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British Journal of Anaesthesia Oct 1975The interaction of tubocurarine and suxamethonium in man was studied by the use of tetanic and single twitch contractions of the adductor pollicis muscles. Suxamethonium... (Clinical Trial)
Clinical Trial
The interaction of tubocurarine and suxamethonium in man was studied by the use of tetanic and single twitch contractions of the adductor pollicis muscles. Suxamethonium 0.2 mg/kg was administered at the times when the recovery of the tetanic contraction from neuromuscular blockade produced by tubocurarine 0.2 mg/kg had reached 20% and 50% of the control. At the 20% recovery point, suxamethonium improved both the tetanic and single twitch contractions; at the 50% recovery point, the single twitch response was markedly enhanced but the tetanic contraction was depressed. The findings suggest that the interaction of tubocurarine and suxamethonium is both antagonistic and synergistic. The tetanic contraction is more sensitive to the synergistic action compared with the single twitch contraction. When the interaction of these two agents is being evaluated it is important to consider the doses of the agents, the stage of curarization where the interaction took place and the method of assessing the neuromuscular blockade.
Topics: Adult; Aged; Clinical Trials as Topic; Drug Interactions; Humans; Male; Middle Aged; Muscle Contraction; Skin Temperature; Succinylcholine; Tubocurarine
PubMed: 1106737
DOI: 10.1093/bja/47.10.1061 -
Anesthesiology Oct 1971
Topics: Androstanes; Blood Pressure; Depression, Chemical; Ganglionic Blockers; Histamine Release; Humans; Pharmaceutic Aids; Piperidines; Stimulation, Chemical; Tubocurarine
PubMed: 4107153
DOI: 10.1097/00000542-197110000-00028 -
British Journal of Anaesthesia Aug 1973
Topics: Action Potentials; Adult; Electric Stimulation; Electromyography; Humans; Middle Aged; Muscle Contraction; Succinylcholine; Synaptic Transmission; Tubocurarine; Ulnar Nerve
PubMed: 4356717
DOI: 10.1093/bja/45.8.849 -
Molecular Pharmacology Jan 2009The muscle-type nicotinic acetylcholine receptor has two nonidentical binding sites for ligands. The selectivity of acetylcholine and the competitive antagonists...
The muscle-type nicotinic acetylcholine receptor has two nonidentical binding sites for ligands. The selectivity of acetylcholine and the competitive antagonists (+)-tubocurarine and metocurine for adult mouse receptors is known. Here, we examine the site selectivity for four other competitive antagonists: cisatracurium, pancuronium, vecuronium, and rocuronium. We rapidly applied acetylcholine to outside-out patches from transfected BOSC23 cells and measured macroscopic currents. We have reported the IC(50) of the antagonists individually in prior publications. Here, we determined inhibition by pairs of competitive antagonists. At least one antagonist was present at a concentration producing > or =67% receptor inhibition. Metocurine shifted the apparent IC(50) of (+)-tubocurarine in quantitative agreement with complete competitive antagonism. The same was observed for pancuronium competing with vecuronium. However, pancuronium and vecuronium each shifted the apparent IC(50) of (+)-tubocurarine less than expected for complete competition but more than expected for independent binding. The situation was similar for cisatracurium and (+)-tubocurarine or metocurine. Cisatracurium did not shift the apparent IC(50) of pancuronium or vecuronium, indicating independent binding of these two pairs. The data were fit to a two-site, two-antagonist model to determine the antagonist binding constants for each site, L(alphaepsilon) and L(alphadelta). We found L(alphaepsilon)/L(alphadelta) = 0.22 (range, 0.14-0.34), 20 (9-29), 21 (4-36), and 1.5 (0.3-2.9) for cisatracurium, pancuronium, vecuronium, and rocuronium, respectively. The wide range of L(alphaepsilon)/L(alphadelta) for some antagonists may reflect experimental uncertainties in the low affinity site, relatively poor selectivity (rocuronium), or possibly that the binding of an antagonist at one site affects the affinity of the second site.
