Synthesis and Structure-Activity Relationships of Neuromuscular Blocking Agents

Abstract

The first use of neuromuscular blocking agents (muscle relaxants) in clinical practice (1942) revolutionised the practice of anaesthesia and started the modern era of surgery. Since 1942 introduction of tubocurarine (18) neuromuscular blocking agents have been used routinely to provide skeletal muscle relaxation during surgical procedures allowing access to body cavities without hindrance from voluntary or reflex muscle movement. After the introduction of tubocurarine and the depolarizing suxamethonium chloride (4) (1949) several nondepolarizing steroidal and nonsteroidal neuromuscular blocking agents with different onset time and duration of effect were introduced e.g. gallamine triethiodide (1) (1949), methocurine (2) (1949), alcuronium chloride (3) (1963), pancuronium bromide (9) (1968), vecuronium bromide (11) (1982), pipecuronium bromide (10) (1982), atracurium besylate (5) (1982), doxacurium chloride (6) (1991), mivacurium chloride (8) (1992), rocuronium bromide (12) (1994) cisatracurium besylate (7) (1996), and rapacuronium bromide (13) (2000). SZ 1677 (14) a steroid type nondepolarizing neuromuscular blocking agent under development (preclinical phase). This review article deals with a comprehensive survey of the progress in chemical, pharmacological and, in some respects, of clinical studies of neuromuscular blocking agents used in the clinical practice and under development, including the synthesis, structure elucidation, pharmacological actions, structure activity relationships studies of steroidal and nonsteroidal derivatives.

Spinal cord - skeletal muscle cocultures detect muscle-relaxant action of botulinum neurotoxin A

“…From studies on muscle-relaxant agents it is well known that blockade of at least 75% of postsynaptic nicotinic acetylcholine receptors is required to produce signs of muscle relaxation in humans and animals (Jonsson et al, 2006;Tuba et al, 2002). This finding suggests that incomplete cleavage of SNAP-25, e.g., by low concentrations of botulinum toxin A, is detected by Western blot analysis, but may not translate into a decrease in muscle tone.…”

Prolonged paralysis related to mivacurium: A case study

“…[15][16][17][18] During the past few years, NDMRs such as mivacurium, rocuronium, and rapacuronium, have been introduced. 19 Rapacuronium has since been removed from the market because of its association with bronchospasm.…”

3,16-Bisquaternary ammonium steroid derivatives as neuromuscular blocking agents: Synthesis and biological evaluation

“…45 Nowadays, NMBAs are commonly used in surgery as assistant 46 anesthetics to achieve muscle relaxation at the stage of light anes- 47 thesia, such that the severe harm brought by deep anesthesia can 48 be avoided. 49 Structurally, most NMBAs comprise two essential quaternized 50 N atoms connected by various spacers [1][2][3][4][5][6]. The steroid frame-51 work is among the mainstream spacers due to the following advan-52 tages [1][2][3].…”