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Biomedical subjects

J B Stenlake

Publications and source records attributed to J B Stenlake.

At least 19 recordsLinked to original sources
PubMed1997

Neuromuscular blockade: offset anomalies. Are they simply potency-related receptor bonding effects?

Rapid making and breaking of bonds between quaternary ammonium compounds and cholinergic receptors is typical of ion-pair bonding, which is weak, and ion-pair reactions, which are extremely fast. These properties explain the observed rapid association and dissociation of turbocurarine at receptors. The time course receptor offset is determined by two factors, buffered diffusion due to repetitive bonding, and a potency-related offset-retarding effect. The strength of the latter is a function of chemical structure, which determines the microscopic molecular rate of drug-receptor association and dissociation. Together, buffered diffusion and the potency-related offset-retarding effect provide a complete rational physico-chemical explanation for the marked, yet variable, differences between onset and offset times of non-depolarizing neuromuscular blocking agents. The influence of a potency-related offset-retarding effect together with differing structural requirements for neuromuscular blocking potency and plasma carboxyesterase hydrolysis, suggests that a high potency ultrashort duration block is unlikely to be achieved in a non-depolarizing compound metabolized by plasma esterases alone.

Animals↗
PubMed1996

Approaches to short-acting neuromuscular blocking agents: nonsymmetrical bis-tetrahydroisoquinolinium mono- and diesters.

Nonsymmetrical bisquaternary mono- and diesters combining the potency-enhancing properties of the (1R)-laudanosinium group with a second unhindered quaternary ammonium moiety have been studied as a means of promoting short action with high-potency neuromuscular block. Atracurium-related nonsymmetrical diesters showed high potency, freedom from vagal blockade at neuromuscular blocking doses, and short action. Nonsymmetrical monoesters were short acting but showed varying degrees of vagal block.

Animals↗
PubMed1983

Atracurium: conception and inception.

The rationale underlying the design of atracurium, a bis-quaternary ammonium neuromuscular blocking agent which incorporates the Hofmann elimination as a novel biodegradation pathway, is described. Destruction in vivo, of the bis-quaternary structure essential for neuromuscular blocking activity, by the combination of Hofmann elimination and a parallel ester hydrolysis leads to innocuous breakdown products that are without neuromuscular or cardiovascular effects and to a time-course of action which is unaffected by the level of plasma esterase activity, renal or hepatic function.

Animals↗
PubMed1981

A preliminary assessment of atracurium, a new competitive neuromuscular blocking agent.

Atracurium besylate, 2,2'-(3,11-dioxo-4,10-dioxatridecylene)-bis-[6,7-dimethoxy-1-(3,4-dimethoxybenzyl)-2-methyl 1,2,3,4-tetrahydroisoquinolinium] dibenzenesulphonate is a potent non-depolarising (competitive) neuromuscular blocking agent in the cat, monkey, dog and anaesthetized man. In man, it caused complete paralysis of the tetanic response of the adductor pollicis muscles at doses of 0.2 mg/kg. Blockade was of medium duration with rapid spontaneous recovery, and was readily reversed by neostigmine. The electrocardiogram, heart rate, arterial blood pressure and central venous pressure were virtually unchanged following doses of 0.2-0.4 mg/kg. Intubation was readily accomplished in 1.5-2 min after administration of 0.25-0.3 mg/kg.

Animals↗
PubMed1977

Identification of 3-methyl-2-thiohydantoin, a metabolite of carbimazole, in man.

1. Classical and high-pressure liquid chromatographic separations were devised for the separation and isolation of the metabolite 3-methyl-2-thiohydantoin from the urine of patients receiving carbimazole orally. 2. 3-methyl-2-thiohydantoin was identified by comparing its absorption and mass spectral properties with authentic material. 3. 3-methyl-2-thiohydantoin was also detected in the plasma of patients receiving methimazole intravenously.

Carbimazole↗