Nicotinic cholinoceptors

Some cholinesterase inhibitors also inhibit butyrylcholinesterase (pseudocholinesterase). Flowever, inhibition of butyrylcholinesterase plays little role in the action of indirect-acting cholinomimetic drugs because this enzyme is not important in the physiologic termination of synaptic acetylcholine action. Some quaternary cholinesterase inhibitors also have a modest direct action as well, eg, neostigmine, which activates neuromuscular nicotinic cholinoceptors directly in addition to blocking cholinesterase. 

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). 

Neuromuscular transmission (B) of motor nerve impulses to the striated muscle fiber takes place at the motor end plate. The nerve impulse liberates acetylcholine (ACh) from the axon terminal. ACh binds to nicotinic cholinoceptors at the motor end plate. This causes depolarization of the postsynaptic membrane, which in turn elicits a propagated action potential (AP) in the surrounding sarcolemma. The AP triggers a release of Ca2+ from its storage organelles, the sarcoplasmic reticulum (SR), within the muscle fiber the rise in Ca2+ concentration induces a contraction (electromechanical coupling). Meanwhile, ACh is hydrolyzed by acetylcholinesterase (p. 104) excitation of the end plate subsides. If no AP follows, Ca2+ is taken up again by the SR and the myofilaments relax. 

DMPP (1,1-dimethyl-4-diphenylpiperazinium iodide) is a NICOTINIC CHOLINOCEPTOR AGONIST that acts as a ganglionic stimulant. It is used as a pharmacological tool. 

Faverin fluvoxamine. fazadinium bromide [ban. inn] is a bisquaternary amine complex heterocyclic compound, which acts as a NICOTINIC cholinoceptor ANTAGONIST, a (competitive) NEUROMUSCULAR BLOCKING AGENT. It can be used as a SKELETAL MUSCLE RELAXANT in anaesthesia, fazarabine [inn, usan] (Ara-Ac NSC 281272) is an analogue of cytarabine, an antimetabolite cytotoxic agent that has been used in ANTICANCER treatment. 

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