A non-depolarizing skeletal muscle relaxant similar to TUBOCURARINE. It is used as an anesthesia adjuvant.
A curare alkaloid that is a very potent competitive nicotinic antagonist at the neuromuscular junction.
A synthetic nondepolarizing blocking drug. The actions of gallamine triethiodide are similar to those of TUBOCURARINE, but this agent blocks the cardiac vagus and may cause sinus tachycardia and, occasionally, hypertension and increased cardiac output. It should be used cautiously in patients at risk from increased heart rate but may be preferred for patients with bradycardia. (From AMA Drug Evaluations Annual, 1992, p198)
A muscarinic antagonist used to study binding characteristics of muscarinic cholinergic receptors.
Agents that inhibit the actions of the parasympathetic nervous system. The major group of drugs used therapeutically for this purpose is the MUSCARINIC ANTAGONISTS.
The modification of the reactivity of ENZYMES by the binding of effectors to sites (ALLOSTERIC SITES) on the enzymes other than the substrate BINDING SITES.
One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for MUSCARINE over NICOTINE. There are several subtypes (usually M1, M2, M3....) that are characterized by their cellular actions, pharmacology, and molecular biology.

Interactions of alcuronium, TMB-8, and other allosteric ligands with muscarinic acetylcholine receptors: studies with chimeric receptors. (1/14)

A series of ligands that allosterically modulate the binding of classical ligands to muscarinic receptors was evaluated at wild-type and chimeric receptors. All of the ligands studied had highest affinity toward the M(2) subtype and lowest affinity toward the M(5) subtype. The chimeric receptors were mostly M(5) sequence; the amount of M(2) sequence ranged from about 6 to just under 30%. Alcuronium and TMB-8 had much higher affinity for the chimeric receptor that included the M(2) second outer loop of the receptor plus flanking regions of TM4 and TM5 than for any of the other chimeric receptors (the affinities of which remained similar to that of the M(5) subtype). However, this chimera retained the negative cooperativity between alcuronium and the classical antagonist N-methylscopolamine that is characteristic of M(5) (these ligands are positively cooperative at M(2)). Verapamil, tetrahydroaminoacridine, and d-tubocurarine were also sensitive to that chimeric substitution, although verapamil and tetrahydroaminoacridine had even higher affinity for a chimera with M(2) sequence in TM7. None of these ligands shared gallamine's sensitivity to a region of the third outer loop, but studies in which obidoxime reversed the allosteric effects of gallamine and other ligands suggested that they nevertheless compete for a common site. In summary, although the present data are consistent with previous studies that have suggested that allosteric ligands bind to the outermost regions of muscarinic receptors, it appears that different allosteric ligands may derive subtype selectivity from different regions of the receptor.  (+info)

Changes of cooperativity between N-methylscopolamine and allosteric modulators alcuronium and gallamine induced by mutations of external loops of muscarinic M(3) receptors. (2/14)

To clarify the involvement of specific domains of muscarinic receptors in the action of allosteric modulators, muscarinic M(3) receptors (on which allosteric interactions are weak) were genetically modified to become more similar to M(2) receptors (on which allosteric interactions are strong) and were expressed in COS-7 cells. Affinity for allosteric modulator gallamine was enhanced 25- to 50-fold by modifications of the third external loop (o3) and the negative effect of gallamine on the affinity for classical antagonist N-[(3)H]methylscopolamine ([(3)H]NMS) was augmented. Affinity for alcuronium became 3-fold higher after the o3 loop of M(3) receptors was made identical with the o3 loop of M(2) receptors, and alcuronium acquired positive influence on the affinity for [(3)H]NMS. This is the first instance of inducing positive cooperativity on muscarinic receptors by genetic manipulation. Transferring whole o2 loop from M(2) to M(3) receptors substantially enhanced affinities for gallamine and alcuronium without augmenting their negative action on [(3)H]NMS binding. In contrast, effects of simply adding two negative charges into the o2 loop of M(3) receptors were small. Removal of Arg from o1 loop abolished the negative effect of gallamine but not of alcuronium on [(3)H]NMS binding at equilibrium. Data point to an important role of o3 loop in the mechanism of the positive and negative cooperativity between [(3)H]NMS and alcuronium and gallamine, respectively, and in the binding of both modulators to M(2) receptors and reveal independence between mutation-induced changes in the affinity for a modulator and in the magnitude and direction of the allosteric effect of the modulator.  (+info)

Allosteric modulation of muscarinic receptor signaling: alcuronium-induced conversion of pilocarpine from an agonist into an antagonist. (3/14)

