Cleft-type cyclophanes confer neuroprotection against excitatory neurotoxicity in vitro and in vivo through inhibition of NMDA receptors

Masuko, Takashi; Nemoto, Yuta; Nagaoka, Hiroki; Miyake, Muneharu; Kizawa, Yasuo; Kusama-Eguchi, Kuniko; Kashiwagi, Keiko; Igarashi, Kazuei; Kusama, Tadashi

doi:10.1016/j.neuropharm.2007.06.013

Cited by 6 publications

(8 citation statements)

References 29 publications

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“…The IC 50 values for ketamine and memantine are 1.4 and 1.0 mM respectively against NMDA receptors expressed in Xenopus oocyte using voltage-clamp recording. 4,8) The degree of inhibition by ACPCm (1) (IC 50 , 1.06 mM) and ACPCn (2) (IC 50 …”

Section: Resultsmentioning

confidence: 99%

“…Adult female Xenopus laevis were chilled on ice, and the preparation and maintenance of oocytes were performed as described previously. 4,10) Capped cRNAs were prepared from linearized cDNA templates using mMessage mMachine kits (Ambion, Austin, TX, U.S.A.). Oocytes were injected with NR1A and NR2 cRNAs at a ratio of 1 : 5 (0.2-4 ng of NR1A plus 1-20 ng of NR2).…”

Section: Methodsmentioning

confidence: 99%

“…This solution contained BaCl 2 rather than CaCl 2 , and, in most experiments, oocytes were injected with K ϩ -1,2-bis(2-aminophenoxy)ethane-N,N,NЈ,NЈ-tetraacetic acid (BAPTA; 100 nl of 40 mM solution at pH 7.5) on the day of recording to eliminate Ca 2ϩ -activated Cl Ϫ currents. 4,9) Glutamate and glycine were purchased from Wako Pure Chemical Industries, Ltd. (Osaka, Japan). BAPTA were purchased from Sigma (St. Louis, MO, U.S.A.).…”

Section: Methodsmentioning

confidence: 99%

“…1) We previously reported the synthesis of two cleft-type cyclophanes ACCn 3,4) and ATGDMAP 5) which inhibited the activity of the NR1/NR2A and NR1/NR2B receptors at Ϫ70 mV. The IC 50 values for ACCn and ATGDMAP were 7.0 and 4.9 mM respectively against the NMDA receptors.…”

Section: Notesmentioning

confidence: 97%

“…The inhibition of the activity of the NR1/NR2A and NR1/NR2B receptors by N-(2-{4- [4-(2-{[(1,4,7,10- (1,4,7,10- [2-(toluene-4-sulfonylamino)ethyl]acetamide (TsDCn), both of which have two sulfonamide groups, was stronger than that of ACCn. 4) In the present study, we attempted to synthesize more potent cleft-type cyclophanes than ACCn and ATGDMAP (Fig. 1).…”

Section: Notesmentioning

confidence: 99%

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Synthesis of a Novel Water-Soluble Cleft-Type Cyclophane as an N-Methyl-D-aspartate Receptor Antagonist

