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British Medical Journal Apr 1947
Topics: Blood Pressure; Blood Pressure Determination; Humans; Tubocurarine
PubMed: 20343512
DOI: 10.1136/bmj.1.4503.579-a -
Anaesthesia 1979Seventy-six patients in whom sodium nitroprusside was administered in order to induce hypotension received either 0.2 mg/kg tubocurarine or 0.04 mg/kg pancuronium... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Seventy-six patients in whom sodium nitroprusside was administered in order to induce hypotension received either 0.2 mg/kg tubocurarine or 0.04 mg/kg pancuronium bromide. The duration of action of these two drugs was assessed. In contrast to previous studies in the dog, sodium nitroprusside, given concurrently with either tubocurarine or pancuronium bromide, did not result in significantly prolonged neuromuscular blockade (33.0 vs 28.6 min for tubocurarine and 39.3 vs 39.6 min for pancuronium bromide; P greater than 0.1). These findings suggest that the prolonged neuromuscular blockade which is sometimes associated with trimetaphan-induced hypotension in man, is not encountered with sodium nitroprusside.
Topics: Adolescent; Adult; Aged; Arthroplasty; Drug Interactions; Ferricyanides; Humans; Hypotension, Controlled; Middle Aged; Neuromuscular Junction; Nitroprusside; Pancuronium; Prospective Studies; Synaptic Transmission; Time Factors; Tubocurarine
PubMed: 231914
DOI: 10.1111/j.1365-2044.1979.tb06248.x -
Anesthesiology Aug 1983This study was designed to compare the effects of three neuromuscular blocking agents, in a clinically relevant dose range, on the regional distribution of blood flow... (Comparative Study)
Comparative Study
This study was designed to compare the effects of three neuromuscular blocking agents, in a clinically relevant dose range, on the regional distribution of blood flow measured with 15-microns radioactive microspheres in anesthetized, optimally ventilated cats. d-Tubocurarine (400, 800, and 1,600 micrograms X kg-1) caused hypotension and a decrease in ascending aortic blood flow. Pancuronium (20, 40, and 80 micrograms X kg-1) only caused a moderate tachycardia, while vecuronium (40, 80, and 160 micrograms X kg-1) was devoid of any systemic hemodynamic effect. Neither pancuronium nor vecuronium caused major changes in regional blood flows. On the other hand, d-tubocurarine increased blood flow to the stomach but decreased that to the kidneys, liver, skin, spleen, intestine, and adrenal glands. These effects of d-tubocurarine show a striking resemblance to those elicited by the infusion of histamine. Blood flow to the nerve-stimulated tibialis anterior muscle, which was about six times that of the unstimulated muscle, was decreased significantly by all three neuromuscular blockers. In conclusion, the results clearly show that, while d-tubocurarine produces major cardiovascular disturbances, pancuronium and, in particular, vecuronium do not cause serious changes in systemic and regional hemodynamics in doses that are two to four times the ED90 for neuromuscular blocking action.
Topics: Animals; Blood Gas Analysis; Cats; Female; Hemodynamics; Male; Muscles; Neuromuscular Nondepolarizing Agents; Pancuronium; Regional Blood Flow; Tubocurarine; Vascular Resistance; Vecuronium Bromide
PubMed: 6135374
DOI: 10.1097/00000542-198308000-00006 -
Anesthesiology Nov 1979To compare the pharmacokinetics of d-tubocurarine and metocurine in man, concentrations of 3H-d-tubocurarine and 14C-metocurine (0,0,N-trimethyl-tubocurarine) in plasma,... (Comparative Study)
Comparative Study
To compare the pharmacokinetics of d-tubocurarine and metocurine in man, concentrations of 3H-d-tubocurarine and 14C-metocurine (0,0,N-trimethyl-tubocurarine) in plasma, urine and bile were determined after intravenous administration of d-tubocurarine, 0.15 mg/kg (five patients), and metocurine, 0.05 mg/kg (five patients), in patients anesthetized with thiopental and nitrous oxide for cholecystectomy. Plasma disappearances of both drugs were triexponential, with mean terminal half-lives of 346 and 217 min for d-tubocurarine and metocurine, respectively. By ion-pair thin-layer chromatography, no metabolite of either compound was found in urine or bile. Renal excretions 48 hours after injection ranged from 46 to 95 per cent of the dose for d-tubocurarine and from 46 to 58 per cent for metocurine. Mean total-body clearances were 56 and 96 ml/min for d-tubocurarine and metocurine, respectively. Biliary elimination of d-tubocurarine was greater than that of metocurine: within 48 hours 11.8 and 2.1 per cent of the doses were excreted in bile, respectively. The observed differences in total-body clearances and volumes of distribution (V1) may be partly explained by greater protein binding of d-tubocurarine. The results indicate that biliary excretion is an alternative route of elimination for d-tubocurarine only. Also, d-tubocurarine is less dependent on renal excretion for its elimination, and probably is preferable to metocurine for use in patients with renal failure.