Previous studies on allosteric interactions at muscarinic receptors have often focused on ligand-receptor binding interactions, because ligand binding seemed to reflect functional consequences. The prototypal allosteric agent alcuronium is known to bind with similar affinity to the M(2) subtype of muscarinic acetylcholine receptors whether or not the receptors are occupied by the agonist pilocarpine. To determine allosteric modulation of receptor signaling by alcuronium, the effects of pilocarpine were measured in contracting guinea pig left atria and on G-protein coupling in M(2)-transfected Chinese hamster ovary (CHO) cell membranes. Alcuronium dose-dependently suppressed pilocarpine-induced reduction of isometric contraction force in atria (pIC(50, Alc) = 5.63) without any effect on the EC(50) of pilocarpine, consistent with an allosteric mechanism. In contrast, alcuronium shifted the concentration-effect curve of the agonist oxotremorine M to the right without affecting the maximal effect, in a formally competitive manner (pK(A, Alc) = 5.54). If pilocarpine remained receptor bound in the presence of alcuronium, this indicates that pilocarpine can no longer act as an agonist. In support of this hypothesis, pilocarpine acted as a competitive antagonist against oxotremorine M in the presence of 10 microM alcuronium. Measuring guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding in CHO-M(2) membranes yielded similar results. Alcuronium suppressed pilocarpine-induced stimulation of [(35)S]GTPgammaS binding (pIC(50, Alc) = 5.47) without shift in EC(50), whereas it competitively shifted the response to oxotremorine M (pK(A, Alc) = 5.97). [(3)H]Oxotremorine M binding data corresponded with the functional findings. In conclusion, alcuronium converted the agonist pilocarpine into an antagonist-a novel type of functional allosteric interaction.  (+info)

Regulation of M2 muscarinic acetylcholine receptor expression and signaling by prolonged exposure to allosteric modulators. (4/14)

The effects of prolonged exposure of M(2) muscarinic acetylcholine receptors (mAChRs), stably expressed in Chinese hamster ovary cells, to the allosteric modulators gallamine, alcuronium, and heptane-1,7-bis (dimethyl-3'-phthalimidopropyl)-ammonium bromide (C(7)/3'-phth) were compared with the effects of the agonist carbachol (CCh) and antagonists atropine and N-methylscopolamine (NMS). Intact cell saturation binding assays using [(3)H]NMS found that pretreatment of the cells for 24 h with CCh caused a significant down-regulation of receptor number, whereas atropine, NMS, and all three allosteric modulators caused receptor up-regulation. Functional assays using a cytosensor microphysiometer to measure whole-cell metabolic rate found no acute effects of gallamine on receptor signaling, whereas atropine seemed to behave as an inverse agonist. Pretreatment of the cells with gallamine (20 microM) or atropine (20 nM) resulted in a significant enhancement of the maximal effect evoked by CCh. In contrast, CCh (100 microM) pretreatment resulted in a significant reduction in maximal receptor signaling capacity. Time-course experiments revealed that the effects of atropine and gallamine on receptor up-regulation are only visualized after at least 12-h ligand exposure, compared with the more rapid effects of CCh, which achieve steady-state down-regulation within 90 min. Additional experiments monitoring CCh-mediated M(2) mAChR internalization in the presence of gallamine revealed that part of the mechanism underlying the effects of the modulator on receptor expression may involve a change in receptor internalization properties. These findings suggest that, like orthosteric ligands, G protein-coupled receptor allosteric modulators also are able to mediate long-term effects on receptor regulation.  (+info)

Interaction of competitive antagonists: the anti-curare action of hexamethonium and other antagonists at the skeletal neuromuscular junction. (5/14)

1. In the rat isolated diaphragm preparation hexamethonium and other low potency competitive antagonists of acetylcholine (ACh), including gallamine and hyoscine butylbromide, reverse block by the potent antagonists tubocurarine, pancuronium and alcuronium. 2. In the presence of tubocurarine, hexamethonium increases the amplitude of the end-plate potential without increasing the quantal content. It enhances the response to ACh applied iontophoretically to the end-plate but does not enhance the response to ACh applied in the bath. 3. The anti-curare effect of hexamethonium is abolished in the diaphragm of the rat, guinea-pig and mouse by inhibitors of acetylcholinesterase. The effect is not observed in the indirectly stimulated toad sartorius muscle. 4. The effect is explained if tubocurarine does not dissociate appreciably in the time taken for ACh to achieve high occupancy of receptors, so that a fraction of receptors is completely excluded from occupation by ACh. Equilibration with hexamethonium reduces the fraction excluded by tubocurarine and the transmitter now competes with hexamethonium for more receptors and produces a larger response. 5. On the basis of this explanation the half-time for dissociation of tubocurarine must be about 1 millisecond. It follows that tubocurarine does not act competitively with ACh at synapses when transmitter action is sufficiently brief, and that its binding to the receptor is probably diffusion-limited.  (+info)

