Effect of Agmatine on Acute and Mononeuropathic Pain

Arıcıoğlu, Feyza; Korcegez, Eylem; Bozkurt, Ayhan; Özyalçín, Süleyman

doi:10.1196/annals.1304.010

Cited by 32 publications

(14 citation statements)

References 40 publications

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“…It antagonizes a 2adrenoceptors, imidazoline receptors as well as Nmethyl-D-aspartate (NMDA) and glutamate receptors and inhibits nitric oxide synthase (NOS) [9]. Previous studies reported that agmatine has antinociceptive activity in several animal models of neuropathy or other behavioral models of pain [11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Agmatine co‐treatment attenuates allodynia and structural abnormalities in cisplatin‐induced neuropathy in rats

Dönertaş

Ünel

Aydın

et al. 2018

Fundamemntal Clinical Pharma

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Cisplatin is a widely used antineoplastic agent in the treatment of various cancers. Peripheral neuropathy is a well-known side effect of cisplatin and has potential to result in limiting and/or reducing the dose, decreasing the quality of life. Thus, effective treatments are needed. Agmatine is an endogenous neuromodulator that has been shown to exert antiallodynic effects in various animal studies. The first aim of this study was to investigate the in vitro effects of agmatine on cisplatin-induced neurotoxicity. Primary cultures of dorsal root ganglia (DRG) which are the primary target of drug injury were prepared. DRG cells were incubated with cisplatin (100, 200, 500 μm). Then, agmatine (10, 100, 500 μm) was administered with the submaximal concentration of cisplatin. Cisplatin caused concentration-dependent neurotoxicity, and agmatine did not alter this effect. The second aim was to investigate the effects of agmatine on cisplatin-induced peripheral neuropathy in rats and the influence of nitric oxide synthase (NOS) inhibitor, L-NAME, in this effect. Female Sprague Dawley rats received intraperitoneal saline (control), cisplatin (3 mg/kg), cisplatin+agmatine (100 mg/kg), or cisplatin+agmatine+L-NAME (10 mg/kg) once a week for 5 weeks. The mechanical allodynia, hot plate, and tail clip tests were performed, and DRG cells and sciatic nerves were analyzed. Agmatine and agmatine+L-NAME combination attenuated CIS-induced mechanical allodynia and degeneration in DRG cells and sciatic nerves. However, L-NAME did not potentiate the antiallodynic or neuroprotective effect of agmatine. These findings indicate that agmatine co-administration ameliorates cisplatin-induced neuropathy and may be a therapeutic alternative.

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Section: Introductionmentioning

confidence: 99%

Agmatine co‐treatment attenuates allodynia and structural abnormalities in cisplatin‐induced neuropathy in rats

Dönertaş

Ünel

Aydın

et al. 2018

Fundamemntal Clinical Pharma

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“…Our research group and others have demonstrated that exogenously administered agmatine has a variety of pharmacological effects related with central nervous system, such as nociception, neuroinjury/neuroprotection, cognition, epilepsy, opioid tolerance/ dependence, stress, anxiety, depression, and schizophrenia. Thus, agmatine can be a new candidate of novel therapeutic target by further revealing the underlying molecular mechanisms in related physiological and pathological conditions [20][21][22][23][24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Agmatine-attenuated cognitive and social deficits in subchronic MK-801 model of schizophrenia in rats

