Disease relevance of gallamine

• In 14 of our patients, the time course of gallamine concentrations in the plasma before, during, and after CPB was similar to that in normal surgical patients, indicating little or no effect of cardiac disease or CPB [1].
• The antagonistic effects of gallamine on muscarinic receptor-linked responses were investigated in N1E-115 neuroblastoma cells [2].
• Vagally-induced bradycardia was abolished by gallamine, confirming antagonism of the effect of acetylcholine on muscarinic receptors in the heart [3].
• However, gallamine, while an effective antagonist of M2 responses, also has the ability to modify the electrical characteristics of ganglion cells and thus may modify ganglionic transmission by mechanisms other than antagonism of receptors [4].
• 5. The difference between A- and C-fibers could not be accounted for on the basis of the maturity of the neuroma, rate and pattern of ongoing discharge, or use of Flaxedil paralysis [5].

Psychiatry related information on gallamine

• Three of 4 patients with accompanying phantom limb pain noted an increase in pain after the injection of gallamine [6].
• The increase in cataplexy in narcoleptic canines produced by local perfusion with carbachol (10(-4) M) followed by equimolar perfusion with a muscarinic antagonist was rapidly reversed by atropine (muscarinic) and gallamine (M2 muscarinic), partially reversed by 4-DAMP (M3/M1 muscarinic) and completely unaffected by pirenzepine (M1 muscarinic) [7].
• Pirenzepine, an inhibitor of M1 muscarinic receptors, was effective in producing amnesia, whereas gallamine, an M2 receptor inhibitor, did not produce amnesia [8].
• Electrographic variables for determining the states of sleep and wakefulness, the electrocorticogram, lateral geniculate nucleus potentials, and dorsal hippocampal potentials, were recorded before, during and after the administration of gallamine triethiodide to cats with chronically implanted electrodes [9].
• In conscious Wistar rats neuromuscularly paralysed by gallamine, operantly conditioned reduction of heart rate was achieved under both negative and positive reinforcement schedules using the tail shock avoidance or the rewarding brain-stimulations in 20-min test sessions [10].

High impact information on gallamine

• Voltage-clamp studies show that gallamine also directly affects amphibian and mammalian myelinated nerve fibers [11].
• In controls, blockade of neuronal M2 muscarinic receptors by gallamine potentiated vagally induced bronchoconstriction, while in challenged animals this effect was markedly reduced, confirming M2 receptor dysfunction [12].
• The pressor and sympathoexcitatory effects of ouabain in the RVLM were reversed by microinjections of an M2 muscarinic antagonist, gallamine, or digoxin-specific antibody Fab fragments [13].
• To characterize central integration of reflex responses to stimulation of mechanically and chemically sensitive receptors in the heart and lung, male rats (350 to 425 g) were anesthetized (pentobarbital, 50 mg/kg IP) and paralyzed (gallamine triethiodide, 25 mg/kg IV) and then they underwent bilateral sinoaortic denervation [14].
• These changes in SP-LI, mean arterial pressure, and heart rate were virtually abolished when the contractions were repeated after sectioning the L-5-S-2 dorsal and ventral roots or when the electrical stimulation of the ventral roots was repeated after muscle paralysis with gallamine triethiodide [15].

Chemical compound and disease context of gallamine

• To examine the basis of tachycardia seen clinically with some neuromuscular blocking agents, the potencies of d-tubocurarine, dimethyltubocurarine, gallamine, and pancuronium in antagonizing the effects of vagal stimulation on the guinea pig atrial pacemaker were determined and expressed as an ED50 for vagal blockade [16].
• The high affinities of gallamine and pancuronium for the M2 muscarinic receptor are consistent with a mechanism of M2 receptor blockade in relaxant-induced tachycardia [17].
• Domestic swine (13-20 kg) were anesthetized with ketamine (20 mg/kg i.m.) and alpha-chloralose (80 mg/kg i.v.) and given gallamine (4 mg/kg i.v.) to prevent muscle fasciculations [18].
• In normal dorsal root ganglion cells, bethanechol inhibited the Ca(2+) response in a concentration-related fashion, and this inhibition was blocked by the M2 muscarinic receptor antagonist gallamine [19].
• Comparison of gallamine with d-tubocurarine effects on fasciculations after succinylcholine [20].

Biological context of gallamine

• We interpret our data to suggest that gallamine not only competes for [3H]QNB binding sites, but also binds at a secondary site on the receptor, forming a ternary complex with [3H]QNB [21].
• The results suggest that the allosteric site for gallamine binding in the m2 receptor residues at or near the putative third outer domain and that both the EDGE motif and Asp-97 play an essential role in the interaction between the two sites [22].
• For the receptors studied, a good agreement was found between the alpha KdA values calculated from the Schild analysis and the IC50 values for the effect of gallamine on the N-methylscopolamine off-rate [22].
• The two main methods used were (i) Schild analysis of equilibrium binding data and (ii) study of the effect of gallamine on the dissociation kinetics of N-methylscopolamine [22].
• All five (m1-m5) muscarinic receptors are sensitive to allosteric regulation, but gallamine is considerably more potent in slowing the dissociation of N-[3H]methylscopolamine (NMS) from the m2 subtype than from the m3 or m5 subtypes [23].