The impact of orthosteric radioligand depletion on the quantification of allosteric modulator interactions. (6/14)

 (+info)

Measurement of functional residual capacity by sulfur hexafluoride washout. (7/14)

Measurement of functional residual capacity (FRC) by the open-circuit multiple breath tracer gas washout technique is an established method. A system based upon washout of sulfur hexafluoride (SF6) during mechanical ventilation is described. The central unit in the system is a sensitive and rapid-response infrared SF6 analyzer. SF6 is washed in until the alveolar concentration of SF6 is 0.5%, a concentration so low that the supply of other gases is hardly influenced. During washout, the flow of SF6 from the lungs is calculated by a computer every 10 ms from signals representing expiratory flow and SF6 concentration. The total volume of SF6, washed out, is calculated by integration of SF6 flow. Since the alveolar concentration at the end of washin is known, the lung volume may be obtained. The measurement procedure is highly automated and the result is presented by the computer immediately after washout. Accurate and reproducible results in model lung tests were obtained during air and N2O/O2 ventilation. Comparison with body plethysmography (FRCBOX) in eight sitting healthy subjects gave the following: FRCSF6 = 7 ml + 0.98 X FRCBOX, r = 0.99. Comparison with nitrogen washout (FRCN2) in five postoperative patients gave the following: FRCSF6 = 59 ml + 0.97 X FRCN2, r = 0.97. FRCSF6 during N2O/O2 ventilation was the same as during air/O2 ventilation in a group of paralyzed patients. The measurement system has not been tested in patients with obstructive lung disease.  (+info)

Alcuronium kinetics in patients undergoing cardiopulmonary bypass surgery. (8/14)

1 The disposition of alcuronium was investigated in 10 patients undergoing surgery involving cardiopulmonary bypass (CPB) and compared with results from a group of non-cardiac patients studied previously. 2 After intravenous administration of a combined bolus and infusion dosage regimen, plasma concentrations fell in a bi-exponential fashion to a mean value of 0.55 micrograms/ml immediately before the start of extracorporeal circulation. 3 During CPB an apparent steady-state of alcuronium was reached immediately after commencement of CPB, however plasma concentrations were some 50% higher than those noted prior to commencement of CPB and those predicted using previous pharmacokinetic data from normal surgical patients. 4 Once CPB was completed and the alcuronium infusion terminated, post-infusion alcuronium plasma concentrations again appeared to decline bi-exponentially with time. 5 Of the pharmacokinetic parameters which were calculated model-independently, the apparent volume of distribution (Vss) was unchanged (329 vs 313 ml/kg) and the elimination half-life (t1/2,z) (532 vs 199 min) was prolonged and the plasma clearance (CL) (0.8 vs 1.34 ml min-1kg-1) markedly reduced in these patients compared to non-cardiac surgical patients. 6 As a result of these changes in alcuronium concentration during CPB and the diminished elimination of alcuronium following CPB, a closer monitoring of neuromuscular function may be necessary in cardiac patients undergoing CPB.  (+info)

