Combined blockade of α3β4 nicotinic acetylcholine receptors and GluR1 AMPA receptors in rats prevents kainate-induced tonic-clonic seizures

Serdyuk, S. E.; Гмиро, В. Е.

doi:10.1007/s10517-007-0195-7

Cited by 6 publications

(3 citation statements)

References 13 publications

(33 reference statements)

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“…2007), making this potential mechanism of action unlikely. The doses of IEM 1460 used in this study are similar to those found to have behavioural effects in a rat model of kainate‐induced epilepsy (Serdyuk and Gmiro 2007).…”

Section: Discussionmentioning

confidence: 55%

Calcium‐permeable AMPA receptors are involved in the induction and expression of l‐DOPA‐induced dyskinesia in Parkinson’s disease

Kobylecki

Cenci

Crossman

et al. 2010

Journal of Neurochemistry

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J. Neurochem. (2010) 114, 409–511. Abstract Overactivity of striatal α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) glutamate receptors is implicated in the pathophysiology of l‐DOPA‐induced dyskinesia (LID) in Parkinson’s disease (PD). In this study, we evaluated the behavioural and molecular effects of acute and chronic blockade of Ca2+‐permeable AMPA receptors in animal models of PD and LID. The acute effects of the Ca2+‐permeable AMPA receptor antagonist 1‐trimethylammonio‐5‐(1‐adamantane‐methylammoniopentane) dibromide hydrobromide (IEM 1460) on abnormal involuntary movements (AIMs) in the 6‐hydroxydopamine (6‐OHDA)‐lesioned rat and LID in the MPTP‐lesioned non‐human primate were assessed. Subsequently, the effects of chronic treatment of 6‐OHDA‐lesioned rats with vehicle, l‐DOPA/benserazide (6/15 mg/kg, i.p.) + vehicle or l‐DOPA + IEM 1460 (3 mg/kg, i.p.) on behavioural and molecular correlates of priming for LID were evaluated. In the 6‐OHDA‐lesioned rat and MPTP‐lesioned non‐human primate, acute treatment with IEM 1460 (1–3 mg/kg) dose‐dependently reduced LID without adverse effects on motor performance. Chronic co‐treatment for 21 days with IEM 1460 reduced the induction of AIMs by l‐DOPA in the 6‐OHDA‐lesioned rat without affecting peak rotarod performance, and attenuated AIMs score by 75% following l‐DOPA challenge (p < 0.05). Chronic IEM 1460 treatment reversed l‐DOPA‐induced up‐regulation of pre‐proenkephalin‐A, and normalised pre‐proenkephalin‐B mRNA expression in the lateral striatum, indicating an inhibition of both behavioural and molecular correlates of priming. These data suggest that Ca2+‐permeable AMPA receptors are critically involved in both the induction and subsequent expression of LID, and represent a potential target for anti‐dyskinetic therapies.

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Section: Discussionmentioning

confidence: 55%

Calcium‐permeable AMPA receptors are involved in the induction and expression of l‐DOPA‐induced dyskinesia in Parkinson’s disease

Kobylecki

Cenci

Crossman

et al. 2010

Journal of Neurochemistry

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“…ИЭМ-1460, блокирующий, подобно спермину, только GluA1 AMPA-рецепторы, имеет принципиальное преимущество перед известными неизбирательными AMPAблокаторами. В отличие от спермина ИЭМ-1460 вызывает полный блок GluA1 AMPA рецепторов и обладает высокой нейропротекторной активностью [137][138][139][140][141][142][143][144][145][146].…”

Section: иэм-1460 как избирательный Glua1 Ampa блокаторunclassified

“…Подобное сочетание свойств в одном препарате должно было бы придать ему высокую эффективность и на других фармакологических тестах, что и подтвердилось на практике. ИЭМ-1460 существенно улучшает когнитивную функцию [159], устраняет дискинезию, вызванную леводопой [142,143], а также МК-и фенциклидин-вызванную токсичность на соответствующих моделях шизофрении [141], предложен для лечения воспалительной боли, гипералгезии, диабетической невропатической боли [144,145,161], эпилепсии [137,138,140,146,156,162], аддикции [163], для предотвращения вызванной шумом улитковой синаптопатии [164].…”

