surprising that alpha-conotoxin binds selectively to the nicotinic receptor. It is entirely possible that similar blockers exist for the receptors which are vital to locomotion in lower species. As mentioned previously, lophotoxin effects vertebrate neuromuscular junctions. It appears to act on the end plate region of skeletal muscle (79,59), to block the nicotinic receptor at a site different from the binding sites for other blockers (81). 

Neuromuscular - mild stimulation to muscle paralysis, respiratory failure (curare), death Tobacco -South American -Strychnos family (curare) Blue green alga (anatonin A) Nicotine - blocks acetylcholine receptors Curare - used as a hunting poison, very potent receptor blocker... 

Like in the neuromuscular junction the neurotransmission can be inhibited either by receptor blockade (non-depolarizing) or by overstimulation (depolarizing) of the receptors. The alkaloid nicotine, in low doses, stimulates ganglia and the adrenaline release from the adrenal medulla. High doses lead to a continuous depolarization of the postsynaptic membrane and thereby to an inactivation of the neurotransmission. All ganglion blockers in clinical use were synthetic amines of the nondepolarizing type trimethaphan, hexamethonium and mecamylamide. 

Ganglion blockers competitively block nicotinic cholinoceptors on postganglionic neurons in both sympathetic and parasympathetic ganglia. In addition, these drugs may directly block the nicotinic acetylcholine channel, in the same fashion as neuromuscular nicotinic blockers (see Figure 27-6). 

Disubstituted piperidines (and piperideines) from ants have insecticidal activity and, as venom constituents, serve the ant in a defensive, repellant function (149). 2,6-Disubstituted piperidines are potent noncompetitive blockers of nicotinic receptor-channels in neuromuscular preparations (162) and in electric eel electroplax (163). Synthetic 241D was a potent noncompetitive blocker of nicotinic receptor-channels in both electric eel electroplax and pheochromocytoma cells (64). 

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