... (formerly marketed as Alloferin) is a neuromuscular blocking (NMB) agent, alternatively referred to as a ... The major disadvantage of alcuronium is that it elicits a vagolytic effect produced by a selective atropine-like blockade of ... Maass A, Mohr K (1996). "Opposite effects of alcuronium on agonist and on antagonist binding to muscarinic receptors". Eur J ... Zahn K, Eckstein N, Tränkle C, Sadée W, Mohr K (2002). "Allosteric modulation of muscarinic receptor signaling: alcuronium- ...
Hillier K (2007). "Alcuronium". X Pharm: The Comprehensive Pharmacology Reference. xPharm: The Comprehensive Pharmacology ...
Coleman AJ, Downing JW, Leary WP, Moyes DG (1972). "The immediate cardiovascular effects of pancuronium, alcuronium and ...
Yeung ML, Ng LY, Koo AW (Feb 1979). "Severe bronchospasm in an asthmatic patient following alcuronium and D-tubocurarine". ... as well as alcuronium, pancuronium, vecuronium, and gallamine. Seizures rarely occur. Because atracurium undergoes Hofmann ...
Then, 45 mg alcuronium chloride (Alloferin) or 18 mg pancuronium bromide (Pavulon) is injected. To ensure optimal availability ... In severe hepatitis or cirrhosis of the liver, alcuronium is the agent of first choice. Intravenous administration is the most ...
The Wieland-Gumlich aldehyde has been used in the industrial synthesis of alcuronium chloride (Alloferin) via dimerization. ...
Many other different structures have been used for their muscle relaxant effect such as alcuronium (alloferin), anatruxonium, ...
In 1982, he had his first publication: a letter to the editor suggesting that alcuronium should be used instead of ...
Ingredients such as pancuronium bromide (Pavulon) and alcuronium bromide (Alloferin) can block the acetylcholine receptors of ...
... the type known as ethanol Alcomicin Alconefrinasal Solution alcuronium chloride (INN) Aldactazide Aldactone Aldara (3m), also ...
... alcuronium MeSH D03.132.436.255.847 - tubocurarine MeSH D03.132.436.444 - harmaline MeSH D03.132.436.477 - harmine MeSH D03.132 ... alcuronium MeSH D03.438.473.402.255.847 - tubocurarine MeSH D03.438.473.402.444 - harmaline MeSH D03.438.473.402.477 - harmine ...
... alcuronium MeSH D02.092.877.883 - trimethyl ammonium compounds MeSH D02.092.877.883.077 - betaine MeSH D02.092.877.883.088 - ... alcuronium MeSH D02.675.276.922 - tubocurarine MeSH D02.691.088.030 - arsanilic acid MeSH D02.691.088.040 - arsenamide MeSH ...
M03AA01 Alcuronium M03AA02 Tubocurarine M03AA04 Dimethyltubocurarine M03AB01 Suxamethonium M03AC01 Pancuronium M03AC02 ...
Short acting Mivacurium Rapacuronium Intermediate acting Atracurium Cisatracurium Rocuronium Vecuronium Long acting Alcuronium ...
Acute intermittent porphyria (AIP) is one of the porphyrias, a group of diseases involving defects in heme metabolism and that results in excessive secretion of porphyrins and porphyrin precursors. AIP manifests itself by abdomen pain, neuropathies, and constipation, but, unlike most types of porphyria, patients with AIP do not have a rash.
Acute intermittent porphyria (AIP) is one of the porphyrias, a group of diseases involving defects in heme metabolism and that results in excessive secretion of porphyrins and porphyrin precursors. AIP manifests itself by abdomen pain, neuropathies, and constipation, but, unlike most types of porphyria, patients with AIP do not have a rash.
Acute intermittent porphyria (AIP) is one of the porphyrias, a group of diseases involving defects in heme metabolism and that results in excessive secretion of porphyrins and porphyrin precursors. AIP manifests itself by abdomen pain, neuropathies, and constipation, but, unlike most types of porphyria, patients with AIP do not have a rash.
Alcuronium D3.132.436.255.712.50 D3.132.98.833.50. D3.438.473.402.255.712.50 D3.438.531.85.777.50. D3.438.531.820.687.50. ...
Alcuronium Chloride Narrower Concept UI. M0330741. Registry Number. 490DW6501Y. Terms. Alcuronium Chloride Preferred Term Term ... Alcuronium Chloride Alcuronium Dichloride Allnortoxiferine Alloferin Dialferine Diallylnortoxiferine N,N- ... 91; was see under TOXIFERINE 1975-90; ALLOFERIN was see ALCURONIUM 1978-93. Online Note. use ALCURONIUM to search ALLOFERIN ... Alcuronium Preferred Term Term UI T001332. Date01/01/1999. LexicalTag NON. ThesaurusID ...
