gallamine triethiodide

Summary

Summary: 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)

Top Publications

  1. Quinn C, Begenisich T. The influence of surface charges on quaternary ammonium block of shaker K+ channels. J Membr Biol. 2001;182:233-43 pubmed
  2. Jakubik J, Bacakova L, Lisa V, El Fakahany E, Tucek S. Activation of muscarinic acetylcholine receptors via their allosteric binding sites. Proc Natl Acad Sci U S A. 1996;93:8705-9 pubmed
    ..This represents a new mechanism of receptor activation...
  3. Dussor G, Helesic G, Hargreaves K, Flores C. Cholinergic modulation of nociceptive responses in vivo and neuropeptide release in vitro at the level of the primary sensory neuron. Pain. 2004;107:22-32 pubmed
  4. Paul M, Kindler C, Fokt R, Dipp N, Yost C. Isobolographic analysis of non-depolarising muscle relaxant interactions at their receptor site. Eur J Pharmacol. 2002;438:35-43 pubmed
  5. Fisher M, Baldo B. Persistence of allergy to anaesthetic drugs. Anaesth Intensive Care. 1992;20:143-6 pubmed
    ..In the absence of evidence of allergy diminishing with time in the majority of patients it would seem wise to avoid drugs responsible for reactions for the rest of the patient's life...
  6. El Moursy S, Shawky H, Abdel Wahab Z, Rashed L. The effect of memantine and levodopa/carbidopa on the responses of phrenic nerve-diaphragm preparations from aged rats. Med Sci Monit. 2009;15:BR339-48 pubmed
    ..This study focuses on the influence of memantine (used in moderate to severe AD) and levodopa/carbidopa (LD/CD) (a cornerstone of Parkinson's disease treatment) on responses of isolated phrenic nerve-diaphragms (IPNDs) of aged male rats...
  7. Hernandez C, Nascimento J, Chaves E, Costa P, Masuda M, Kurtenbach E, et al. Autoantibodies enhance agonist action and binding to cardiac muscarinic receptors in chronic Chagas' disease. J Recept Signal Transduct Res. 2008;28:375-401 pubmed
  8. Ekberg O, Ekman M, Eriksson L, Malm R, Sundman E, Arner A. An in vitro model for studying neuromuscular transmission in the mouse pharynx. Dysphagia. 2009;24:32-9 pubmed publisher
    ..The sensitivity to the neuromuscular blocking agent gallamine of the inferior pharyngeal constrictor was in the same concentration range as that of the diaphragm and soleus muscles...
  9. Zefirov T, Ziyatdinova N, Saifutdinova L, Zefirov A. Cardiac activity and blood pressure in rats during selective blockade of various subtypes of muscarinic cholinoceptors. Bull Exp Biol Med. 2006;141:662-5 pubmed
    ..Our results indicate that muscarinic cholinoceptors play a role in the immediate inhibition of cardiac activity upon vagus nerve stimulation...

More Information

Publications62

  1. Huang X, Ellis J. Mutational disruption of a conserved disulfide bond in muscarinic acetylcholine receptors attenuates positive homotropic cooperativity between multiple allosteric sites and has subtype-dependent effects on the affinities of muscarinic allosteric liga. Mol Pharmacol. 2007;71:759-68 pubmed
  2. Balbaa M, Al Meer J, Al Khal A. Effect of some cardiac and respiratory drugs on succinate-cytochrome c reductase. J Enzyme Inhib Med Chem. 2004;19:343-7 pubmed
    ..5 x 10(-5) and 5.7 x 10(-5)M, respectively. Moreover, neostigmine competitively inhibited the enzyme towards both substrates with Ki values of 1.36 x 10(-5) and 1.50 x 10(-5)M, respectively...
  3. Psaridi Linardaki L, Mamalaki A, Tzartos S. Future therapeutic strategies in autoimmune myasthenia gravis. Ann N Y Acad Sci. 2003;998:539-48 pubmed
    ..Work is in progress for the expression of the extracellular domain of all other muscle AChR subunits. It is expected that their combined use may eliminate the great majority of the anti-AChR antibodies from most MG patients...
  4. Tränkle C, Kostenis E, Mohr K. Muscarinic allosteric modulation: M2/M3 subtype selectivity of gallamine is independent of G-protein coupling specificity. Naunyn Schmiedebergs Arch Pharmacol. 2001;364:172-8 pubmed
    ..24, alphaM2/M3-i3= 30 +/- 2, alphaM3/M2-i2 = 3 +/- 0.7). In conclusion, the different sensitivities of M2 and M3 receptors towards allosteric modulation by gallamine are not related to the G-protein coupling specificity of the receptors...