Topics: Acetylcholine; Androstanols; Animals; Atracurium; Binding Sites; Binding, Competitive; Cell Line; Clone Cells; Dose-Response Relationship, Drug; Drug Synergism; Humans; Inhibitory Concentration 50; Kidney; Mice; Muscle, Skeletal; Neuromuscular Blocking Agents; Nicotinic Antagonists; Pancuronium; Patch-Clamp Techniques; Receptors, Nicotinic; Rocuronium; Transfection; Tubocurarine; Vecuronium Bromide
PubMed: 18842832
DOI: 10.1124/mol.108.051060 -
British Journal of Anaesthesia Jun 1984The effects of small doses of tubocurarine and pancuronium on peak tetanic tension and tetanic maintenance were compared. Forty patients undergoing elective orthopaedic... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
The effects of small doses of tubocurarine and pancuronium on peak tetanic tension and tetanic maintenance were compared. Forty patients undergoing elective orthopaedic procedures under general anaesthesia were studied. Changes in neuromuscular transmission were measured by recording the isometric contraction of the adductor pollicis muscle evoked by supramaximal stimulation of the ulnar nerve at the wrist. Small doses of pancuronium affected predominantly the peak tetanic tension, while small doses of tubocurarine affected mainly tetanic maintenance. Thus, different degrees of depression of peak tetanic tension and tetanic maintenance were observed with tubocurarine and pancuronium. This clinical study supports Bowman's hypothesis, based upon laboratory findings in the cat, that prejunctional and postjunctional effects of neuromuscular blocking agents depend on their affinity for cholinoceptors at different sites.
Topics: Adult; Anesthesia, General; Humans; Muscle Contraction; Neuromuscular Junction; Pancuronium; Synaptic Transmission; Tubocurarine
PubMed: 6326788
DOI: 10.1093/bja/56.6.607 -
Anaesthesia 1978The cardiovascular effects of tubocurarine in patients anaesthetised with thiopentone or ketamine have been compared, using volume-pulse finger plethysmography,...
The cardiovascular effects of tubocurarine in patients anaesthetised with thiopentone or ketamine have been compared, using volume-pulse finger plethysmography, electrocardiography, sphygmomanometry and impedance cardiography for the clinical assessments. Tubocurarine potentiates the arterial hypotensive effect of thiopentone and reverses the hypertensive action of ketamine. It also prevents the dysrhythmic (adrenergic) reaction of the heart to orotracheal intubation and has less effect on the positive chronotropic and inotropic reactions thereto. Hypotensive doses of tubocurarine in patients anaesthetised with thiopentone do not prevent reflex constriction of the finger blood vessels in response to surgical stimuli (orotracheal intubation) which means that the drug is not a sympathetic ganglion blocker in man. It is concluded that tubocurarine is a myocardial depressant which acts, like verapamil, as a calcium ion antagonist.
Topics: Adult; Anesthesia, Intravenous; Blood Pressure; Calcium; Cardiovascular System; Electrocardiography; Female; Humans; Intubation, Intratracheal; Ketamine; Male; Plethysmography; Pulse; Thiopental; Tubocurarine
PubMed: 686328
DOI: 10.1111/j.1365-2044.1978.tb08417.x -
British Journal of Anaesthesia May 1985The onset characteristics of pancuronium, tubocurarine and a mixture of these two neuromuscular blocking drugs were studied during the induction of neuromuscular... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
The onset characteristics of pancuronium, tubocurarine and a mixture of these two neuromuscular blocking drugs were studied during the induction of neuromuscular blockade, using a train-of-four pattern of stimulation. Four characteristics of onset were defined: train-of-four fade = a reduction in the height of the fourth twitch greater than a reduction in the height of the first twitch; latent onset time = time from injection of neuromuscular blocker to a greater than 5% reduction in the first twitch in the train-of-four; total onset time = time to 90% reduction in twitch height; manifest onset time = time from 5% to 90% reduction in twitch height. Tubocurarine was associated with significantly more fade than either pancuronium or the mixture. During the period of study the fade profile of the mixture was almost identical to that of pancuronium alone. The mixture had the most rapid total onset time (100.3 s), tubocurarine the slowest (135.1 s) and pancuronium was intermediate (124.0 s). The mixture and tubocurarine had similar latent onset times, while the mixture and pancuronium had similar manifest onset times.
Topics: Adult; Drug Combinations; Female; Humans; Male; Middle Aged; Muscle Contraction; Neuromuscular Junction; Pancuronium; Time Factors; Tubocurarine
PubMed: 3994882
DOI: 10.1093/bja/57.5.488 -
British Journal of Anaesthesia Dec 1976The effect of tubocurarine and pancuronium on the initiation or prevention of porcine malignant hyperthermia (MH) was investigated in Pietrain pigs. Tubocurarine 0.6...
