The Emergence of ORG NC 45, 1- [(2β,3α, 5α,16β, 17β)-3, 17-BIS(Acetyloxy)-2-(1-Piperidinyl)-Androstan-16-YL]-1-Methylpiperidinium Bromide, from the Pancuronium Series

Savage, David S.; Sleigh, Thomas; Carlyle, I.

doi:10.1093/bja/52.suppl_1.3s

Cited by 83 publications

(22 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Vecuronium undergoes spontaneous deacetylation to three alcohol metabolites (35). The main metabolite, 3a,37P-diol, is only 2% as potent as the parent drug (Fig.…”

Section: Metabolism and Excretionmentioning

confidence: 99%

Comparison of the Pharmacology of Vecuronium and Atracurium with That of Other Currently Available Muscle Relaxants

Hilgenberg¹

1983

Anesthesia & Analgesia

View full text Add to dashboard Cite

The search for new muscle relaxants is an attempt to improve on the undesirable pharmacologic properties of currently available nondepolarizing muscle relaxants. Ideally, new muscle relaxants would exhibit fewer cardiovascular hemodynamic side effects, have fewer cumulative effects, possess rapid onset of and shorter durations of action, and be less dependent on hepatic and/or renal function for metabolism and excretion. Furthermore, drug metabolites should be pharmacologically inactive. Two new nondepolarizing muscle relaxants, vecuronium (Norcuron) and atracurium (BW 33A), are examples of drugs approaching these ideal muscle-relaxant characteristics. Currently, these drugs are used clinically in Europe and are undergoing clinical trials in this country.

show abstract

“…Vecuronium undergoes spontaneous deacetylation to three alcohol metabolites (35). The main metabolite, 3a,37P-diol, is only 2% as potent as the parent drug (Fig.…”

Section: Metabolism and Excretionmentioning

confidence: 99%

Comparison of the Pharmacology of Vecuronium and Atracurium with That of Other Currently Available Muscle Relaxants

Hilgenberg¹

1983

Anesthesia & Analgesia

View full text Add to dashboard Cite

show abstract

“…Vecuronium (Org NC 45), a recently introduced competitively acting muscle relaxant (Savage et al, 1980;Agoston et al, 1980), is chemically related to pancuronium and it was therefore of interest to test whether any potentiation occurs when these two related drugs are administered in combination. This has been investigated clinically in the present study.…”

Section: Introductionmentioning

confidence: 99%

Dose‐response studies with pancuronium, vecuronium and their combination.

Ferres¹,

Mirakhur²,

Sk³

et al. 1984

Brit J Clinical Pharma

View full text Add to dashboard Cite

1 Pancuronium, vecuronium and a combination of these were administered in an incremental fashion to study any potentiation of effect with the combination of the two relaxants.2 The ED95 (dose producing a 95% block) of the combination was 29 ,ug kg-1 for each component in comparison to 57 ,ug kg-' for vecuronium and 59 ,ug kg-' for pancuronium.3 The dose-response curves for the three groups did not differ from each other and no potentiation was demonstrated.

show abstract

“…This feature favors hepatic uptake of VB. It is also speculated that VB is transported into the hepatic cell by a carrier-mediated process 2 1 • In earlier studies, VB in aqueous solution was found to be hydrolyzed spontaneously within 30 min 25 and VB in plasma was hydrolyzed at a rate of 0.3%10 at neutral pH and room temperature. We examined the decomposition of VB and Org NC 58 (ISTD) in methanol at a concentration of 100 J.Lg·ml-1 • Both VB and Org NC 58 were stable for several months at the concentration when stored at 4°C, but 30% of VB and 80% of Org NC 58 were decomposed at room temperature in ten hours.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and pharmacodynamics of vecuronium bromide

Nomura

1992

J Anesth

View full text Add to dashboard Cite

The pharmacokinetics and pharmacodynamics of vecuronium bromide were studied in patients under general anesthesia of enflurane and nitrous oxide in oxygen. Eighteen patients were randomly divided into two groups which received either 0.05 mg.kg(-1) (low dose group) or 0.20 mg.kg(-1) (high dose group) of vecuronium intravenously. The plasma concentration of vecuronium was determined by high performance liquid chromatography. The neuromuscular blocking effect was assessed by measuring the twitch tension of the adductor pollicis muscle elicited by supramaximal electrical stimulation. Pharmacokinetic analysis was carried out using a two compartment model. The relationship between the T4/T1 and T1/ control T1 ratios differed during onset and spontaneous offset of the blockade; the T4/T1 ratios were significantly higher during onset than during offset, although there were large variations of fade in the train-of-four response in each patient during offset. These results suggest that it is difficult to estimate the T1/control T1 ratio by the T4/T1 ratio during offset. Pharmacokinetic analysis revealed that the high dose group had a shorter elimination half-life than did the low dose group. A shorter elimination half-life at a high dose may be to some extent due to hepatic clearance. The pharmacokinetic parameters bore no fixed relationship to the pharmacodynamics in each patient.

show abstract

The Emergence of ORG NC 45, 1- [(2β,3α, 5α,16β, 17β)-3, 17-BIS(Acetyloxy)-2-(1-Piperidinyl)-Androstan-16-YL]-1-Methylpiperidinium Bromide, from the Pancuronium Series

Abstract: A novel approach is described for obtaining a drug that will be a potent non-depolarizing neuromuscular blocking agent with the potential for a short duration of action and little cumulative effect. This approach led to the discovery of Org NC 45, from the pancuronium series.

Cited by 83 publications

References 0 publications

Comparison of the Pharmacology of Vecuronium and Atracurium with That of Other Currently Available Muscle Relaxants

Comparison of the Pharmacology of Vecuronium and Atracurium with That of Other Currently Available Muscle Relaxants

Dose‐response studies with pancuronium, vecuronium and their combination.

Pharmacokinetics and pharmacodynamics of vecuronium bromide

Contact Info

Product

Resources

About