The Quest for a Short‐Acting Nondepolarizing Neuromuscular Blocking Agent

Abstract

Current developments in the pharmacology of neuromuscular blocking agents indicate that within the next several years, nondepolarizing drugs of short and intermediate duration of action, devoid of significant side effects, may become a reality. The important factors which may permit their development are reviewed.

Haemodynamic Effects of Vecuronium, Pancuronium and Atracurium in Patients With Coronary Artery Disease

“…Such profound anaesthesia in beta-blocked patients coupled with the use of vecuronium probably requires a higher level of vigilance by the anaesthetist than when the heart rate is supported by the administration of pancuronium. This difficulty was foreseen by Savarese and Kitz (1973), who suggested that the relative bradycardia and hypotension caused by most modern anaesthetic techniques may make drugs with a mild vagal blocking effect more acceptable than a drug with a complete lack of cardiovascular effects. It remains to be seen whether the advantages shown by vecuronium plus any decrease in myocardial oxygen consumption which the drug may offer, will be sufficient to overcome the problems of marked bradycardia in certain patients in clinical practice.…”

Development of ultra short‐acting muscle relaxant agents: History, research strategies, and challenges

“…10 The marked increase of NMB potency with the introduction of other bulky terminal groups (e.g., fluorenyl) resulted in the highly potent agent hexafluorenium with mixed depolarizing and non depolarizing mode of action, 11 while introduction of benzyl or m-Br benzyl groups to the terminal N atoms provided same within the first series of diesters of tropine 6 (Table III). The functional role of ''bulky'' groups either at the terminal onium groups or in the linker component of several NMB agents has been discussed 30 with particular reference to A-136, a fairly potent and short acting diester. The terminal onium cations of NMB agents are frequently ''inbedded'' into bicyclic cycloalkane rings.…”

“…102 The conventional methods of detecting blocking action on the M2 receptors are: (a) ligand binding tests utilizing recombinant M2 receptor populations and (b) animal experiments determining the degree of inhibition of bradycardia, produced by vagus nerve stimulation. While some NMB agents have been known to possess primarily M2 receptor blocking property, some of them, particularly those structurally related to atropine, 6,7,30 may also affect other muscarinic receptor subtypes (e.g. those of M1, M3, and M4) and consequently alter their clinical side effects profile.…”

Priming With Alcuronium and Tubocurarine Accelerates the Onset of Neuromuscular Block †

“…The ideal neuromuscular blocking agent should have a rapid onset of action and a non-depolarizing character [1]. In order to accelerate the rate of onset of action, several techniques have been described, including the administration of a large bolus dose several times that required to achieve full neuromuscular block [2], and preliminary priming with a small subparalytic dose of the drug [3].…”