  5. Franken C, Tränkle C, Mohr K. Testing the specificity of allosteric modulators of muscarinic receptors in phylogenetically closely related histamine H1-receptors. Naunyn Schmiedebergs Arch Pharmacol. 2000;361:107-12 pubmed
    ..2 nM, Bmax=205 fmol/mg protein). Half-maximal reduction was observed at 10 mM for gallamine, 1 mM for alcuronium and 92 microM for W84. In conclusion, the muscarinic modulators have little effect on the histamine H1-receptors...
  6. Sato K, Windisch K, Matko I, Vizi E. Effects of non-depolarizing neuromuscular blocking agents on norepinephrine release from human atrial tissue obtained during cardiac surgery. Br J Anaesth. 1999;82:904-9 pubmed
    ..This action contributes to lowering of heart rate. Therefore, any neuromuscular blocking agent with antimuscarinic actions and capable of increasing the release of NE may produce tachycardia...
  7. Holzgrabe U, Wagener M, Gasteiger J. Comparison of structurally different allosteric modulators of muscarinic receptors by self-organizing neural networks. J Mol Graph. 1996;14:185-93, 217-21 pubmed
    ..A distorted sandwich conformation of W84 is suggested to be the active form. The importance of the MEP for binding of these compounds could be established...
  8. Killingsworth C, Yu M, Robinson N. Evidence for the absence of a functional role for muscarinic M2 inhibitory receptors in cat trachea in vivo: contrast with in vitro results. Br J Pharmacol. 1992;105:263-70 pubmed
    ..This was despite repeated demonstration of muscarinic M2 receptor-mediated limitation of airway constriction of intrathoracic airways in vivo...
  9. King W, Schmidt J. The long latency component of retinotectal transmission: enhancement by stimulation of nucleus isthmi or tectobulbar tract and block by nicotinic cholinergic antagonists. Neuroscience. 1991;40:701-12 pubmed
    ..There is in addition a separate recurrent excitatory circuit in tectum...
  10. Roffel A, Meurs H, Elzinga C, Zaagsma J. No evidence for a role of muscarinic M2 receptors in functional antagonism in bovine trachea. Br J Pharmacol. 1995;115:665-71 pubmed
    ..Furthermore,they stress the importance of taking into account non-cholinergic controls as well as contraction levels in these experiments...
  11. Didier A, Benzarti M, Senft M, Charpin D, Lagier F, Charpin J, et al. Allergy to suxamethonium: persisting abnormalities in skin tests, specific IgE antibodies and leucocyte histamine release. Clin Allergy. 1987;17:385-92 pubmed
  12. Manabe N. The effect of non-depolarizing neuromuscular blocking agents on the release of acetylcholine from the right atrium of the guinea pig. Acta Med Okayama. 1997;51:13-8 pubmed
    ..31 microM. These findings indicate that pancuronium and gallamine enhanced the release of acetylcholine from the atrial parasympathetic nerve, probably by inhibiting presynaptic muscarinic receptors...
  13. Yarosh C, Ashe J, Olito A. Differential effects of the muscarinic M2 antagonists, AF-DX 116 and gallamine, on single neurons of rabbit sympathetic ganglia. Neuropharmacology. 1990;29:735-45 pubmed
  14. Cabadak H, Kan B. Methoctramine and gallamine inhibit PI hydrolysis in guinea-pig gallbladder. Vascul Pharmacol. 2005;43:242-6 pubmed
    ..Our data suggest that M(3) receptors play a major role in stimulation of PI hydrolysis in the guinea-pig gallbladder...
  15. Suga H, Figueroa K, Ehlert F. Use of acetylcholine mustard to study allosteric interactions at the M(2) muscarinic receptor. J Pharmacol Exp Ther. 2008;327:518-28 pubmed publisher
    ..Our results show that measurement of the effects of ligands on the rate of inactivation of the orthosteric site by a small site-directed electrophile is a powerful method for discriminating competitive inhibition from allosterism...
  16. Redka D, Pisterzi L, Wells J. Binding of orthosteric ligands to the allosteric site of the M(2) muscarinic cholinergic receptor. Mol Pharmacol. 2008;74:834-43 pubmed publisher
    ..Ligands generally assumed to be exclusively orthosteric therefore can act at the allosteric site of the M(2) receptor, albeit at comparatively high concentrations...