Anatomical context of gallamine

• These results suggest that dopamine plays a prominent role in mediating the stimulatory effects of d-AMP on the firing rates of a population of globus pallidus cells in gallamine-paralyzed rats [24].
• To this end, the effects of the M2-selective muscarinic receptor antagonists AQ-RA 741 and gallamine were studied on electrical field stimulation-induced twitch contractions of preparations from trachea and from bronchial airways of varying diameter [25].
• Similar results were obtained with muscarinic receptors from the brainstem, but gallamine had only marginal effects on the dissociation of [3H]QNB in the forebrain [26].
• We examined changes in the binding of [3H]NMS to membranes of rat heart atria exposed to various concentrations of a positive allosteric effector (alcuronium or strychnine) and of a negative allosteric effector (gallamine) simultaneously [27].
• Furthermore, AC-42 and gallamine significantly retarded the rate of [(3)H]NMS dissociation from CHO-hM(1) cell membranes, conclusively demonstrating their ability to bind to a topographically distinct site to change M(1) receptor conformation [28].

Associations of gallamine with other chemical compounds

• Binding was sensitive to scyllatoxin, dequalinium, gallamine, and d-tubocurarine but not to charybdotoxin, toxin I, or mast cell degranulating peptide [29].
• Additionally, in the presence of gallamine or pancuronium, [3H]QNB binding sites were no longer homogeneous, and Scatchard plots became nonlinear [21].
• Effects of edrophonium, eserine, decamethonium, d-tubocurarine, and gallamine on the kinetics of membrane-bound and solubilized eel acetylcholinesterase [30].
• In an attempt to locate the allosteric site on muscarinic receptors to which gallamine binds, 21 residues in the putative external loops and loop/transmembrane helix interfaces have been mutated to alanine [31].
• Although gallamine and a number of other compounds have been reported to slow the rate of dissociation of labeled ligands, especially [3H]N-methylscopolamine (NMS), from muscarinic receptors of heart and brain, there has been some dispute as to whether the dissociation of [3H]quinuclidinyl benzilate (QNB) is subject to such allosteric regulation [26].

Gene context of gallamine

• 2. Atropine, 4-diphenylacetoxy-N-methylpiperidine (4-DAMP, a muscarinic M3 antagonist), pirenzepine (a muscarinic M1 antagonist), methoctramine and gallamine (muscarinic M2 antagonists) inhibited the acetylcholine-induced Ca2+ release, with a high affinity for 4-DAMP and atropine and a low affinity for the other antagonists [32].
• The M(1) muscarinic antagonist pirenzepine, the M(2) muscarinic antagonist gallamine, and the M(1)/M(3) muscarinic receptor antagonist N-(3-chloropropyl)-4-piperidinyl diphenylacetate (4-DAMP) also inhibited carbachol-stimulated MAPK activation [33].
• By comparison, gallamine was four- to fivefold less potent in blocking noncardiac M2 muscarinic receptor-mediated inhibition of cyclic AMP formation, with a Ki value of 144 microM [2].
• The peripheral anionic site inhibitors propidium and gallamine were inactive on AChE-associated AAA [34].
• When CB1 receptors were not blocked, oxo-M suppressed IPSCs in a gallamine-resistant manner in cannabinoid-sensitive pairs [35].

Analytical, diagnostic and therapeutic context of gallamine

• Microinjections of either digoxinspecific antibody Fab fragments or gallamine per se significantly decreased baseline MAP and RSNA [13].
• The recombinant protein was water-soluble and glycosylated, and fast protein liquid chromatography analysis showed it to be a monomer. halpha-(1-210) bound (125)I-alpha-bungarotoxin with a high affinity (K(d) = 5.1 +/- 2.4 nm), and this binding was blocked by unlabeled d-tubocurarine and gallamine (K(i) approximately 7.5 mm) [36].
• Kinetics of gallamine, a neuromuscular blocker, were investigated in 22 adult patients undergoing surgery involving cardiopulmonary bypass (CPB) [1].
• Although the mechanism for this rise in gallamine plasma concentrations during and after CPB is not known, computer simulations suggest that it is due to a contraction in blood volume or decreased tissue perfusion during the period of extracorporeal circulation [1].
• M2 muscarinic receptor expression was assessed by Western blotting, and function was assessed by electrical field stimulation of tracheas in the presence/absence of gallamine [37].

References