The NR2B antagonist, ifenprodil, corrects the l-DOPA-induced deficit of bilateral movement and reduces c-Fos expression in the subthalamic nucleus of hemiparkinsonian rats

Igarashi, Masakazu; Habata, Toshiya; Akita, Hisanao; Noda, Katsuji; Ogata, Masao; Saji, Makoto

doi:10.1016/j.neures.2015.02.003

Cited by 9 publications

(5 citation statements)

References 48 publications

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“…This suggests that therapy targeting NR2B-containing receptors can contribute to more specific effects influencing the NMDA receptor regulation in brain regions related to PD pathophysiology. This was determined by Ifenprodil and traxoprodil (CP-101, 606), antagonists of the NR2B subunit-containing NMDA receptor, which were shown to ameliorate Parkinsonian symptoms and reduce LID in rodents and MPTP-lesioned monkeys [72,73]. The combination therapy of NR2B-selective antagonists with other drugs was also applied.…”

Section: Key Targets Of Glutamate Receptors In Pd Treatmentmentioning

confidence: 99%

Roles of Glutamate Receptors in Parkinson’s Disease

Zhang

et al. 2019

IJMS

108

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Parkinson’s disease is a progressive neurodegenerative disorder resulting from the degeneration of pigmented dopaminergic neurons in the substantia nigra pars compacta. It induces a series of functional modifications in the circuitry of the basal ganglia nuclei and leads to severe motor disturbances. The amino acid glutamate, as an excitatory neurotransmitter, plays a key role in the disruption of normal basal ganglia function regulated through the interaction with its receptor proteins. It has been proven that glutamate receptors participate in the modulation of neuronal excitability, transmitter release, and long-term synaptic plasticity, in addition to being related to the altered neurotransmission in Parkinson’s disease. Therefore, they are considered new targets for improving the therapeutic strategies used to treat Parkinson’s disease. In this review, we discuss the biological characteristics of these receptors and demonstrate the receptor-mediated neuroprotection in Parkinson’s disease. Pharmacological manipulation of these receptors during anti-Parkinsonian processes in both experimental studies and clinical trials are also summarized.

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Section: Key Targets Of Glutamate Receptors In Pd Treatmentmentioning

confidence: 99%

Roles of Glutamate Receptors in Parkinson’s Disease

Zhang

et al. 2019

IJMS

108

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“…Parkinsonian patients have difficulty in asymmetric bimanual coordination (Almeida et al 2002;Ponsen et al 2006;Stelmach and Worringham 1988). Recent evidence suggests that recovery from hypokinesia in Parkinson's disease is not necessarily correlated with improvement in coordinated bimanual movements (Almeida and Brown 2013;Daneault et al 2016;Igarashi et al 2015). The decline in bimanual motor performance is also seen in healthy aging (Serbruyns et al 2015).…”

Section: Discussionmentioning

confidence: 99%

Kinematic analysis of bimanual movements during food handling by head-fixed rats

Igarashi

Wickens

2019

Journal of Neurophysiology

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Bimanual coordination, in which both hands work together to achieve a goal, is crucial for the basic needs of life, such as gathering and feeding. Such coordinated motor skill is highly developed in primates, where it has been most extensively studied. Rodents also exhibit remarkable dexterity and coordination of forelimbs during food handling and consumption. However, rodents have been less commonly used in the study of bimanual coordination because of limited quantitative measuring techniques. In this article we describe a high-resolution tracking system that enables kinematic analysis of rat forelimb movement. The system is used to quantify forelimb movements bilaterally in head-fixed rats during food handling and consumption. Forelimb movements occurring naturally during feeding were encoded as continuous three-dimensional trajectories. The trajectories were then automatically segmented and analyzed, using a novel algorithm, according to the laterality of movement speed or the asymmetry of movement direction across the forelimbs. Bilateral forelimb movements were frequently observed during spontaneous food handling. Both symmetry and asymmetry in movement direction were frequently observed, with symmetric bilateral movements quantitatively more common. The proposed method overcomes a limitation in the precise quantification of bimanual coordination in rodents. This enables the use of powerful rodent-based research tools such as optogenetics and chemogenetics in the further investigation of neural mechanisms of bimanual coordination. NEW & NOTEWORTHY We describe a new method for quantifying and classifying three-dimensional, bilateral forelimb trajectories in head-fixed rats. The method overcomes limits on quantifying bimanual coordination in rats. When applied to kinematic analysis of food handling behavior, continuous forelimb trajectories were automatically segmented and classified. Bilateral forelimb movements were observed more frequently than unilateral movements during spontaneous food handling. Both symmetry and asymmetry in movement direction were frequently observed. However, symmetric bilateral forelimb movements were more common.

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“…When given intrathecally for seven days, ifenprodil prominently inhibited the NR2B subunit expression in the spinal cord region of a painful diabetic neuropathy rat model, thus alleviating the tactile allodynia and formalininduced pain responses. Furthermore, in the preclinical phase of another two studies, this drug was found to act synergistically with levodopa (L-DOPA), tricyclic antidepressants and selective serotonin reuptake inhibitors used to treat depression in Parkinson's disease (73,74). There is also evidence to suggest that CP-101, 606, a compound of ifenprodil (also known as the α 1adrenoceptor antagonist and selective NR2B subunit antagonist) can inhibit the activation of NR2B subunit via interaction on the polyamine modulatory site (75).…”

Section: Direct Inhibition Of Nr2b Subunit Of Nmdar May Alleviate Ra mentioning

confidence: 99%

A Review on Chronic Pain in Rheumatoid Arthritis: A Focus on Activation of NR2B Subunit of N-Methyl-D-Aspartate Receptors

Noh

Ismail

2020

MJMS

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Chronic pain is a debilitating condition that occurs after tissue damage, which substantially affects the patient's emotional state and physical activity. The chronic pain in rheumatoid arthritis (RA) is the result of various autoimmune-induced inflammatory reactions in the joints. Both types of peripheral and central pain processing can lead to sensitisation. Non-steroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs (DMARDs) can result in potent anti-inflammatory effect. However, these drugs are not able to suppress the pain from RA for a prolonged period. For years, researchers have examined the role of the N-methyl-D-aspartic acid receptor 2B (NR2B) subunit of N-methyl-D-aspartate receptors (NMDAR) in chronic and neuropathic pain models. This NMDAR subtype can be found in at the peripheral and central nervous system and it represents an effective therapy for RA pain management. This review focuses on the NR2B subunit of NMDAR and the different pathways leading to its activation. Furthermore, specific attention is given to the possible involvement of NR2B subunit in the peripheral and central pathogenesis of RA.

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The NR2B antagonist, ifenprodil, corrects the l-DOPA-induced deficit of bilateral movement and reduces c-Fos expression in the subthalamic nucleus of hemiparkinsonian rats

Cited by 9 publications

References 48 publications

Roles of Glutamate Receptors in Parkinson’s Disease

Roles of Glutamate Receptors in Parkinson’s Disease

Kinematic analysis of bimanual movements during food handling by head-fixed rats

A Review on Chronic Pain in Rheumatoid Arthritis: A Focus on Activation of NR2B Subunit of N-Methyl-D-Aspartate Receptors

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