Neuromuscular Blocking Agents

Neuromuscular Blocking Agents (Skeletal Muscle Relaxants)

1. Definition, scope & classification

• Skeletal muscle relaxants (SMRs) are drugs that reduce muscle tone or produce paralysis by acting (i) peripherally at the neuromuscular junction (NMJ) or on the muscle fibre, or (ii) centrally in the cerebrospinal axis (KDT 8e Ch.25, p.373; Padmaja 7e Ch.8, p.127).
• Neuromuscular blocking agents (NMBAs) are the peripherally acting, NMJ-blocking subset, used chiefly with general anaesthetics to relax skeletal muscle for surgery and to facilitate endotracheal intubation; they lack CNS activity because they are charged quaternary compounds that do not cross the blood–brain barrier (G&G 14e Ch.13, pp.236–7; Katzung 16e Ch.27, pp.499–500).
• Broad classification of skeletal muscle relaxants (KDT 8e Ch.25, pp.373, 382; Padmaja 7e Ch.8, p.127):
  • A. Peripherally acting (neuromuscular blockers)
  • Non-depolarising (competitive) — natural: d-tubocurarine; steroidal (aminosteroid): pancuronium, vecuronium, rocuronium, pipecuronium; benzylisoquinolinium: atracurium, cisatracurium, mivacurium, doxacurium; mixed-onium chlorofumarate (investigational): gantacurium.
  • Depolarising — succinylcholine (suxamethonium); decamethonium (obsolete).
  • B. Directly acting — dantrolene (also quinine).
  • C. Centrally acting (spasmolytics / antispasmodics) — diazepam (GABA_A), baclofen (GABA_B), tizanidine (α₂-agonist), mephenesin congeners (carisoprodol, chlorzoxazone, methocarbamol, chlormezanone), thiocolchicoside, cyclobenzaprine.
• The two clinically used NMBA classes are depolarising (only succinylcholine in general use) and competitive / non-depolarising (multiple agents) (G&G 14e Ch.13, p.237).
• Historical note — Curare is the generic term for South-American arrow poisons (from Strychnos toxifera, Chondrodendron tomentosum) used to paralyse game; death is by skeletal-muscle paralysis. Claude Bernard (mid-19th c.) localised curare's action to "at or near the neuromuscular junction"; King established the structure of tubocurarine in 1935; Griffith and Johnson reported the first use of curare for surgical muscle relaxation in 1942 (G&G 14e Ch.13, pp.236–7; KDT 8e Ch.25, p.374).