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The Journal of Physiology Jul 19701. Repeated flashes of diffuse light were presented to the cat's eye over long periods of time (hours) while the mixed ganglion cell response was recorded from single...
1. Repeated flashes of diffuse light were presented to the cat's eye over long periods of time (hours) while the mixed ganglion cell response was recorded from single axons in the optic tract. This was done for cats receiving gallamine triethiodide intravenously and for cats who did not receive the drug.2. All responses were transformed into instantaneous pulse density tracings. Such tracings from control and gallamine cells were compared to observe possible effects of gallamine: (a) the shape (time course) did not change during gallamine administration; (b) maximum firing frequency, total number of spikes and latency was measured for both the on- and the off-component on the pulse density tracings and plotted versus time. Statistical methods failed to reveal any difference between the manner in which these response features of control cells and of gallamine cells varied with time.
Topics: Action Potentials; Animals; Axons; Cats
PubMed: 5499790
DOI: 10.1113/jphysiol.1970.sp009142 -
British Journal of Anaesthesia Apr 1978The fate of gallamine triethiodide has been investigated in patients undergoing cholecystectomy with choledochostomy (group I), pelvic operations (group II) and...
The fate of gallamine triethiodide has been investigated in patients undergoing cholecystectomy with choledochostomy (group I), pelvic operations (group II) and orthopaedic operations (group III). Following a single i.v. injection of gallamine 2.5 mg kg(-1) the disappearance of the drug from the serum occurred in three phases with half-lives of less than 5, 30, 138 min, less than 5, 39, 141 and less than 5, 48, 144 min in the respective groups. Twenty-four hours after injection the renal excretion of the unchanged drug was 53% (15-100%) of the administered dose in group I, 67% (40-90%) in group II and 95% (89-100%) in group III. The biliary excretion of gallamine appeared to be negligible in man. The relationship between renal excretion and duration of action of gallamine, and the influence of some intraoperative factors on drug disposition, are discussed.
Topics: Adult; Bile; Female; Gallamine Triethiodide; Half-Life; Humans; Kidney; Liver; Male; Middle Aged; Time Factors
PubMed: 656250
DOI: 10.1093/bja/50.4.345 -
British Journal of Pharmacology Jun 19891. The effect of muscarinic antagonists considered to be selective for M1 receptors (pirenzepine) and for M2 receptors (gallamine) were studied on bronchoconstriction...
1. The effect of muscarinic antagonists considered to be selective for M1 receptors (pirenzepine) and for M2 receptors (gallamine) were studied on bronchoconstriction and bradycardia elicited by stimulation of the vagal nerves and by i.v. acetylcholine (ACh) in anaesthetized rabbits. 2. Pirenzepine was equipotent as an antagonist of ACh-induced responses at postjunctional muscarinic receptors in the heart, lung and blood vessels, whereas gallamine was at least ten times less potent at pulmonary and vascular muscarinic receptors. Thus, gallamine never caused complete inhibition of bronchoconstrictor or hypotensive responses to i.v. ACh, whereas doses of pirenzepine in excess of 1 mumol kg-1 abolished all muscarinic responses. 3. In the lung, both antagonists inhibited bronchoconstriction caused by vagal stimulation and ACh-induced bronchoconstriction to the same extent (pirenzepine, mean ED50 65 +/- 22 and, 130 +/- 28 nmol kg-1 respectively; gallamine, ED50 greater than 10,000 nmol kg-1 for both responses). Enhancement of vagally-induced bronchoconstriction was never observed. 4. In the heart, however, both pirenzepine and gallamine were ten times less potent as antagonists of vagally-induced bradycardia than of ACh-induced bradycardia. This differential blockade was unaltered by propranolol (1 mg kg-1) pretreatment. 5. It is concluded that there is no evidence for M1 or M2 muscarinic receptors in the pulmonary innervation of the rabbit and the potency of the antagonists in abolishing in abolishing vagally-induced bronchoconstriction was consistent with blockade of M3 muscarinic receptors on airway smooth muscle. 6. The results suggest that M2 muscarinic receptors may exert an inhibitory effect on transmission in the parasympathetic nerves innervating the heart in the rabbit. Blockade of such neuronal receptors would increase transmitter output to the atrial cells and explain the low potency of both antagonists in abolishing vagally-induced bradycardia in the rabbit.