Topics: Adult; Aged; Bile; Cholecystectomy; Humans; Kinetics; Middle Aged; Tubocurarine
PubMed: 496054
DOI: 10.1097/00000542-197911000-00007 -
Anesthesiology Sep 1982The pharmacokinetics and pharmacodynamics of d-tubocurarine (dTc) were determined in neonates (0-2 months, n = 7), infants (2-12 months, n = 7), children (1-12 years, n...
The pharmacokinetics and pharmacodynamics of d-tubocurarine (dTc) were determined in neonates (0-2 months, n = 7), infants (2-12 months, n = 7), children (1-12 years, n = 9), and adults (12-30 years, n = 8) during 70% nitrous oxide, 0.58 MAC halothane anesthesia. dTc was administered by infusion, while blood for determination of plasma dTc concentrations was obtained, and the EMG of the adductor pollicis recorded. The plasma dTc concentration at which 50% depression of EMG twitch height occurs (Cpss(50)) was 0.18 +/- 0.09 micrograms/ml in neonates, and 0.27 +/- 0.06 micrograms/ml in infants, both significantly lower than the values of 0.42 +/- 0.14 and 0.53 +/- 0.14 micrograms/ml for children and adults, respectively. The steady-state distribution volume (Vdss) was 0.74 +/- 0.33 l/kg in neonates, significantly greater than the values of 0.52 +/- 0.22, 0.41 +/- 0.12, and 0.30 +/- 0.10 l/kg in infants, children, and adults, respectively. The elimination half-life (t beta 1/2) was 174 +/- 60 min in neonates, significantly longer than the values of 90 +/- 23 and 89 +/- 18 min in children and adults, respectively. Plasma clearance did not differ with age. We also determined D50, the product of Vdss and Cpss(50). D50, the quantity of drug present at steady-state to produce 50% paralysis, did not differ between groups. The authors conclude that during comparable nitrous oxide-halothane anesthesia, neonates and infants have an increased sensitivity to dTc, as determined by CPss(50). However, because of the larger Vdss in younger patients, dose size should not differ with age. In addition, because of the longer t beta 1/2 in neonates, second and subsequent doses should be required at less frequent intervals.
Topics: Adolescent; Adult; Aging; Anesthesia, General; Child; Child, Preschool; Electromyography; Half-Life; Halothane; Humans; Infant; Infant, Newborn; Kinetics; Models, Biological; Nitrous Oxide; Tubocurarine
PubMed: 7114542
DOI: 10.1097/00000542-198209000-00009 -
Scientific Reports Oct 2023Drug designing is high-priced and time taking process with low success rate. To overcome this obligation, computational drug repositioning technique is being promptly...
