The Neuromuscular Junction—Basic Receptor Pharmacology

Abstract

Shortly after the introduction of neuromuscular (NM) relaxants to clinical practice, it became apparent that certain pathological states were associated with both hyper- and hyposensitivity to the NM effects of depolarizing or agonist-type, and antagonist or nondepolarizing muscle relaxants (NDMR).1 (Depolarizing relaxants such as succinyicholine, SCh and decamethonium should be considered AChR agonists since their pharmacological actions are like acetylcholine (ACh) in that, at least initially, they stimulate AChRs. NDMRs such as dTC are competitive antagonists of the AChRs because they competitively inhibit the effects of ACh). Reports of cardiac arrest, following succinyicholine were also reported to occur in certain patients.2 The availability of quantitative assays for drug concentrations and receptors, together with electrophysiologic and immunologic techniques, have enabled investigators to correlate these alterations in sensitivity of muscle relaxants to pharmacokinetic and pharmacodynamic changes. My lecture will specifically focus on the qualitative and quantitative changes in the nicotinic acetylcholine receptors (AChRs) at the muscle membrane and its relationship to NM relaxant sensitivity. Pathological states, including iatrogenic factors, and the molecular mechanisms, which may play a role in these AChR changes, will be also discussed.