Anti-allodynic interactions between NMDA receptor channel blockers and morphine or clonidine in neuropathic rats

Malyshkin, A.; Medvedev, Ivan O.; Danysz, Wojciech; Bespalov, Anton

doi:10.1016/j.ejphar.2005.07.003

Cited by 12 publications

(9 citation statements)

References 27 publications

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“…Many authors have demonstrated that MK-801 reverse diabetes-induced thermal hyperalgesia (Malcangio and Tomlinson, 1998; Begon et al, 2000; Gupta et al, 2003; Karadag et al, 2003; Daulhac et al, 2006). Additionally, a combination of NMDA receptor antagonists with opioids has been shown to be efficient in the treatment of diabetic neuropathic pain (Begon et al, 2002; Bujalska et al, 2008) and other forms of neuropathic pain (Nichols et al, 1997; Malyshkin et al, 2005). It has been well defined that acupuncture induces general analgesic effects in experimental studies, and the participation of various endogenous opioids and their receptors has been widely accepted (Han, 2004; Okada and Kawakita, 2009).…”

Section: Discussionmentioning

confidence: 99%

Antiallodynic Effects of Electroacupuncture Combined with MK-801 Treatment through the Regulation of p35/p25 in Experimental Diabetic Neuropathy

et al. 2011

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The anti-allodynic effect of NMDA receptor antagonist and acupuncture treatments were explored through spinal p35 regulation of diabetic neuropathic rat. We evaluated the change over time of p35/p25 protein levels in the spinal cord compared with behavioral responses to thermal and mechanical stimulation in streptozotocin (STZ)-induced diabetic rats. Additionally, we studied p35 expression when electroacupuncture (EA) and a sub-effective dose of NMDA (N-methyl-D-aspartate) receptor antagonist (MK-801) were used to treat hyperalgesia in the diabetic neuropathic pain (DNP). Thermal paw withdrawal latency (PWL) and mechanical paw withdrawal threshold (PWT) were significantly decreased in the early stage of diabetes in rats. p35 expression after STZ injection gradually decreased from 1 week to 4 weeks compared to normal controls. p25 expression in 4-week diabetic rats was significantly higher than that of 2-week diabetic rats, and thermal PWL in 4-week diabetic rats showed delayed responses to painful thermal stimulation compared with those at 2 weeks. EA applied to the SP-9 point (2 Hz frequency) significantly prevented the thermal and mechanical hyperalgesia in the DNP rat. Additionally, EA combined with MK-801 prolonged anti-hyperalgesia, increased p35 expression, and decreased the cleavage of p35 to p25 during diabetic neuropathic pain. In this study we show EA combined with a sub-effective dose of MK-801 treatment in DNP induced by STZ that is related to p35/p25 expression in spinal cord.

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Section: Discussionmentioning

confidence: 99%

Antiallodynic Effects of Electroacupuncture Combined with MK-801 Treatment through the Regulation of p35/p25 in Experimental Diabetic Neuropathy

et al. 2011

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“…Additionally, NMDA receptor antagonists in combination with opioids have been indicated to be more effective than the former administered alone [16,[18][19][20][21][22][23][24][25] .…”

Section: Discussionmentioning

confidence: 99%

Magnesium Ions and Opioid Agonist Activity in Streptozotocin-Induced Hyperalgesia

Bujalska

Malinowska²,

Makulska-Nowak³

et al. 2008

Pharmacology

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Streptozotocin-induced hyperglycemia accompanied by a chronic decrease in the nociceptive threshold is considered a useful model of experimental hyperalgesia. We examined (1) the effect of the opioid receptor agonists and (2) the effect of the magnesium ions (Mg²⁺) on the antinociceptive action of opioid agonists in a diabetic neuropathic pain model. When administered alone, opioid agonists like morphine (5 mg/kg i.p.) and fentanyl (0.0625 mg/kg i.p.), as well as the partial agonist buprenorphine (0.075 mg/kg) had only little effect on streptozotocin-induced hyperalgesia. However, pretreatment with Mg²⁺ at a dose of 40 mg magnesium sulfate/kg i.p. markedly enhanced the analgesic activity of all three investigated opioids. Practical aspects of co-administration of magnesium and opioids in diabetic neuropathy are discussed.