Drug designing is high-priced and time taking process with low success rate. To overcome this obligation, computational drug repositioning technique is being promptly used to predict the possible therapeutic effects of FDA approved drugs against multiple diseases. In this computational study, protein modeling, shape-based screening, molecular docking, pharmacogenomics, and molecular dynamic simulation approaches have been utilized to retrieve the FDA approved drugs against AD. The predicted MADD protein structure was designed by homology modeling and characterized through different computational resources. Donepezil and galantamine were implanted as standard drugs and drugs were screened out based on structural similarities. Furthermore, these drugs were evaluated and based on binding energy (Kcal/mol) profiles against MADD through PyRx tool. Moreover, pharmacogenomics analysis showed good possible associations with AD mediated genes and confirmed through detail literature survey. The best 6 drug (darifenacin, astemizole, tubocurarine, elacridar, sertindole and tariquidar) further docked and analyzed their interaction behavior through hydrogen binding. Finally, MD simulation study were carried out on these drugs and evaluated their stability behavior by generating root mean square deviation and fluctuations (RMSD/F), radius of gyration (Rg) and soluble accessible surface area (SASA) graphs. Taken together, darifenacin, astemizole, tubocurarine, elacridar, sertindole and tariquidar displayed good lead like profile as compared with standard and can be used as possible therapeutic agent in the treatment of AD after in-vitro and in-vivo assessment.
Topics: Humans; Drug Repositioning; Molecular Docking Simulation; Alzheimer Disease; Prognosis; Astemizole; Tubocurarine; Molecular Dynamics Simulation
PubMed: 37865690
DOI: 10.1038/s41598-023-45347-1 -
Anesthesiology Jan 1979The potencies of metocurine and d-tubocurarine for neuromuscular and autonomic blockade and histamine release were determined in cats anesthetized with chloralose and...
The potencies of metocurine and d-tubocurarine for neuromuscular and autonomic blockade and histamine release were determined in cats anesthetized with chloralose and pentobarbital. The autonomic margins of safety of these drugs were determined by measuring the ratios of ED50 for sympathetic block to ED95 for neuromuscular block; ED50 for vagal block to ED95 for neuromuscular block; ED50 for histamine release to ED95 for neuromuscular block. Metocurine is 14 times more potent than d-tubocurarine as a neuromuscular blocking agent in the cat, but its autonomic blocking action is three times weaker than the of d-tubocurarine and its histamine-releasing action is less than half that of d-tubocurarine. The combination of higher neuromuscular blocking potency and weaker autonomic effect gives metocurine a much higher autonomic margin of safety than d-tubocurarine in the cat.
Topics: Animals; Autonomic Nerve Block; Autonomic Nervous System; Cats; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Female; Histamine Release; Male; Neuromuscular Junction; Synaptic Transmission; Tubocurarine
PubMed: 83803
DOI: 10.1097/00000542-197901000-00009 -
Anesthesiology May 1981The pharmacokinetics and effectiveness of edrophonium antagonism of d-tubocurarine neuromuscular blockade were compared with that of neostigmine in surgical patients...
The pharmacokinetics and effectiveness of edrophonium antagonism of d-tubocurarine neuromuscular blockade were compared with that of neostigmine in surgical patients anesthetized with halothane and nitrous oxide. After an intravenous (iv) injection of d-tubocurarine (0.3 mg/kg), the single twitch tension was allowed to return to five per cent of the control level. Edrophonium, 0.5 or 1.0 mg/kg (n = 12), or neostigmine, 0.07 mg/kg (n = 6), was then given iv in combination with atropine, 1.0 mg, as a 2-min controlled infusion. Train-of-four and single twitch tension were followed for 60 min in all patients. Twelve patients were monitored for 90 min, six patients for 120 min, four patients for 150 min, and two patients for 240 min. Blood was sampled intermittently for four hours and assayed for edrophonium or neostigmine using high-pressure liquid chromatography. Edrophonium was found to promptly antagonize the d-tubocurarine blockade. Twitch tension rapidly increased to a plateau (a rate of increase in twitch tension of less than 2 per cent of control per min) which was sustained in all cases. The mean time to plateau for edrophonium was 2.9 +/- 0.21 (+/-SE) min as compared to 6.1 +/- 0.75 min for neostigmine. Neuromuscular blockade did not reappear in any patient. The degree of antagonism of the neuromuscular blockade by neostigmine and edrophonium was not significantly different. Except for a longer distribution half-life, the pharmacokinetic variables for edrophonium did not differ significantly from those for neostigmine. The elimination half-lives of edrophonium and neostigmine were 110 +/- 34 min (mean +/- SD) and 77 +/- 47 min, respectively. The authors therefore conclude that edrophonium, 0.5-1.0 mg/kg, has pharmacokinetic variables comparable to neostigmine and produces prompt, sustained, and effective antagonism of d-tubocurarine neuromuscular blockade.
