Agmatine, a potential novel therapeutic strategy for depression

Freitas, Andiara E.; Neis, Vivian B.; Rodrigues, Ana Lúcia S.

doi:10.1016/j.euroneuro.2016.10.013

Cited by 44 publications

(16 citation statements)

References 183 publications

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“…An intake of more than 1 kg of alfalfa microgreens (FW) would be necessary to reach an equivalent level, which is unrealistic. However, some rodent experiments [42] have shown that oral administration of 0.1 mg/kg of AGM alone produces the antidepressant effects. If similar results are confirmed in human studies, this would put a different perspective on alfalfa sprouts as a source of dietary AGM.…”

Section: Alfalfamentioning

confidence: 99%

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Accumulation of Agmatine, Spermidine, and Spermine in Sprouts and Microgreens of Alfalfa, Fenugreek, Lentil, and Daikon Radish

Cigić

Rupnik

Rijavec

et al. 2020

Foods

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Sprouts and microgreens are a rich source of various bioactive compounds. Seeds of lentil, fenugreek, alfalfa, and daikon radish seeds were germinated and the contents of the polyamines agmatine (AGM), putrescine (PUT), cadaverine (CAD), spermidine (SPD), and spermine (SPM) in ungerminated seeds, sprouts, and microgreens were determined. In general, sprouting led to the accumulation of the total polyamine content. The highest levels of AGM (5392 mg/kg) were found in alfalfa microgreens, PUT (1079 mg/kg) and CAD (3563 mg/kg) in fenugreek sprouts, SPD (579 mg/kg) in lentil microgreens, and SPM (922 mg/kg) in fenugreek microgreens. A large increase in CAD content was observed in all three legume sprouts. Conversely, the nutritionally beneficial polyamines AGM, SPD, and SPM were accumulated in microgreens, while their contents of CAD were significantly lower. In contrast, daikon radish sprouts exhibited a nutritionally better profile of polyamines than the microgreens. Freezing and thawing of legume sprouts resulted in significant degradation of CAD, PUT, and AGM by endogenous diamine oxidases. The enzymatic potential of fenugreek sprouts can be used to degrade exogenous PUT, CAD, and tyramine at pH values above 5.

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Section: Alfalfamentioning

confidence: 99%

“…Fermented food, various sprouts [16,39] Fermented foods, Citrus fruits and vegetables, legumes [38,40,41] Fermented foods, legume sprouts [16,42] Legumes, brassica vegetables, mushrooms, cheese [38,40] Liver, meat,…”

Section: Main Dietary Sourcesmentioning

confidence: 99%

Accumulation of Agmatine, Spermidine, and Spermine in Sprouts and Microgreens of Alfalfa, Fenugreek, Lentil, and Daikon Radish

Cigić

Rupnik

Rijavec

et al. 2020

Foods

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“…45 In the CNS, it is especially present in the cytoplasm in a network of neurons in the rostral brainstem and forebrain. 46 Noteworthy, agmatine is postulated to be a neuromodulator 47 that is taken up by presynaptic axon terminals, stored in synaptic vesicles (even as with other neurotransmitters such glutamate), and released upon membrane depolarization, [48][49][50] similar to classical neurotransmitters. Despite these features, no well-characterized receptor for agmatine was reported yet.…”

Section: Agmatinementioning

confidence: 99%

Novel Targets for Fast Antidepressant Responses: Possible Role of Endogenous Neuromodulators

Camargo

Rodrigues

2019

Chronic Stress

Self Cite

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The available medications for the treatment of major depressive disorder have limitations, particularly their limited efficacy, delayed therapeutic effects, and the side effects associated with treatment. These issues highlight the need for better therapeutic agents that provide more efficacious and faster effects for the management of this disorder. Ketamine, an N-methyl-D-aspartate receptor antagonist, is the prototype for novel glutamate-based antidepressants that has been shown to cause a rapid and sustained antidepressant effect even in severe refractory depressive patients. Considering the importance of these findings, several studies have been conducted to elucidate the molecular targets for ketamine’s effect. In addition, efforts are under way to characterize ketamine-like drugs. This review focuses particularly on evidence that endogenous glutamatergic neuromodulators may be able to modulate mood and to elicit fast antidepressant responses. Among these molecules, agmatine and creatine stand out as those with more published evidence of similarities with ketamine, but guanosine and ascorbic acid have also provided promising results. The possibility that these neuromodulators and ketamine have common neurobiological mechanisms, mainly the ability to activate mechanistic target of rapamycin and brain-derived neurotrophic factor signaling, and synthesis of synaptic proteins in the prefrontal cortex and/or hippocampus is presented and discussed.

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“…Agmatine administration to laboratory rodents modulates ethanol-induced anxiolysis and withdrawal anxiety [21], nicotine sensitization, and compulsive behaviors [21][22][23]. Injection of agmatine also produces anticonvulsant, antineurotoxic, and antidepressant-like actions in animals [24][25][26][27]. In recent years the number of studies with animal models has increased; these have demonstrated beneficial effects of agmatine administration for the following disorders: anxiety, hypoxic ischemia, nociception,…”

Section: Accepted Manuscript Introductionmentioning

confidence: 99%

Metabolic strategies for the degradation of the neuromodulator agmatine in mammals

et al. 2018

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Agmatine (1-amino-4-guanidinobutane), a precursor for polyamine biosynthesis, has been identified as an important neuromodulator with anticonvulsant, antineurotoxic and antidepressant actions in the brain. In this context it has emerged as an important mediator of addiction/satiety pathways associated with alcohol misuse. Consequently, the regulation of the activity of key enzymes in agmatine metabolism is an attractive strategy to combat alcoholism and related addiction disorders. Agmatine results from the decarboxylation of L-arginine in a reaction catalyzed by arginine decarboxylase (ADC), and can be converted to either guanidine butyraldehyde by diamine oxidase (DAO) or putrescine and urea by the enzyme agmatinase (AGM) or the more recently identified AGM-like protein (ALP). In rat brain, agmatine, AGM and ALP are predominantly localised in areas associated with roles in appetitive and craving (drug-reinstatement) behaviors. Thus, inhibitors of AGM or ALP are promising agents for the treatment of addictions. In this review, the properties of DAO, AGM and ALP are discussed with a view to their role in the agmatine metabolism in mammals.

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Agmatine, a potential novel therapeutic strategy for depression

Cited by 44 publications

References 183 publications

Accumulation of Agmatine, Spermidine, and Spermine in Sprouts and Microgreens of Alfalfa, Fenugreek, Lentil, and Daikon Radish

Accumulation of Agmatine, Spermidine, and Spermine in Sprouts and Microgreens of Alfalfa, Fenugreek, Lentil, and Daikon Radish

Novel Targets for Fast Antidepressant Responses: Possible Role of Endogenous Neuromodulators

Metabolic strategies for the degradation of the neuromodulator agmatine in mammals

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