Ünal

Ateş

Arıcıoğlu

2018

Psychiatry and Clinical Psychopharmacology

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INTRODUCTION: Schizophrenia is one of the most severe psychiatric disorders with about 1% prevalence. It has been proved that glutamatergic N-methyl-D-aspartate (NMDA) receptor antagonists such as MK-801 and phencyclidine cause schizophrenia-like behaviours in rodents. Agmatine is an endogenous amine synthesized from decarboxylation of arginine and has been thought to be a neurotransmitter/neuromodulator. It binds to imidazoline and alfa adrenergic receptors and blocks cation channelled receptors, such as nicotinic acetylcholine, 5-HT3 serotonergic, and NMDA receptors. It is an endogenous inhibitor of nitric oxide synthase. A limited number of studies showed that agmatine attenuates sensorimotor gating deficit, which is an important parameter for schizophrenia, and improves cognitive deficits in rats. Despite this, it has also been shown that high doses of agmatine impaired sensorimotor gating. Herein, the aim of our study is to investigate the effect of subchronic agmatine treatment on sensorimotor gating, visual recognition memory, and social functions in subchronic MK-801 model of schizophrenia in rats. METHODS: Wistar Hannover rats were divided into four groups as control (dimethyl sulphoxide), MK-801 (0.2 mg/kg), MK-801 + agmatine (20 mg/kg), and MK-801 + risperidone (0.5 mg/kg)(n = 8 per group). MK-801 was subcutaneously injected once a day for 14 days. Agmatine and risperidone were administered intraperitoneally in the last seven days of MK-801 injections. On day 14, agmatine or risperidone was injected 15 minutes before MK-801 and MK-801 15 minutes before prepulse inhibition of the acoustic startle response (PPI) test. After the seven days washout period, social interaction (SI) test and novel object recognition test (NORT) were performed. One-way analysis of variance (ANOVA) or two-way ANOVA was used for statistical evaluation of NORT, SI, and PPI, respectively. Paired Student's t-test was used for the comparison of rat's affinity to a familiar and novel object in NORT. RESULTS: MK-801 administration significantly decreased prepulse inhibition of rats in the PPI test (p < .001). In addition to this, MK-801 decreased startle response to pulse-alone trials and increased basal activity measured by the magnitude of no stimulus trials compared to the control group (p < .05). Agmatine treatment did not improve MK-801-induced PPI, startle response, or basal activity deficits while risperidone blocked the disruptive effect of MK-801 (p < .05). In NORT, the MK-801 group had significantly lower discrimination index (p < .05), whereas both the agmatine and risperidone treatments substantially increased this index (p < .01). Moreover, MK-801 injections not only decreased sniffing (p < .01) and following (p < .01) behaviours but also increased avoiding behaviour (p < .001) in SI. Agmatine partially treated social deficits (p < .001) while risperidone was reversed all of them (p < .01). CONCLUSIONS: Subchronic MK-801 administration revealed sensorimotor gating, social and cognitive deficits in rats. Subchroni...

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“…Our group and other research groups have repeatedly demonstrated that exogenous agmatine has a variety of pharmacological effects improving a wide spectrum of central nervous system conditions, such as algesia including neuropathic pain , mood disorders , epilepsy , morphine type addiction , neuroinjury and cognition . Perhaps one of the most well‐established effects are antistress, anxiolytic and antidepressant‐like effects produced by agmatine .…”

mentioning

confidence: 98%

Agmatine Reverses Sub‐chronic Stress induced Nod‐like Receptor Protein 3 (NLRP3) Activation and Cytokine Response in Rats

Şahin

Albayrak

Akdeniz

et al. 2016

Basic Clin Pharma Tox

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The activation of Nod-like receptor protein 3 (NLRP3) has lately been implicated in stress and depression as an initiator mechanism required for the production of interleukin (IL)-1b and IL-18. Agmatine, an endogenous polyamine widely distributed in mammalian brain, is a novel neurotransmitter/neuromodulator, with antistress, anxiolytic and antidepressant-like effects. In this study, we examined the effect of exogenously administered agmatine on NLRP3 inflammasome pathway/cytokine responses in rats exposed to restraint stress for 7 days. The rats were divided into three groups: stress, stress+agmatine (40 mg/kg; i.p.) and control groups. Agmatine significantly down-regulated the gene expressions of all stress-induced NLRP3 inflammasome components (NLRP3, NF-jB, PYCARD, caspase-1, IL-1b and IL-18) in the hippocampus and prefrontal cortex (PFC) and reduced pro-inflammatory cytokine levels not only in both brain regions, but also in serum. Stress-reduced levels of IL-4 and IL-10, two major anti-inflammatory cytokines, were restored back to normal by agmatine treatment in the PFC. The findings of the present study suggest that stress-activated NLRP3 inflammasome and cytokine responses are reversed by an acute administration of agmatine. Whether antidepressant-like effect of agmatine can somehow, at least partially, be mediated by the inhibition of NLRP3 inflammasome cascade and relevant inflammatory responses requires further studies in animal models of depression.

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Effect of Agmatine on Acute and Mononeuropathic Pain

Cited by 32 publications

References 40 publications

Agmatine co‐treatment attenuates allodynia and structural abnormalities in cisplatin‐induced neuropathy in rats

Agmatine co‐treatment attenuates allodynia and structural abnormalities in cisplatin‐induced neuropathy in rats

Agmatine-attenuated cognitive and social deficits in subchronic MK-801 model of schizophrenia in rats

Agmatine Reverses Sub‐chronic Stress induced Nod‐like Receptor Protein 3 (NLRP3) Activation and Cytokine Response in Rats

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