Topics: Animals; Electric Stimulation; Female; Gallamine Triethiodide; Heart; Heart Rate; In Vitro Techniques; Lung; Male; Muscle, Smooth, Vascular; Myocardium; Neuromuscular Junction; Parasympatholytics; Pirenzepine; Rabbits; Receptors, Muscarinic; Vagus Nerve
PubMed: 2758229
DOI: 10.1111/j.1476-5381.1989.tb11979.x -
British Journal of Anaesthesia Mar 1970
Review
Topics: Acid-Base Equilibrium; Androstanes; Animals; Anura; Blood Pressure; Carbon Dioxide; Cats; Cholinesterase Inhibitors; Cholinesterases; Drug Hypersensitivity; Drug Synergism; Female; Gallamine Triethiodide; Ganglionic Blockers; Heart Arrest; Histamine Release; Humans; Hyperkalemia; Intraocular Pressure; Intubation, Intratracheal; Maternal-Fetal Exchange; Neostigmine; Neuromuscular Depolarizing Agents; Pregnancy; Propanidid; Succinylcholine; Tubocurarine; gamma-Globulins
PubMed: 4193499
DOI: 10.1093/bja/42.3.235 -
Anesthesiology 1965
Topics: Electromyography; Female; Gallamine Triethiodide; Humans; Middle Aged
PubMed: 5844276
DOI: 10.1097/00000542-196511000-00025 -
Biochemistry Jun 2012At least four allosteric sites have been found to mediate the dose-dependent effects of gallamine on the binding of [(3)H]quinuclidinylbenzilate (QNB) and...
At least four allosteric sites have been found to mediate the dose-dependent effects of gallamine on the binding of [(3)H]quinuclidinylbenzilate (QNB) and N-[(3)H]methylscopolamine (NMS) to M(2) muscarinic receptors in membranes and solubilized preparations from porcine atria, CHO cells, and Sf9 cells. The rate of dissociation of [(3)H]QNB was affected in a bell-shaped manner with at least one Hill coefficient (n(H)) greater than 1, indicating that at least three allosteric sites are involved. The level of binding of [(3)H]QNB was decreased in a biphasic manner, revealing at least two allosteric sites; binding of [(3)H]NMS was affected in a triphasic, serpentine manner, revealing at least three sites, and values of n(H) >1 pointed to at least four sites. Several lines of evidence indicate that all effects of gallamine were allosteric in nature and could be observed at equilibrium. The rates of equilibration and dissociation suggest that the receptor was predominately oligomeric, and the heterogeneity revealed by gallamine can be attributed to differences in its affinity for the constituent protomers of a tetramer. Those differences appear to arise from inter- and intramolecular cooperativity between gallamine and the radioligand.
Topics: Allosteric Regulation; Allosteric Site; Animals; CHO Cells; Cholinergic Antagonists; Cricetinae; Gallamine Triethiodide; Kinetics; Muscarinic Antagonists; N-Methylscopolamine; Protein Subunits; Quinuclidinyl Benzilate; Receptor, Muscarinic M2; Sf9 Cells; Solubility; Swine
PubMed: 22551249
DOI: 10.1021/bi3000287 -
The FEBS Journal Apr 2009The hydrolysis of acetylthiocholine by acetylcholinesterase from Electrophorus electricus was investigated in the presence of the inhibitors tacrine, gallamine and...
The hydrolysis of acetylthiocholine by acetylcholinesterase from Electrophorus electricus was investigated in the presence of the inhibitors tacrine, gallamine and compound 1. The interaction of the enzyme with the substrate and the inhibitors was characterized by the parameters K(I), alpha', b or beta, K(m) and V(max), which were determined directly and simultaneously from nonlinear Michaelis-Menten plots. Tacrine was shown to act as a mixed-type inhibitor with a strong noncompetitive component (alpha' approximately 1) and to completely block deacylation of the acyl-enzyme. In contrast, acetylcholinesterase inhibition by gallamine followed the 'steric blockade hypothesis', i.e. only substrate association to as well as substrate/product dissociation from the active site were reduced in the presence of the inhibitor. The relative efficiency of the acetylcholinesterase-gallamine complex for the catalysis of substrate conversion was determined to be 1.7-25% of that of the free enzyme. Substrate hydrolysis and the inhibition of acetylcholinesterase were also investigated in the presence of 6% acetonitrile, and a competitive pseudo-inhibition was observed for acetonitrile (K(I) = 0.25 m). The interaction of acetylcholinesterase with acetonitrile and tacrine or gallamine resulted in a seven- to 10-fold increase in the K(I) values, whereas the principal mode of inhibition was not affected by the organic solvent. The determination of the inhibitory parameters of compound 1 in the presence of acetonitrile revealed that the substance acts as a hyperbolic mixed-type inhibitor of acetylcholinesterase. The complex formed by the enzyme and the inhibitor still catalysed product formation with 8.7-9.6% relative efficiency.