6. The effects of brucine and alcuronium on the inhibition of [3H]acetylcholine release from rat striatum by muscarinic ... 3. Subtype selectivity of the positive allosteric action of alcuronium at cloned M1-M5 muscarinic acetylcholine receptors. ... Allosteric modulation of muscarinic receptor signaling: alcuronium-induced conversion of pilocarpine from an agonist into an ...
Alcuronium Chloride Entry term(s). Alcuronium Dichloride Dichloride, Alcuronium Dichloride, N,N-Diallylnortoxiferinium N,N- ... Alcuronium Entry term(s):. Alcuronium Chloride. Alcuronium Dichloride. Allnortoxiferine. Alloferin. Dialferine. ... Alcuronium - Preferred Concept UI. M0000669. Scope note. A non-depolarizing skeletal muscle relaxant similar to TUBOCURARINE. ... Alcuronium Chloride - Narrower Concept UI. M0330741. Preferred term. ...
Alcuronium Chloride Narrower Concept UI. M0330741. Registry Number. 490DW6501Y. Terms. Alcuronium Chloride Preferred Term Term ... Alcuronium Chloride Alcuronium Dichloride Allnortoxiferine Alloferin Dialferine Diallylnortoxiferine N,N- ... 91; was see under TOXIFERINE 1975-90; ALLOFERIN was see ALCURONIUM 1978-93. Online Note. use ALCURONIUM to search ALLOFERIN ... Alcuronium Preferred Term Term UI T001332. Date01/01/1999. LexicalTag NON. ThesaurusID ...
Aclatonium napadisilate; Alcuronium (chloride); Atracurium besilate; Carbolonium (bromide); Curare, curarine; Cyclobenzaprine; ...
Alcuronium D3.132.436.255.712.50 D3.132.98.833.50. D3.438.473.402.255.712.50 D3.438.531.85.777.50. D3.438.531.820.687.50. ...
C65219 S56PQL4N1V ALCLOMETASONE DIPROPIONATE C47385 18B8O9DQA2 ALCLOXA C76518 3K9958V90M ALCOHOL C2190 490DW6501Y ALCURONIUM ...
... and alcuronium; saturation binding: W84) were consistent with a competitive mode of action between the fluorescent probes and ...
The Wieland-Gumlich aldehyde has been used in the industrial synthesis of alcuronium chloride (Alloferin) via dimerization ...
D12.644.504.111 Alcuronium D3.132.436.255.712.50 D3.132.98.833.50 D3.438.473.402.255.712.50 D3.438.531.85.777.50 D3.438.531.820 ...
Alcuronium D3.438.531.85.777.50 D3.633.100.531.85.777.50 D3.438.531.820.687.50 D3.633.100.531.820.687.50 Aldosterone D4.808. ...
E945.2 Skeletal muscle relaxants Alcuronium chloride Suxamethonium chloride E945.3 Other and unspecified drugs acting on ...
Acute intermittent porphyria (AIP) is one of the porphyrias, a group of diseases involving defects in heme metabolism and that results in excessive secretion of porphyrins and porphyrin precursors. AIP manifests itself by abdomen pain, neuropathies, and constipation, but, unlike most types of porphyria, patients with AIP do not have a rash.
Alcuronium (substance). Code System Preferred Concept Name. Alcuronium (substance). Concept Status. Published. ...
Alcuronium D3.132.436.255.712.50 D3.132.98.833.50. D3.438.473.402.255.712.50 D3.438.531.85.777.50. D3.438.531.820.687.50. ...
... corilagin audio fomocaine paniculata listserv pimecrolimus mastoparan macrogol gbua itgb1bp1 koumine sphingomyelin alcuronium ...
Alcuronium D3.132.436.255.712.50 D3.132.98.833.50. D3.438.473.402.255.712.50 D3.438.531.85.777.50. D3.438.531.820.687.50. ...
Alcuronium D3.132.436.255.712.50 D3.132.98.833.50. D3.438.473.402.255.712.50 D3.438.531.85.777.50. D3.438.531.820.687.50. ...
Alcuronium D3.132.436.255.712.50 D3.132.98.833.50. D3.438.473.402.255.712.50 D3.438.531.85.777.50. D3.438.531.820.687.50. ...
Alcuronium D3.132.436.255.712.50 D3.132.98.833.50. D3.438.473.402.255.712.50 D3.438.531.85.777.50. D3.438.531.820.687.50. ...
Alcuronium D3.132.436.255.712.50 D3.132.98.833.50. D3.438.473.402.255.712.50 D3.438.531.85.777.50. D3.438.531.820.687.50. ...
Alcuronium D3.132.436.255.712.50 D3.132.98.833.50. D3.438.473.402.255.712.50 D3.438.531.85.777.50. D3.438.531.820.687.50. ...
Alcuronium D3.132.436.255.712.50 D3.132.98.833.50. D3.438.473.402.255.712.50 D3.438.531.85.777.50. D3.438.531.820.687.50. ...
Alcuronium D3.132.436.255.712.50 D3.132.98.833.50. D3.438.473.402.255.712.50 D3.438.531.85.777.50. D3.438.531.820.687.50. ...
Alcuronium D3.132.436.255.712.50 D3.132.98.833.50. D3.438.473.402.255.712.50 D3.438.531.85.777.50. D3.438.531.820.687.50. ...
Alcuronium D3.132.436.255.712.50 D3.132.98.833.50. D3.438.473.402.255.712.50 D3.438.531.85.777.50. D3.438.531.820.687.50. ...
Alcuronium D3.132.436.255.712.50 D3.132.98.833.50. D3.438.473.402.255.712.50 D3.438.531.85.777.50. D3.438.531.820.687.50. ...
  • 3. Subtype selectivity of the positive allosteric action of alcuronium at cloned M1-M5 muscarinic acetylcholine receptors. (nih.gov)