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“…Memantine showed dose-dependent (1.8-17.8 mg/kg) symptomatic, anti-allodynic activity in the Bennett model of chronic constriction injury (CCI) [ 161 , 170 ] but there was little separation between anti-allodynic and rotarod effects. Co-administration with morphine or clonidine, each at 6 fixed equi-effective dose ratios, was not able to reveal any supra-additive i.e.…”

Section: Secondary Pharmacodynamicsmentioning

confidence: 99%

“…Co-administration with morphine or clonidine, each at 6 fixed equi-effective dose ratios, was not able to reveal any supra-additive i.e. synergistic effects (isobolographic analysis) [ 161 ]. In contrast, in this same sciatic nerve injury model, memantine had no symptomatic effects against either cold and mechanical allodynia – it should be noted that gabapentin was also inactive against mechanical allodynia in this study, but was active against cold allodynia [ 279 ].…”

Section: Secondary Pharmacodynamicsmentioning

confidence: 99%

Pharmacodynamics of Memantine: An Update

Rammes¹,

Danysz²,

Parsons

2008

149

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Memantine received marketing authorization from the European Agency for the Evaluation of Medicinal Products (EMEA) for the treatment of moderately severe to severe Alzheimer´s disease (AD) in Europe on 17 th May 2002 and shortly thereafter was also approved by the FDA for use in the same indication in the USA. Memantine is a moderate affinity, uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist with strong voltage-dependency and fast kinetics. Due to this mechanism of action (MOA), there is a wealth of other possible therapeutic indications for memantine and numerous preclinical data in animal models support this assumption. This review is intended to provide an update on preclinical studies on the pharmacodynamics of memantine, with an additional focus on animal models of diseases aside from the approved indication. For most studies prior to 1999, the reader is referred to a previous review [196].In general, since 1999, considerable additional preclinical evidence has accumulated supporting the use of memantine in AD (both symptomatic and neuroprotective). In addition, there has been further confirmation of the MOA of memantine as an uncompetitive NMDA receptor antagonist and essentially no data contradicting our understanding of the benign side effect profile of memantine. THERAPEUTIC TARGETThe maximal therapeutically-relevant plasma concentration of memantine is around 1 M (see [55,203]). Brain extracellular fluid (ECF) concentration of around 0.8 M can be anticipated [102] and any receptor that expresses an affinity at, or below, the very low M range should be considered as a potential therapeutic target. Given this assumption, there are only four plausible known target types to date: the most likely is the NMDA receptor channel, but 5-hydroxy-tryptamine (5-HT 3 ) receptors [220] and 7 and/or 4 2 nicotinic receptors [11] should also be taken into consideration [11,37,165].The 7 and 4 2 nicotinic acetylcholine receptor and the 5-HT 3 receptor systems have been suggested to play a role in modulating CNS functions, including learning and memory. These receptors are structurally related, containing large extracellular ligand-binding domains and four transmembrane domains that are largely conserved. They exhibit considerable cross-pharmacology, e.g. high concentrations of the 7 nAChR agonist nicotine inhibit 5-HT 3 receptor-mediated responses, and high concentrations of the 5-HT 3 receptor agonist serotonin inhibit 7 nAChR-mediated responses. Based on this knowledge, it seems reasonable to investigate whether ligands specific for either receptor, might have affinity for both. NMDA RECEPTORS Fast Kinetics and Strong Voltage-DependencyMemantine blocks the NMDA receptor channel in an use-dependent manner, meaning that it can only gain access to the channel in the presence of agonist and remains largely *Address correspondence to this author at Preclinical R & D, Merz Pharmaceuticals, Eckenheimer Landstrasse 100, 60318 Frankfurt am Main, Germany; Tel: +49 69 1503368; E-mail: christopher.parsons@m...

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Anti-allodynic interactions between NMDA receptor channel blockers and morphine or clonidine in neuropathic rats

Cited by 12 publications

References 27 publications

Antiallodynic Effects of Electroacupuncture Combined with MK-801 Treatment through the Regulation of p35/p25 in Experimental Diabetic Neuropathy

Antiallodynic Effects of Electroacupuncture Combined with MK-801 Treatment through the Regulation of p35/p25 in Experimental Diabetic Neuropathy

Magnesium Ions and Opioid Agonist Activity in Streptozotocin-Induced Hyperalgesia

Pharmacodynamics of Memantine: An Update

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