The effect of tubocurarine and pancuronium on the initiation or prevention of porcine malignant hyperthermia (MH) was investigated in Pietrain pigs. Tubocurarine 0.6 mg/kg body weight inhibited a suxamethonium-induced response in three pigs, but failed to prevent a fatal halothane-induced response in a further four pigs. Pancuronium 0.2 mg/kg body weight was given to six pigs before a halothane challenge. Three animals developed MH and died; the remainder succembed only after reversal of the neuromuscular blockade. The partial protection afforded by large doses of pancuronium is discussed in relation to the ability of previous muscle activity to influence the sensitivity to halothane.
Topics: Animals; Halothane; Malignant Hyperthermia; Neuromuscular Junction; Pancuronium; Succinylcholine; Swine; Time Factors; Tubocurarine
PubMed: 1023949
DOI: 10.1093/bja/48.12.1135 -
British Journal of Clinical Pharmacology Feb 19781 Contractions of adductor pollicis in unanaesthetized man were elicited by direct and indirect stimulation. Single twitch responses as well as those by a train of four... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
The effect of tubocurarine and suxamethonium on directly and indirectly elicited contractions of skeletal muscle in unanaesthetized man using single and train of four impulses.
1 Contractions of adductor pollicis in unanaesthetized man were elicited by direct and indirect stimulation. Single twitch responses as well as those by a train of four impulses at 2 Hz for 2 s were elicited for indirect stimulation. 2 After a suitable control period, tubocurarine (0.05 mg/kg) or suxamethonium (0.08 mg/kg) was administered intravenously. 3 A stepwise diminution in the train of four impulses was noticed after tubocurarine. Indirectly elicited contractions due to single stimulus and direct muscle stimulation remained unaltered. 4 Partial blockade of transient duration occured after suxamethonium for single as well as train of four stimuli. Directly elicited contractions remained unchanged. The intensity of blockade depended on the rate of injection of suxamethonium. 5 Indirectly elicited contractions by train of four impulses is a reliable and sensitive method for testing neuromuscular blocking drugs in unanaesthetized man.
Topics: Adult; Electric Stimulation; Humans; Muscle Contraction; Succinylcholine; Tubocurarine
PubMed: 619946
DOI: 10.1111/j.1365-2125.1978.tb01613.x -
The Journal of Physiology May 19661. The effects of I.V. injection of tubocurarine (3 mg/kg) and of acute hypotension upon electrocortical activity of cats under sodium pentobarbitone were analysed....
1. The effects of I.V. injection of tubocurarine (3 mg/kg) and of acute hypotension upon electrocortical activity of cats under sodium pentobarbitone were analysed. Technical artifacts associated with changes in brain volume were minimized.2. Initially, the superficial cortical response was reduced by tubocurarine either insignificantly or by 34% or less. Cats bled before injection of tubocurarine showed initially a similar reduction but, occasionally, a severe delayed reduction was found. Any fall in the superficial cortical response started during the secondary rise in B.P., many seconds after the B.P. had reached its lowest initial level. By contrast, spontaneous electrocortical activity was reduced approximately when the peak initial fall of B.P. occurred and it started to recover during the secondary rise in B.P. Reduction of the superficial cortical response could still be elicited after spindling had been suppressed by deep barbiturate anaesthesia. The initial thalamocortical afferent component in somatosensory area I, which was evoked by dorsal column stimulation, was less reduced by injection of tubocurarine than were the post-synaptic positive-negative components.3. The depressant effects of injected tubocurarine upon the superficial cortical response and spindle activity were approximated by rapid arterial bleeding.4. The superficial cortical response was reduced following virtual arrest of the cerebral circulation by acute exsanguination or by acute oil embolization. Such reduction most likely does not depend on systemic transport of inhibitory substances to the brain.5. After injection of tubocurarine the rate of outflow from the superior sagittal sinus was variably reduced during the initial fall in B.P., and often showed a variable, secondary increase. A net deficit in cerebral blood flow was usually present during the period of 80 sec after injection.6. The variability in the effects of injected tubocurarine upon electrocortical activity is attributed to the variability of the net deficit in cerebral blood flow.
Topics: Animals; Cats; Cerebral Cortex; Cerebrovascular Circulation; Cortical Spreading Depression; Electric Stimulation; Electroencephalography; Hypotension; Injections, Intravenous; Tubocurarine
PubMed: 5921537
DOI: 10.1113/jphysiol.1966.sp007901