  17. Yang Z, Biggs D. Muscarinic-receptor functioning in tracheas from normal and ovalbumin-sensitive guinea pigs. Can J Physiol Pharmacol. 1991;69:871-6 pubmed
    ..Changes in post-receptor transduction mechanisms may mediate the increased responsiveness noted in animals from group c...
  18. Bognar I, Wesner M, Fuder H. Muscarine receptor types mediating autoinhibition of acetylcholine release and sphincter contraction in the guinea-pig iris. Naunyn Schmiedebergs Arch Pharmacol. 1990;341:22-9 pubmed
    ..The results are consistent with the idea of M2 muscarine receptors mediating autoinhibition of acetylcholine release in the guinea-pig iris and M3-like receptors inducing the contraction of the sphincter muscle...
  19. Jung R, Katona P. Cardiovascular and respiratory responses to slow ramp carotid sinus pressures in the dog. J Appl Physiol (1985). 1990;68:1465-74 pubmed
  20. Theroux M, Rose J, Iyengar S, Katz M. Succinylcholine pretreatment using gallamine or mivacurium during rapid sequence induction in children: a randomized, controlled study. J Clin Anesth. 2001;13:287-92 pubmed
  21. Huang X, Prilla S, Mohr K, Ellis J. Critical amino acid residues of the common allosteric site on the M2 muscarinic acetylcholine receptor: more similarities than differences between the structurally divergent agents gallamine and bis(ammonio)alkane-type hexamethylene-bis-[dimethyl-(3-. Mol Pharmacol. 2005;68:769-78 pubmed
    ..Thus, gallamine and W84 derive high potency from the same receptor domains (epitopes in o2 and near the junction between o3 and TM7), even though these allosteric agents have quite different structures...
  22. Seeger T, Alzheimer C. Muscarinic activation of inwardly rectifying K(+) conductance reduces EPSPs in rat hippocampal CA1 pyramidal cells. J Physiol. 2001;535:383-96 pubmed
    ..7. We link the observed reduction of postsynaptic potentials to the cholinergic activation of a GIRK conductance, which serves to partially shunt excitatory synaptic input...
  23. Avlani V, McLoughlin D, Sexton P, Christopoulos A. The impact of orthosteric radioligand depletion on the quantification of allosteric modulator interactions. J Pharmacol Exp Ther. 2008;325:927-34 pubmed publisher
    ..These results have important implications for the quantification of allosteric modulator actions in binding-based discovery assays...
  24. Suzuki A, Shimura M. Changes in blood pressure induced by electrical stimulation of the femur in anesthetized rats. Auton Neurosci. 2010;158:39-43 pubmed publisher
    ..The excitatory response properties at the propriospinal level are modified into an inhibitory response by supraspinal structures...
  25. Kupchik Y, Barchad Avitzur O, Wess J, Ben Chaim Y, Parnas I, Parnas H. A novel fast mechanism for GPCR-mediated signal transduction--control of neurotransmitter release. J Cell Biol. 2011;192:137-51 pubmed publisher
    ..Our results suggest that, in addition to Ca(2+) influx, charge movement in GPCRs is also necessary for release control...
  26. Oenema T, Mensink G, Smedinga L, Halayko A, Zaagsma J, Meurs H, et al. Cross-talk between transforming growth factor-?? and muscarinic M? receptors augments airway smooth muscle proliferation. Am J Respir Cell Mol Biol. 2013;49:18-27 pubmed publisher
    ..We conclude that prolonged exposure to TGF-?? enhances ASM cell proliferation, which is mediated by extracellular matrix-integrin interactions, and which can be enhanced by muscarinic M? receptor stimulation...
  27. Dunn P, Benton D, Campos Rosa J, Ganellin C, Jenkinson D. Discrimination between subtypes of apamin-sensitive Ca(2+)-activated K+ channels by gallamine and a novel bis-quaternary quinolinium cyclophane, UCL 1530. Br J Pharmacol. 1996;117:35-42 pubmed
    ..UCL 1530 and gallamine should be useful tools for the investigation of subtypes of apamin-sensitive K+ channels...
