<P> Depolarizing agents Depolarizing agents produce their block by binding to and activating the ACh receptor, at first causing muscle contraction, then paralysis . They bind to the receptor and cause depolarization by opening channels just like acetylcholine does . This causes repetitive excitation that lasts longer than a normal acetylcholine excitation and is most likely explained by the resistance of depolarizing agents to the enzyme acetylcholinesterase . The constant depolarization and triggering of the receptors keeps the endplate resistant to activation by acetylcholine . Therefore, a normal neuron transmission to muscle cannot cause contraction of the muscle because the endplate is depolarized and thereby the muscle paralysed . </P> <P> Binding to the nicotinic receptor Shorter molecules like acetylcholine need two molecules to activate the receptor, one at each receptive site . Decamethonium congeners, which prefer straight line conformations (their lowest energy state), usually span the two receptive sites with one molecule (binding inter-site). Longer congeners must bend when fitting receptive sites . </P> <P> The greater energy a molecule needs to bend and fit usually results in lower potency . </P> <P> Conformational study on neuromuscular blocking drugs is relatively new and developing . Traditional SAR studies do not specify environmental factors on molecules . Computer - based conformational searches assume that the molecules are in vacuo, which is not the case in vivo . Solvation models take into account the effect of a solvent on the conformation of the molecule . However, no system of solvation can mimic the effect of the complex fluid composition of the body . </P>

Primary clinical uses of neuromuscular blocking agents include which of the following