Section: иэм-1460 -позитивный модулятор Ampa-рецепторов пирамид содер...unclassified

Selective antagonists of calcium-permeable GluA1 AMPA-receptors as potential antiaddictive agents

Potapkin

Гмиро

Shabanov

2023

Psychopharmacology & biological narcology

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An increase in synaptic dopamine levels, particularly in the nucleus accumbens sheath, is a critical initial response for encoding a drugs positive effect and the development of associative learning, which is crucial for finding drugs in response to their rewarding effects. This study aims to review current data describing the role of AMPA glutamate receptors in the pathological drug search that occurs during the transition from drug use to drug abuse. Publications reviewed and analyzed the journal publications in international databases (PubMed, Web of Science, Scopus, RSCI) on the mechanisms of interaction between dopamine and AMPA glutamate receptors in drug addiction pathogenesis are reviewed and analyzed. After repeated exposure to psychostimulant drugs, the dopamine response to narcogen administration becomes sensitized, which is responsible for drugs of abuse over other natural reinforcers. The nucleus accumbens contains convergent inputs of dopamine and glutamate, which modulate the response to psychostimulant drugs. Simultaneously, a constant increase in AMPA-receptors lacking the GluA2 subunit was observed, which leads to an increase in conductivity and initiates a cascade of calcium-dependent signaling. With the development of compulsive drug seeking, the expression of AMPA-receptors in the nucleus accumbens increases. Based on this hypothesis, it is reasonable to propose drugs for the treatment of drug dependence that counteract the neuroplastic changes in AMPA-receptors caused by repeated drug exposure and leading to addiction. IEM-1460 and IEM-2131, which are two GluA1 AMPA blockers, have been proposed as potential therapeutic agents against addiction and other CNS diseases.

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Peripheral and central routes of administration of quaternary ammonium compound IEM-1460 are equally potent in reducing the severity of nicotine-induced seizures in mice

2008

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Peripheral administration of nicotinic receptor antagonists with a quaternary ammonium group (hexamethonium and chlorisondamine) did not prevent the development of seizures induced by systemic treatment with nicotine in the toxic dose. The Me3N+ group with stable positive charge inhibits transport of these compounds into the brain through the blood-brain barrier. Intracerebral and peripheral (intraperitoneal) administration of compound IEM-1460 with the Me3N+ group was equally potent in reducing the severity of nicotine-induced seizures in mice. This phenomenon is related to the fact that IEM-1460 acts as a nicotinic receptor antagonist and polyamine agonist, which increases blood-brain barrier permeability for polar compounds. These features contribute to IEM-1460 transport into the brain. High anticonvulsant activity of IEM-1460 on the model of nicotine-induced seizures is associated with combined blockade of nicotinic receptors (alpha3beta4 receptors) and glutamate receptors (GluR1 AMPA receptors).

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Combined blockade of α3β4 nicotinic acetylcholine receptors and GluR1 AMPA receptors in rats prevents kainate-induced tonic-clonic seizures

Cited by 6 publications

References 13 publications

Calcium‐permeable AMPA receptors are involved in the induction and expression of l‐DOPA‐induced dyskinesia in Parkinson’s disease

Calcium‐permeable AMPA receptors are involved in the induction and expression of l‐DOPA‐induced dyskinesia in Parkinson’s disease

Selective antagonists of calcium-permeable GluA1 AMPA-receptors as potential antiaddictive agents

Peripheral and central routes of administration of quaternary ammonium compound IEM-1460 are equally potent in reducing the severity of nicotine-induced seizures in mice

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