  28. Poulsen H, Hougs W. The effect of some curarizing drugs in unanaesthetized man. I. d-Tubocurarine chloride, gallamonium iodide, decamethonium iodide, succinylcholine iodide and its bis-monoethyl-substituted derivative in single or repeated doses. Acta Anaesth. Scandinav. Acta Anaesthesiol Scand. 2007;51:1018-42; discussion 1043 pubmed
  29. Kunysz E, Michel A, Whiting R. Functional and direct binding studies using subtype selective muscarinic receptor antagonists. Br J Pharmacol. 1988;93:491-500 pubmed
    ..4. These data provide additional evidence, both from direct binding and functional studies, for the presence of M1 and M2 muscarinic receptor subtypes...
  30. Prilla S, Schrobang J, Ellis J, Höltje H, Mohr K. Allosteric interactions with muscarinic acetylcholine receptors: complex role of the conserved tryptophan M2422Trp in a critical cluster of amino acids for baseline affinity, subtype selectivity, and cooperativity. Mol Pharmacol. 2006;70:181-93 pubmed
    ..Thus, M2 422Trp and the spatially adjacent M2 177Tyr, as well as M2 423Thr, form a cluster of amino acids within the allosteric binding cleft that is pivotal for both M2/M5 subtype selectivity and baseline affinity of allosteric agents...
  31. Eichler J, Anselment A, Sussman J, Massoulie J, Silman I. Differential effects of "peripheral" site ligands on Torpedo and chicken acetylcholinesterase. Mol Pharmacol. 1994;45:335-40 pubmed
  32. Jakubik J, Tucek S. Protection by alcuronium of muscarinic receptors against chemical inactivation and location of the allosteric binding site for alcuronium. J Neurochem. 1994;63:1932-40 pubmed
  33. Moneret Vautrin D, Gueant J, Kamel L, Laxenaire M, el Kholty S, Nicolas J. Anaphylaxis to muscle relaxants: cross-sensitivity studied by radioimmunoassays compared to intradermal tests in 34 cases. J Allergy Clin Immunol. 1988;82:745-52 pubmed
  34. Krejci A, Tucek S. Changes of cooperativity between N-methylscopolamine and allosteric modulators alcuronium and gallamine induced by mutations of external loops of muscarinic M(3) receptors. Mol Pharmacol. 2001;60:761-7 pubmed
  35. Hinck D, Wulff H, Koppenhöfer E. Gallamine triethiodide selectively blocks voltage-gated potassium channels in Ranvier nodes. Gen Physiol Biophys. 2001;20:83-95 pubmed
    ..They also strongly suggest that potassium currents in Ranvier nodes of Xenopus are mainly carried by an ensemble of Kv1.1 and 1.2 channels...
  36. Anand B, Chhina G, Sharma K, Dua S, Singh B. ACTIVITY OF SINGLE NEURONS IN THE HYPOTHALAMIC FEEDING CENTERS: EFFECT OF GLUCOSE. Am J Physiol. 1964;207:1146-54 pubmed
  37. Lin J, Arthurs J, Reilly S. Reduced palatability in pain-induced conditioned taste aversions. Physiol Behav. 2013;119:79-85 pubmed publisher
    ..The current finding serves as evidence supporting the view that CTA is a broadly tuned mechanism that can be triggered by changes in internal body states following consummatory experience. ..
  38. Daval S, Kellenberger E, Bonnet D, Utard V, Galzi J, Ilien B. Exploration of the orthosteric/allosteric interface in human M1 muscarinic receptors by bitopic fluorescent ligands. Mol Pharmacol. 2013;84:71-85 pubmed publisher
    ..Altogether, this study illustrates the importance of a "multifacet" experimental approach to unravel and validate bitopic ligand binding mechanisms...
  39. Chen S, Huang Y, Kao Y, Chen G, Cheng C, Peng H, et al. Acute anal stretch inhibits NMDA-dependent pelvic-urethra reflex potentiation via spinal GABAergic inhibition in anesthetized rats. Am J Physiol Renal Physiol. 2008;295:F923-31 pubmed publisher
  40. Combes D, Fedon Y, Grauso M, Toutant J, Arpagaus M. Four genes encode acetylcholinesterases in the nematodes Caenorhabditis elegans and Caenorhabditis briggsae. cDNA sequences, genomic structures, mutations and in vivo expression. J Mol Biol. 2000;300:727-42 pubmed
    ..The molecular bases of null mutations g72 (ace-2), p1304 and dc2 (ace-3) have been identified...
