Abstract
Administration of the muscarinic cholinoreceptor agonist arecoline (6 mg/kg, s.c.) to mice induced long-lasting tremor. The ability of non-competitive antagonists of ionotropic glutamate receptors to suppress the onset of tremor was studied. These antagonists, i.e., adamantane and phenylcyclohexyl derivatives, selectively blocked NMDA-type receptor channels (monocations) or both NMDA-and AMPA-type channels (dications). Both types of blocker weakened arecoline tremor, though the dose-response relationships were different for mono-and dications. The effects of dications appeared only at low blocker doses (0.0001–0.01 µmol/kg) but gradually disappeared on dose elevation. These data lead to the conclusion that the mechanism of pathogenesis of arecoline tremor predominantly involves NMDA-type receptors. Moderate blockade of AMPA-type receptors could potentiate the preventive effect of mixed-action antagonists (anti-NMDA + anti-AMPA), though predominance of blocking action against AMPA-type receptors prevented this effect.
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E. A. Val’dman, T. A. Voronina, and L. N. Nerobokova, “Antiparkinson activity of a new adamantane derivative,” Éksperim. Klin. Farmacol., 62, No. 4, 3–6 (1999).
N. Ya. Lukomskaya, E. P. Zhabko, and V. E. Gmiro, “Involvement of glutamatergic transmission in the mechanism of motor lesions evoked by reversive rotation,” Ros. Fiziol. Zh. im. I. M. Sechenova, 85, No. 4, 497–501 (1999).
N. Ya. Lukomskaya, N. I. Rukoyatkina, L. V. Gorbunova, V. E. Gmiro, K. V. Bol’shakov, and L. G. Magazanik, “Comparison of the anticonvulsive activity of organic mono-and dications with their ability to inhibit NMDA and AMPA glutamate receptors,” Ros. Fiziol. Zh. im. I. M. Sechenova, 88, 1161–1171 (2002).
N. Ya. Lukomskaya, N. T. Rukoyatkina, L. V. Gorbunova, V. E. Gmiro, and L. G. Magazanik, “Studies of the role of NMDA and AMPA glutamate receptors in the mechanism of convulsive syndrome evoked by corasol in mice,” Ros. Fiziol. Zh. im. I. M. Sechenova, 89, No. 3, 292–301 (2003).
N. Ya. Lukomskaya, V. V. Lavrent’eva, L. A. Starshinova, E. P. Zhabko, L. V. Gorbunova, T. B. Tikhonova, V. E. Gmiro, and L. G. Magazanik, “Effects of blockers of the channels of ionotropic glutamate receptors on the development of pentylenetetrazole kindling in mice,” Ros. Fiziol. Zh. im. I. M. Sechenova, 91, No. 11, 1241–1250 (2005).
L. G. Magazanik, N. Ya. Lukomskaya, N. I. Rukoyatkina, L. V. Gorbunova, V. E. Gmiro, and K. V. Bol’shakov, “Comparison of the anticonvulsive activity of organic mono-and dications with their ability to inhibit NMDA and AMPA glutamate receptors,” Ros. Fiziol. Zh. im. I. M. Sechenova, 88, No. 9, 1161–1171 (2002).
L. G. Magazanik, D. B. Tikhonov, T. B. Tikhonova, and N. Ya. Lukomskaya, “Mechanisms of blockade of glutamate receptor channels: significance for structural and physiological investigations,” Ros. Fiziol. Zh. im. I. M. Sechenova, 92, No. 1, 27–38 (2006).
N. I. Rukoyatkina, L. V. Gorbunova, V. E. Gmiro, and N. Ya. Lukomskaya, “The ability of glutamate receptor antagonists to weaken experimental catalepsy in rats,” Ros. Fiziol. Zh. im. I. M. Sechenova, 86, No. 6, 626–634 (2000).
N. I. Rukoyatkina, L. V. Gorbunova, V. E. Gmiro, and N. Ya. Lukomskaya, “The ability of new non-competitive glutamate receptor blockers to weaken motor disorders in animals,” Ros. Fiziol. Zh. im. I. M. Sechenova, 87, No. 9, 1260–1267 (2001).