Topics: Adult; Edrophonium; Humans; Kinetics; Middle Aged; Neostigmine; Neuromuscular Blocking Agents; Tubocurarine
PubMed: 7224209
DOI: 10.1097/00000542-198105000-00009 -
British Journal of Anaesthesia Dec 1982Results from in vitro experiments, using the hypogastric nerve--vas deferens preparation, and the phrenic nerve--hemidiaphragm preparation of the guineapig, have been... (Comparative Study)
Comparative Study
Results from in vitro experiments, using the hypogastric nerve--vas deferens preparation, and the phrenic nerve--hemidiaphragm preparation of the guineapig, have been used to determine the separation between the neuromuscular and ganglionic blocking effects of atracurium and tubocurarine. Regression lines were used to calculate the concentrations of each drug (99% confidence limits) which would produce a 50% blockade (EC50) of ganglionic and neuromuscular transmission. The equipotent molar ratio, using EC50 values, for ganglionic/neuromuscular blockade was 48 for atracurium and 9.4 for tubocurarine.
Topics: Animals; Atracurium; Dose-Response Relationship, Drug; Ganglia, Sympathetic; Guinea Pigs; In Vitro Techniques; Isoquinolines; Muscle Contraction; Neuromuscular Blocking Agents; Neuromuscular Junction; Synaptic Transmission; Tubocurarine
PubMed: 6293522
DOI: 10.1093/bja/54.12.1307 -
The Journal of Biological Chemistry Dec 1995Analogs of d-tubocurarine were used to determine the individual effects of methylation, stereoisomerization, and halogenation of d-tubocurarine on the affinity for each...
Interaction of d-tubocurarine analogs with the Torpedo nicotinic acetylcholine receptor. Methylation and stereoisomerization affect site-selective competitive binding and binding to the noncompetitive site.
Analogs of d-tubocurarine were used to determine the individual effects of methylation, stereoisomerization, and halogenation of d-tubocurarine on the affinity for each of the two acetylcholine (ACh) binding sites of the Torpedo nicotinic acetylcholine receptor (AChR) and for the noncompetitive antagonist site. Eight analogs were synthesized, including three new compounds: 7'-O-methyl-chondocurarine, 12'-O-methyl-chondocurarine, and 13'-bromo-d-tubocurarine. The two ACh sites differ in their affinities for d-tubocurarine by 400-fold, as shown by inhibition of [3H]ACh binding, whereas the affinity ratio for metocurine, the trimethylated derivative of d-tubocurarine, is reduced to 30 due to a decreased affinity for the high affinity site. Binding analysis of five d-tubocurarine analogs demonstrates that methylation of the phenols alone is responsible for the observed changes in affinity. Substitution with bromine or iodine at the 13'-position affected affinity at both sites with a net increase in site selectivity. Stereoisomers of d-tubocurare had decreased affinity for only the high affinity ACh site. Thus, the ring systems, including the 12'- and 13'-positions and the 1-position stereocenter, appear to be important in discriminating between the two ACh binding sites. Desensitization of the AChR was measured by increased affinity for [3H]phencyclidine. Binding to only the single, high affinity acetylcholine binding site, comprised by the alpha gamma-subunits, was required for partial desensitization of the AChR by d-tubocurarine and its analogs. Stronger desensitization, to the same extent observed in the presence of the agonist carbamylcholine, occurred upon binding by iodonated or brominated d-tubocurarine. Interaction of the analogs at the noncompetitive antagonist site of the AChR was also measured by [3H]phencyclidine binding. The bis-tertiary ammonium analogs of either the d- or l-stereoisomers bound to the noncompetitive antagonist binding site of the AChR with 100-fold higher affinity than the corresponding quaternary ammonium analogs.
Topics: Animals; Binding, Competitive; Methylation; Nicotinic Agonists; Nicotinic Antagonists; Phencyclidine; Receptors, Nicotinic; Stereoisomerism; Torpedo; Tritium; Tubocurarine
PubMed: 8537377
DOI: 10.1074/jbc.270.52.31141