While human studies remain far and few between (
I think this is the most recent), there have been some recent mouse/cell studies:
Agmatine as a novel candidate for rapid-onset antidepressant response
Major depressive disorder (MDD) is a disabling and highly prevalent mood disorder as well as a common cause of suicide. Chronic stress, inflammation, and intestinal dysbiosis have all been shown to play crucial roles in the pathophysiology of MDD. Although conventional antidepressants are widely used in the clinic, they can take weeks to months to produce therapeutic effects. The discovery that ketamine promotes fast and sustaining antidepressant responses is one of the most important breakthroughs in the pharmacotherapy of MDD. However, the adverse psychomimetic/dissociative and neurotoxic effects of ketamine discourage its chronic use. Therefore, agmatine, an endogenous glutamatergic modulator, has been postulated to elicit fast behavioral and synaptogenic effects by stimulating the mechanistic target of rapamycin complex 1 signaling pathway, similar to ketamine. However, recent evidence has demonstrated that the modulation of the NLR family pyrin domain containing 3 inflammasome and gut microbiota, which have been shown to play a crucial role in the pathophysiology of MDD, may also participate in the antidepressant-like effects of both ketamine and agmatine. This review seeks to provide evidence about the mechanisms that may underlie the fast antidepressant-like responses of agmatine in preclinical studies. Considering the anti-inflammatory properties of agmatine, it may also be further investigated as a useful compound for the management of MDD associated with a pro-inflammatory state. Moreover, the fast antidepressant-like response of agmatine noted in animal models should be investigated in clinical studies.
Major depressive disorder (MDD) is a disabling and highly prevalent mood disorder as well as a common cause of suicide. Chronic stress, inflammation, and intestinal dysbiosis have all been shown to play crucial roles in the pathophysiology of MDD. Although conventional antidepressants are widely...
pubmed.ncbi.nlm.nih.gov
Agmatine prevents development of tolerance to anti-nociceptive effect of ethanol in mice
Drug tolerance is directly correlated with drug abuse and physical dependence. The development of tolerance is manifested as the decline in pharmacological responses of drugs following repeated administration of the constant dose. The present study evaluated the effect of agmatine in ethanol-induced anti-nociception and tolerance in the tail-flick assay in mice. In an acute protocol, ethanol (1 and 2 g/kg, i.p. [intraperitoneally]) and agmatine (20 and 40 μg/mouse, i.c.v. [intracerebroventricularly]) produced significant analgesic effects in mice, as was evident from the increased baseline tail-flick latency when tested 20 minutes after their administration. Agmatine in a per se non-effective dose (5 μg/mouse, i.c.v.), L-arginine (40 μg/mouse, i.c.v.), and arcaine (25 μg/mouse, i.c.v.) significantly potentiated the anti-nociceptive effect of ethanol. Blood ethanol analysis showed no significant differences in blood ethanol concentration between ethanol/saline- and ethanol/agmatine-treated mice, suggesting that the effects of agmatine were not due to any possible effects on the pharmacokinetics of ethanol. In a separate study, mice were injected with ethanol (2 g/kg, i.p., 12%) or saline (1 mL/kg, i.p.) once daily for 9 days. On days 1, 3, 5, 7, and 9 of the experiment, they were subjected to the tail-flick test. Agmatine (5-20 μg/mouse, i.c.v.), L-arginine (40 μg/mouse, i.c.v.), arcaine (25 μg/mouse, i.c.v.), aCSF (2 μL/mouse, i.c.v.), or saline (1 mL/kg, i.p.) was administered daily prior to the first daily ethanol or saline injections, and reaction latencies were determined in the tail-flick assay. Injections of agmatine, L-arginine, and arcaine prevented the development of tolerance to ethanol-induced analgesia. Given that agmatine and its endogenous modulation can prevent tolerance to the anti-nociceptive effects of ethanol, these data suggest it as a possible new therapeutic strategy for the treatment of alcohol use disorder and associated complications.
Drug tolerance is directly correlated with drug abuse and physical dependence. The development of tolerance is manifested as the decline in pharmacological responses of drugs following repeated administration of the constant dose. The present study evaluated the effect of agmatine in...
pubmed.ncbi.nlm.nih.gov
Effect of Agmatine on a mouse model of allergic airway inflammation: A comparative study
Introduction: Asthma is a chronic lung disease that injures and constricts the airways. This study evaluates the effects of agmatine on ovalbumin (OVA)-induced allergic inflammation of the airways.
Methods: OVA sensitization by intraperitoneal injection was used to induce airway inflammation in mice on days 0 and 7; then the mice were challenged using beclomethasone (150 µg/kg, inhalation), a standard anti-asthmatic drug, from day 14 to day 16. Furthermore, agmatine (200 mg/kg) was intraperitoneally injected on day 0 and then daily for 16 days, followed by OVA challenge. The lung weight ratio, total and differential cell counts, TNF-α, interleukin-5 (IL-5) and IL-13 in bronchoalveolar lavage fluid (BALF), lung nitrite/nitrate (NO), and oxidative parameters were determined. Moreover, histopathological and immunohistochemical staining was employed.
