Bis- and Mixed-Tetrahydroisoquinolinium Chlorofumarates:  New Ultra-Short-Acting Nondepolarizing Neuromuscular Blockers

Abstract

Page 207. Under Neuromuscular Pharmacology, sentence 1, line 3, "or" should be replaced with "and": Rhesus monkeys (adult males, 8-15 kg) were anesthetized with ketamine (5 mg/kg, im) and sodium pentobarbital (2-5 mg/kg, iv).

A new short‐acting non‐depolarizing muscle relaxant (SZ1677) without cardiovascular side‐effects

“…The distal tendons of the anterior tibial muscles were attached to FT03 transducers. The nerves were stimulated and the indirectly elicited Ps of the anterior tibial muscles were continuously recorded as described above (5).…”

Goodbye Suxamethonium!

“…Of the asymmetric fumarate tetrahydroisoquinolinium derivatives, GW280430A [29] and its reformulated product, and the new halogenated and un-halogenated products AV002 and congeners, are promising and still being pursued. Some are short-acting; some are intermediate.…”

Structure, conformation, and action of neuromuscular blocking drugs †

“…Of timely interest are a new series of asymmetrical diester isoquinolinium compounds 10 and a series of new bis- Fig 6 Atracurium, mivacurium and doxacurium have 4, 5, and 6 methoxy groups, respectively, on each of their onium heads and their NMB potency increases in the same order. The connecting chain of atracurium has two reversed esters.…”

“…Even without enzymatic catalysis, short-acting NMB agents, especially the ultra-short ones, may break down spontaneously. The new asymmetrical isoquinolinium 10 and bistropinium diester compounds (personal information) most likely break down spontaneously in vivo. These compounds have unusual destabilizing molecular structures, such as molecular asymmetry (Fig.…”

“…77 The new asymmetric isoquinolinium compounds appear unusually fast for the potency. 10 The inversed potency±onset relationship is a disappointment. Potency of action is often determined by speci®city of receptor binding.…”