Masuko

Kusama

Namiki

et al. 2009

CHEMICAL & PHARMACEUTICAL BULLETIN

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NotesThe ionotropic glutamate receptors are ligand-gated ion channels that mediate the vast majority of excitatory neurotransmission in the brain. The three pharmacologically defined classes of ionotropic glutamate receptor were originally named after the reasonably selective agonists N-methyl-D-aspartate (NMDA), a-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), and kainite. It turned out that NMDA, AMPA, and kainite receptor subunits are encoded by at least six gene families as defined by sequence homology: a single family for the AMPA receptors, two for kainite, and three for NMDA.1) The NMDA receptor combines to form heteromeric complexes containing NR1 and NR2 subunits. The NR1 subunit is ubiquitous and assembles with a second family of subunits termed NR2, including NR2A, NR2B, NR2C and NR2D.In the central nervous system (CNS), the NMDA receptor plays a critically important role in a variety of neurophysiological phenomena, including neuronal development, synaptic plasticity, and excitotoxicity. Glutamate is known to be neurotoxic under certain circumstances, in particular when energy supply is compromised. Thus some researchers now believe that the neurodegeneration associated with a variety of acute and chronic disorders (ischemic stroke, Parkinson's disease, Alzheimer's disease, dementia, etc.) may be caused in part by overactivation of glutamate receptors. Alzheimer's disease is a neurodegenerative disorder characterized by irreversible, progressive loss of memory followed by complete dementia. The cognitive decline is accompanied by impaired performance of daily activities, behavior, speech and visualspatial perception. Glutamate excitotoxicity as a result of blockade of glutamate uptake into astrocytes by Ab aggregates induces excessive Ca influx through mainly the NMDA receptors, followed by neuronal cell death.2) The NMDA receptor subtype has been found to play a key role in glutamate promotion of synaptic plasticity, long-term potentiation and neuronal cell death. 1)We previously reported the synthesis of two cleft-type cyclophanes ACCn 3,4) and ATGDMAP 5) which inhibited the activity of the NR1/NR2A and NR1/NR2B receptors at Ϫ70 mV. The IC 50 values for ACCn and ATGDMAP were 7.0 and 4.9 mM respectively against the NMDA receptors. The inhibition of the activity of the NR1/NR2A and NR1/NR2B receptors by N- (2-{4-[4-(2-{[(1,4,7,10- N-methyl-D-aspartate (NMDA) receptor antagonists, 4,4-bis({2-[N-(1,4,8,11-tetraazacyclotetradecan-1-yl)acetyl]-N-phenethyl}aminoethoxy)diphenylmethane octahydrochloride (1, ACPCm) and 4,4-bis({2-[N-(1,4,7,10-tetraazacyclododecan-1-yl)acetyl]-N-phenethyl}aminoethoxy)diphenylmethane octahydrochloride (2, ACPCn), were synthesized and the effect of these cleft-type cyclophanes on NMDA receptors was then studied using voltage-clamp recordings of recombinant NMDA receptors expressed in Xenopus oocytes. ACPCm (1) and ACPCn (2) inhibited macroscopic currents in the NR1/NR2A, NR1/NR2B, NR1/NR2C and NR1/NR2D receptor subtypes in oocytes voltage-clamped at ؊70 mV. The IC 50 ...

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Notesmentioning

confidence: 97%

Section: Notesmentioning

confidence: 99%

See 3 more Smart Citations

Synthesis of a Novel Water-Soluble Cleft-Type Cyclophane as an N-Methyl-D-aspartate Receptor Antagonist

Masuko

Kusama

Namiki

et al. 2009

CHEMICAL & PHARMACEUTICAL BULLETIN

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Animal models of neonatal stroke and response to erythropoietin and cardiotrophin‐1

Sola

Peng

Rogido

et al. 2007

Intl J of Devlp Neuroscience

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Neonatal stroke is increasingly recognized in preterm and term infants, and the rate of arterial ischemic infarction occurring around the time of birth is as high as the annual incidence of large-vessel ischemic stroke in adults. Thus, neonatal stroke is a major contributor to perinatal morbidity and mortality, and a considerable number of these children will develop long-term neurodevelopmental disabilities. Our ability to investigate this situation has been limited by the technical challenges in developing suitable animal models. Our objective is to describe recent evidence in relation to animal models of neonatal stroke. In addition, we review and report potential neuroprotective strategies specific to neonatal stroke, with a focus on erythropoietin and cardiotrophin-1 because of their potential role in protection as well as repair.

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Differential effects of linear and cyclic polyamines on NMDA receptor activities

Masuko¹,

Miyake²,

Kusama-Eguchi³

et al. 2008

Neurochemistry International

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Cleft-type cyclophanes confer neuroprotection against excitatory neurotoxicity in vitro and in vivo through inhibition of NMDA receptors

Cited by 6 publications

References 29 publications

Synthesis of a Novel Water-Soluble Cleft-Type Cyclophane as an N-Methyl-D-aspartate Receptor Antagonist

Synthesis of a Novel Water-Soluble Cleft-Type Cyclophane as an N-Methyl-D-aspartate Receptor Antagonist

Animal models of neonatal stroke and response to erythropoietin and cardiotrophin‐1

Differential effects of linear and cyclic polyamines on NMDA receptor activities

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