  41. Proska J, Tucek S. Competition between positive and negative allosteric effectors on muscarinic receptors. Mol Pharmacol. 1995;48:696-702 pubmed
  42. Abbas M, Mostafa G. Gallamine-tetraphenylborate-modified carbon paste electrode for the potentiometric determination of gallamine triethiodide (flaxedil). J Pharm Biomed Anal. 2003;31:819-26 pubmed
    ..The construction and general performance of a novel modified carbon paste electrode for the determination of gallamine triethiodide have been developed...
  43. Guizzetti M, Bordi F, Dieguez Acuña F, Vitalone A, Madia F, Woods J, et al. Nuclear factor kappaB activation by muscarinic receptors in astroglial cells: effect of ethanol. Neuroscience. 2003;120:941-50 pubmed
  44. Filatov G, Aylwin M, White M. Selective enhancement of the interaction of curare with the nicotinic acetylcholine receptor. Mol Pharmacol. 1993;44:237-41 pubmed
  45. Sasongko L, Ramzan I, Williams K, McLachlan A. Application of a high-performance liquid chromatographic assay for the neuromuscular blocker gallamine to analysis of rat plasma, muscle and microdialysate samples. J Chromatogr B Biomed Sci Appl. 2001;754:467-75 pubmed
    ..6 microg/g for muscle tissue and 0.5 microg/ml for microdialysate samples. The assay was applied successfully to analysis of samples obtained from a pharmacokinetic study in rats using the microdialysis technique...
  46. Novi F, Scarselli M, Corsini G, Maggio R. An unusual form of the association binding kinetics of N-[3H]methylscopolamine to the split muscarinic M2trunk/M2tail receptor. J Pharmacol Exp Ther. 2003;305:786-95 pubmed
    ..We suggest that this peculiar form of the [(3)H]NMS association binding to the muscarinic M(2trunk)/M(2tail) receptor is attributable to a less stable interaction between the trunk and the tail fragments of the split receptor...
  47. Roffel A, Elzinga C, Zaagsma J. Cholinergic contraction of the guinea pig lung strip is mediated by muscarinic M2-like receptors. Eur J Pharmacol. 1993;250:267-79 pubmed
    ..It remains to be established, however, on what structure in the lung these contractile M2-like receptors are located and also by which transduction mechanism they produce contraction...
  48. Hernandez Echeagaray E, Galarraga E, Bargas J. 3-Alpha-chloro-imperialine, a potent blocker of cholinergic presynaptic modulation of glutamatergic afferents in the rat neostriatum. Neuropharmacology. 1998;37:1493-502 pubmed
    ..These data are consistent with the existence of both M2 and M3 muscarinic receptors in striatal glutamatergic afferents...
  49. Huwiler K, De Rosier T, Hanson B, Vogel K. A fluorescence anisotropy assay for the muscarinic M1 G-protein-coupled receptor. Assay Drug Dev Technol. 2010;8:356-66 pubmed publisher
    ..This M1 FA assay offers advantages over traditional radioligandbinding assays as it eliminates radioactivity while allowing investigation of orthosteric or allosteric muscarinic M1 ligands in a homogeneous format...
  50. Lanzafame A, Christopoulos A, Mitchelson F. Three allosteric modulators act at a common site, distinct from that of competitive antagonists, at muscarinic acetylcholine M2 receptors. J Pharmacol Exp Ther. 1997;282:278-85 pubmed
  51. Bilgen I, Oner G, Edremitlioglu M, Alkan Z, Cirrik S. Involvement of cholinoceptors in cadmium-induced endothelial dysfunction. J Basic Clin Physiol Pharmacol. 2003;14:55-76 pubmed
    ..These findings suggest that Cd produces an endothelial dysfunction by impairing the M1 type cholinoceptor mediated response, which seems to be involved in prostanoid release...
  52. Cembala T, Forde S, Appadu B, Lambert D. Allosteric interaction of the neuromuscular blockers vecuronium and pancuronium with recombinant human muscarinic M2 receptors. Eur J Pharmacol. 2007;569:37-40 pubmed
    ..36+/-0.03+blocker 0.03+/-0.01). These data indicate that vecuronium, gallamine and pancuronium interact with an allosteric site on the muscarinic M2 receptor (located on the heart) and this may explain some of their cardiac side effects...
  53. Cameron T, Richmond F, Loeb G. Effects of regional stimulation using a miniature stimulator implanted in feline posterior biceps femoris. IEEE Trans Biomed Eng. 1998;45:1036-43 pubmed