Topics: Acetonitriles; Acetylcholinesterase; Acetylthiocholine; Animals; Cholinesterase Inhibitors; Electrophorus; Gallamine Triethiodide; Hydrolysis; Kinetics; Tacrine
PubMed: 19292865
DOI: 10.1111/j.1742-4658.2009.06957.x -
The Journal of Physiology Feb 19821. Internal gallamine triethiodide (Flaxedil) modifies Na+ channel kinetics in Myxicola axons but does not alter K+ conductance. The drug has no effect externally. 2....
1. Internal gallamine triethiodide (Flaxedil) modifies Na+ channel kinetics in Myxicola axons but does not alter K+ conductance. The drug has no effect externally. 2. Gallamine initially increases the leakage-conductance, but this effect completely reverses within 30 min despite the maintained presence of drug. 3. During step depolarizations to membrane potentials less than -10 mV, gallamine slows the rate of Na+ inactivation, but all channels which have opened can still inactivate. During depolarizations to more positive potentials, gallamine-modified Na+ currents show a biphasic decline, and at VM greater than -10 mV, Na+ inactivation is incomplete as evidenced by the large Na+ tail currents which follow pulses sufficiently long to have allowed complete inactivation of normal Na+ channels. The tail currents are slower than normal Na+ tails, and exhibit a pronounced hook. With gallamine, the fraction of Na+ channels which do not inactivate increases sigmoidally over the range 0 mV to +80 mV. 4. For VM greater than ENa, gallamine almost completely blocks outward Na+ currents. The block is determined by the direction of Na+ current, rather than the absolute membrane potential. 5. Gallamine has no effect upon the rate of Na+ channel activation, the maximum Na+ conductance, the steady-state Na+ inactivation curve, or the rate of development or removal of inactivation by prepulses. 6. Gallamine eliminated physiological immobilization of intramembrane charge movements (QOFF and QON) and does not itself induce immobilization. Thus, in the presence of gallamine, QOFF following long pulses is the same as QOFF following short pulses.
Topics: Animals; Axons; Gallamine Triethiodide; In Vitro Techniques; Ion Channels; Kinetics; Membrane Potentials; Polychaeta; Potassium; Sodium
PubMed: 6284914
DOI: 10.1113/jphysiol.1982.sp014066 -
Biochemical Pharmacology Oct 2021Endogenous neurosteroids and their synthetic analogues-neuroactive steroids-have been found to bind to muscarinic acetylcholine receptors and allosterically modulate...
Endogenous neurosteroids and their synthetic analogues-neuroactive steroids-have been found to bind to muscarinic acetylcholine receptors and allosterically modulate acetylcholine binding and function. Using radioligand binding experiments we investigated their binding mode. We show that neuroactive steroids bind to two binding sites on muscarinic receptors. Their affinity for the high-affinity binding site is about 100 nM. Their affinity for the low-affinity binding site is about 10 µM. The high-affinity binding occurs at the same site as binding of steroid-based WIN-compounds that is different from the common allosteric binding site for alcuronium or gallamine that is located between the second and third extracellular loop of the receptor. This binding site is also different from the allosteric binding site for the structurally related aminosteroid-based myorelaxants pancuronium and rapacuronium. Membrane cholesterol competes with neurosteroids/neuroactive steroids binding to both high- and low-affinity binding site, indicating that both sites are oriented towards the cell membrane..
Topics: Allosteric Regulation; Androstanes; Androstenes; Animals; Benzimidazoles; Binding Sites; CHO Cells; Cholesterol; Cricetinae; Cricetulus; Gallamine Triethiodide; Humans; Neuromuscular Nondepolarizing Agents; Neurosteroids; Receptors, Muscarinic; Vecuronium Bromide
PubMed: 34324870
DOI: 10.1016/j.bcp.2021.114699 -
British Medical Journal Apr 1951
Topics: Bis-Trimethylammonium Compounds; Convulsive Therapy; Decamethonium Compounds; Gallamine Triethiodide; Humans; Tubocurarine
PubMed: 14821551
DOI: 10.1136/bmj.1.4711.857