Effects of ionotropic glutamate receptor channel blockers on the development of pentylenetetrazol kindling in mice

被引：8

作者：

Lukomskaya N.Ya. ^{[1
]}

Lavrent'eva V.V. ^{[1
]}

Starshinova L.A. ^{[1
]}

Zhabko E.P. ^{[1
]}

Gorbunova L.V. ^{[1
]}

Tikhonova T.B. ^{[1
]}

Gmiro V.E. ^{[2
]}

Magazanik L.G. ^{[1
]}

机构：

[1] I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 194223 St. Petersburg

[2] Institute of Experimental Medicine, Russian Academy of Medical Sciences, 197376 St. Petersburg

来源：

Neuroscience and Behavioral Physiology | 2007年 / 37卷 / 1期

基金：

俄罗斯基础研究基金会;

关键词：

AMPA receptors; Channel blockers; Kindling; Mice; NMDA receptors; Pentylenetetrazol;

D O I：

10.1007/s11055-007-0152-y

中图分类号：

学科分类号：

摘要：

Experiments on mice were performed to study the ability of monocationic and dicationic adamantane and phenylcyclohexyl derivatives to prevent the development of kindling induced by i.p. administration of pentylenetetrazol (Corasol, 35 mg/kg). The monocationic phenylcyclohexyl derivative IEM-1921 effectively slowed the development of kindling, this being seen over a wide range of doses (0.0001-0.1 μmol/kg). A monocationic adamantane derivative (memantine), also a selective non-competitive blocker of NMDA receptors, produced a similar effect at doses 100 times higher. The anticonvulsive activity of the dicationic phenylcyclohexyl derivative IEM-1925, which could block both types of glutamate receptors, differed from the activity of the monocationic derivative by having a more complex dose-response relationship. Thus, the development of kindling was suppressed by essentially the same doses as needed for the monocation IEM-1921 (0.001 μmol/kg). However, on reducing the dose by a factor of 10 (0.0001 μmol/kg), IEM-1925 facilitated the development of kindling. This difference in the prophylactic activities of selective NMDA receptor blockers and substances able to block both NMDA and AMPA receptors provides evidence that the mechanism of kindling involves both types of ionotropic glutamate receptor and the effects of compounds depend not only on the ratio of the contributions of these receptors, but also on the kinetic characteristics of the blocking action. © Springer Science+Business Media, Inc. 2007.

引用

页码：75 / 81

页数：6

共 33 条

[1]

Lukomskaya N.Ya., Rukoyatkina N.I., Gorbunova L.V., Gmiro V.E., Bol'shakov K.V., Magazanik L.G., Comparison of the anti-convulsive activities of organic mono-and dications with their abilities to inhibit NMDA and AMPA glutamate receptors, Ros. Fiziol. Zh. Im. I. M. Sechenova, 88, pp. 1161-1171, (2002)

[2]

Lukomskaya N.Ya., Rukoyatkina N.I., Gorbunova L.V., Gmiro V.E., Magazanik L.G., Studies of the roles of NMDA and AMPA glutamate receptors in the mechanism of Corasol convulsions in mice, Ros. Fiziol. Zh. Im. I. M. Sechenova, 89, 3, pp. 292-301, (2003)

[3]

Magazanik L.G., Bol'shakov K.V., Buldakova S.L., Gmiro V.E., Dorofeeva N.A., Lukomskaya N.Ya., Potap'eva N.N., Samoilov M.V., Tikhonov D.B., Fedorova I.M., Frolova E.V., Structural characteristics of ionotropic glutamate receptors detected by channel blockade, Ros. Fiziol. Zh. Im. I. M. Sechenova, 86, 9, pp. 1138-1151, (2000)

[4]

Rukoyatkina N.I., Gorbunova L.V., Gmiro V.E., Lukomskaya N.Ya., The ability of a number of non-competitive glutamate receptor blockers to ameliorate motor disorders in animals, Ros. Fiziol. Zh. Im. I. M. Sechenova, 87, 9, pp. 1260-1267, (2001)

[5]

Tikhonova T.B., Tikhonov D.B., Magazanik L.G., Characteristics of blockade of the ion channels of glutamate channels of the NMDA and AMPA subtypes by dicationic derivatives of phenylcyclohexyl, Biol. Membrany, 22, 4, pp. 311-320, (2005)

[6]

Becker A., Greksch G., Schroder H., Low doses of AMPA exert anticonvulsant effects on pentylenetetrazol-kindled seizures, Pharmacol. Biochem. Behav., 70, pp. 421-426, (2001)

[7]

Bengzon J., Okabe S., Lindvall O., McKay R.D., Suppression of epileptogenesis by modification of N-methyl-D-aspartate receptor subunit composition, Eur. J. Neurosci., 11, pp. 916-922, (1999)

[8]

Bolshakov K.V., Tikhonov D.B., Gmiro V.E., Magazanik L.G., Different arrangements of hydrophobic and nucleophilic components of channel binding sites in N-methyl-D-aspartate and AMPA receptors of rat brain is revealed by channel blockade, Neurosci. Lett., 291, pp. 101-104, (2000)

[9]

Bolshakov K.V., Gmiro V.E., Tikhonov D.B., Magazanik L.G., Determinants of trapping block of N-methyl-D-aspartate receptor channels, J. Neurochem., 87, pp. 56-65, (2003)

[10]

Bolshakov K.V., Kim K.H., Potapjeva N.N., Gmiro V.E., Tikhonov D.B., Usherwood P.N.R., Mellor I.R., Magazanik L.G., Design of antagonists for NMDA and AMPA receptors, Neuropharmacology, (2005)

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