S. A. Chepurnov, N. E. Chepurnova, O. M. Redkozubova, and S. A. Saakyan, “Status epilepticus — new mechanisms and pathways of inhibition (a lithium-pilocarpine model),” Usp. Fiziol. Nauk., 36, No. 1, 68–84 (2005).
A. Ahmadiani, A. Mandgary, and M. Sayyah, “Anticonvulsant effect of flutamide on seizures induced by pentylenetetrazole: involvement of benzodiazepine receptors,” Epilepsia, 44, No. 5, 629–635 (2003).
K. V. Bolshakov, V. E. Gmiro, D. B. Tikhonov, and L. G. Magazanik, “Determinants of trapping block of N-methyl-d-aspartate receptor channels,” J. Neurochem., 87, No. 1, 56–65 (2003).
K. V. Bolshakov, K. H. Kim, N. N. Potapjeva, V. E. Gmiro, D. B. Tikhonov, P. N. Usherwood, I. R. Mellor, and L. G. Magazanik, “Design of antagonists for NMDA and AMPA receptors,” Neuropharmacology, 49, 144–155 (2005).
N. O. Dalby, “GABA-level increasing and anticonvulsant effects of three different GABA uptake inhibitors,” Neuropharmacol., 39, No. 12, 2399–2407 (2000).
K. Dingledine, K. Borges, D. Bowie, and S. F. Traynelis, “The glutamate receptor ion channels,” Pharmacol. Rev., 51, 7–61 (1999).
A. Foster and J. A. Kemp, “Glutamate-and GABA-based CN therapeutics,” Curr. Opin. Pharmacol., 6, No. 1, 7–17 (2006).
D. G. Fujikawa, A. H. Daniels, and J. S. Kim, “The competitive NMDA receptor antagonist CGP 40116 protects against status epilepticus-induced neuronal damage,” Epilepsy Res., 17, 207–219 (1994).
W. Loscher, “New vision in the pharmacology of anticonvulsion,” Eur. J. Pharmacol., 342, 1–13 (1998).
W. Loscher, “Current status and future directions in the pharmacotherapy of epilepsy,” Trends Pharmacol. Sci., 23, No. 3, 113–118 (2002).
W. Loscher and D. Schmidt, “Which animal models should be used in the search for new antiepileptic drugs? A proposal based on experimental and clinical considerations,” Epilepsy Res., 2, 145–181 (1988).
L. G. Magazanik, S. L. Buldakova, M. V. Samoilova, V. E. Gmiro, I. R. Mellor, and P. N. R. Usherwood, “Block of open channels of recombinant AMPA receptors and native AMPA/kainate receptors by adamantane derivates,” J. Physiol. (London), 505, 655–663 (1997).
R. A. Morrisett, R. S. Jope, and O. C. Snead III, “Effects of drugs on the initiation and maintenance of status epilepticus induced by administration of pilocarpine to lithium-pretreated rats,” Exptl. Neurol., 97, 193–200 (1987).
M. E. Nevins and S. M. Arnolde, “A comparison of the anticonvulsant effects of competitive and non-competitive antagonists of the NMDA receptor,” Brain Res., 503, No. 1, 1–4 (1989).
C. G. Parsons, W. Danysz, and G. Quack, “Glutamate in CNS disorders as a target for drug development: an update,” Drug New Perspect., 11, 523–569 (1998).
M. A. Rogawski and R. J. Porter, “Antiepileptic drugs: Pharmacological mechanisms and clinical efficacy with consideration of promising developmental stage compounds,” Pharmacol. Rev., 42, No. 3, 223–286 (1990).
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Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 93, No. 3, pp. 275–282, March, 2007.
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Lukomskaya, N.Y., Lavrent’eva, V.V., Starshinova, L.A. et al. Involvement of ionotropic glutamate receptors in the appearance of arecoline tremor in mice. Neurosci Behav Physi 38, 421–426 (2008). https://doi.org/10.1007/s11055-008-0060-9
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DOI: https://doi.org/10.1007/s11055-008-0060-9