Results: Injection of agmatine (200 mg/kg) for 16 days significantly attenuated inflammation of the airways. The levels of BALF inflammatory cells, TNF-α, IL-5, IL-13, lung NO, and malondialdehyde (MDA), significantly decreased with concomitant elevation of superoxide dismutase (SOD) levels. Histological and immunohistochemical analyses of mast cells paralleled to biochemical improvements.
Conclusion: Finally, this study illustrated that agmatine attenuates the allergic inflammation of airways caused by OVA by mitigating cytokines release, NO expression, and oxidative stress.
Finally, this study illustrated that agmatine attenuates the allergic inflammation of airways caused by OVA by mitigating cytokines release, NO expression, and oxidative stress.
pubmed.ncbi.nlm.nih.gov
Transcriptomics combined with metabolomics analysis of the mechanism of agmatine in the treatment of septic liver injury
Abstract
Background: Acute liver injury can occur at any stage of sepsis and is an important sign of multiple organ dysfunction syndrome (MODS). Studies have shown that agmatine (AGM) can effectively improve liver injury caused by sepsis. However, due to the numerous metabolites and metabolic pathways of AGM in the human body, its mechanism in treating septic liver injury is unclear.
Methods: In this study, a liver injury model of septic Sprague-Dawley rats was established by cecal ligation and perforation (CLP). After AGM treatment, transcriptomics combined with metabolomics was employed to analyze the gene expression levels and metabolite changes.
Results: The results showed that AGM decreased the expression levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), procalcitonin (PCT), and inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β)] in the serum of septic rats. It also reduced liver inflammatory cell infiltration and abnormal lipid metabolism, and promoted the survival rate of septic rats. In addition, 17 differentially-expressed genes were identified by transcriptomics, mainly in arginine and proline metabolism, the arachidonic acid metabolism pathway, as well as the nuclear factor kappa B (NF-κB) and AMP-activated protein kinase (AMPK)-peroxisome proliferator-activated receptor α (PPARα) signal transduction pathways. Metabolomics analysis was carried out to study the potential liver metabolism spectrum changes induced by AGM treatment. The results showed significant changes in 26 metabolites in the rat liver samples, mainly involved in arginine and proline metabolism, arachidonic acid metabolism, linoleic acid metabolism, and fatty acid metabolism.
Conclusions: The integrated transcriptomics and metabolomics analysis demonstrated that AGM improved septic liver injury by regulating lipid metabolism, and reduced the inflammatory reaction by affecting fatty acid metabolism, amino acid metabolism, and the arachidonic acid metabolism pathway. The integration of transcriptomics and metabolomics provides an effective means to elucidate AGM's therapeutic pathways and biomarkers.
Acute liver injury can occur at any stage of sepsis and is an important sign of multiple organ dysfunction syndrome (MODS). Studies have shown that agmatine (AGM) can effectively improve liver injury caused by sepsis. However, due to the numerous metabolites ...
www.ncbi.nlm.nih.gov
The memory modulatory effect of agmatine in passive avoidance task coincides with alterations of hippocampal CaMKII-α and ERK signaling in mice
Abstract
Agmatine is a polyamine suggested to act as a supposed neurotransmitter in the brain. Evidence has indicated that acute agmatine administration might modulate memory. The present study aimed to investigate the effect of repeated agmatine treatment on passive avoidance memory, hippocampal calcium-calmodulin-dependent protein kinase II-alpha (CaMKII-α), and Extracellular Signal-Regulated Kinase (ERK) signaling pathways in naive mice. Adult male NMRI mice were treated with agmatine (10, 20, 30, 40, and 80 mg/kg/ip) or saline for 11 days. Acquisition and retention tests of passive avoidance memory were performed on days 10 and 11, respectively. Following the memory retention test, the hippocampi were assessed for the levels of CaMKII-α and ERK using the western blotting technique. The results revealed the dose-dependent effect of agmatine on the passive avoidance memory. Accordingly, the memory was impaired in lower doses, but was improved in higher ones. Agmatine in none of the doses affected the nociception of the mice in tail-flick test. Furthermore, agmatine increased the phosphorylation of CaMKII-α and ERK in the hippocampus at memory enhancing doses, while ERK phosphorylation decreased following the impairing doses of agmatine. Thus, the dose-dependent effect of agmatine on memory might be related to its modulatory effect on CaMKII-α and ERK signal transduction, eventually regulating the memory process.
Agmatine is a polyamine suggested to act as a supposed neurotransmitter in the brain. Evidence has indicated that acute agmatine administration might modulate memory. The present study aimed to investigate the effect of repeated agmatine treatment on passive avoidance memory, hippocampal...
pubmed.ncbi.nlm.nih.gov
