Drugs acting at the neuromuscular junction

Neuromu.scular transmission can be increased by antichulineslerase drugs (bottom left), which inhibit acetylcholine.sterase and slow down the hydrolysis of acetylcholine in the synaptic cleft (see also Chapters). Heostitmuw and m idmtiyifm e ate used in (lie ireaiment of niyasihenia 

Some agents (top left) act pre.synapiically and block neuromuscular transmission by preventing the release of acetylcholine. 

Acetylcholine is synthesized in motomeurone terminals from choline and aeety coenzynie-A by the enzyme choline acetylininsferase. The choline is taken up into the nerve endings from the extracellular fluid by a special choline carrier located in thelorininai membrane. 

This can be activated by nicotine and for this reason is called a nicotinic receplor. The receptor-channel complex is pentameric and is constructed from four different protein subunits (aaPyE in the adult) that span the membrane and are arranged to form a central pore (channel) through which cations (mainly Na+) flow. Acetylcholine molecules bind to the two a-subunit.s inducing a confoimational change that opens tlic channel for about I millisecond. 

Gallatnine does not block ganglia or release histamine but causes undesirable tachycardia by blocking the Mi-muscarinic receptors, the subtype of acetylcholine receptor that predominates in the heart (Chapter 7). It is rarely used, 

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