N-Docosahexaenoylethanolamine (synaptamide): Carbon-14 radiolabeling and metabolic studies

Sonti, Shilpa; Duclos, R.; Tolia, Mansi; Gatley, S. John

doi:10.1016/j.chemphyslip.2017.11.002

Cited by 12 publications

(13 citation statements)

References 33 publications

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“…In vitro experiments showed that synaptamide activity is not blocked by cyclooxygenase and lipoxygenase, but decreases as a result of FAAH, which also confirms the hypothesis that synaptamide is the main metabolite that determines DHA neuroprotective activity [ 17 ]. In vivo studies using radioactive labels have shown that synaptamide accumulates to a greater extent in the brain than DHA after exogenous intake [ 34 ], which also explains the more pronounced activity. In our study, synaptamide administration prevented working spatial and long-term memory impairment in rats with neuropathic pain syndrome.…”

Section: Discussionmentioning

confidence: 99%

N-Docosahexaenoylethanolamine Attenuates Neuroinflammation and Improves Hippocampal Neurogenesis in Rats with Sciatic Nerve Chronic Constriction Injury

et al. 2020

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Chronic neuropathic pain is a condition that causes both sensory disturbances and a variety of functional disorders, indicating the involvement of various brain structures in pain pathogenesis. One of the factors underlying chronic neuropathic pain is neuroinflammation, which is accompanied by microglial activation and pro-inflammatory factor release. N-docosahexaenoylethanolamine (DHEA, synaptamide) is an endocannabinoid-like metabolite synthesized endogenously from docosahexaenoic acid. Synaptamide exhibits anti-inflammatory activity and improves neurite outgrowth, neurogenesis, and synaptogenesis within the hippocampus. This study aims to evaluate the effects of synaptamide obtained by the chemical modification of DHA, extracted from the Far Eastern raw material Berryteuthis magister on neuroinflammatory response and hippocampal neurogenesis changes during neuropathic pain. The study of microglial protein and cytokine concentrations was performed using immunohistochemistry and ELISA. The brain lipid analysis was performed using the liquid chromatography-mass spectrometry technique. Behavioral experiments showed that synaptamide prevented neuropathic pain-associated sensory and behavioral changes, such as thermal allodynia, impaired locomotor activity, working and long-term memory, and increased anxiety. Synaptamide attenuated microglial activation, release of proinflammatory cytokines, and decrease in hippocampal neurogenesis. Lipid analysis revealed changes in the brain N-acylethanolamines composition and plasmalogen concentration after synaptamide administration. In conclusion, we show here that synaptamide may have potential for use in preventing or treating neuropathic cognitive pain and emotional effects.

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Section: Discussionmentioning

confidence: 99%

N-Docosahexaenoylethanolamine Attenuates Neuroinflammation and Improves Hippocampal Neurogenesis in Rats with Sciatic Nerve Chronic Constriction Injury

et al. 2020

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“…A radiolabelling experiment showed DHEA was present in the brain between 15 s and 60 min following intravenous administration in male Swiss‐Webster mice, with the highest concentrations observed in the midbrain, brain stem and hypothalamus, and was significantly increased in the urine from 15 min (Sonti, Duclos, Tolia, & Gatley, 2017). Therefore, this suggests DHEA can rapidly cross the blood‐brain barrier and enter the brain tissue, however, there is no known study on the tissue concentrations or effects of DHEA when administered locally.…”

Section: Discussionmentioning

confidence: 99%

N‐docosahexaenoyl ethanolamine (synaptamide) has antinociceptive effects in male mice

Paton

Shirazi

Vyssotski

et al. 2020

European Journal of Pain

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Bioactive lipids have been identified as potential analgesics with excellent safety profiles and few side effects. The Nacylethanolamines (NAE) subclass is of particular interest, with one such compound, N-palmitoylethanolamine (PEA) used to treat allergic inflammatory skin conditions in veterinary clinics (Abramo et al., 2014; Cerrato et al., 2012; Noli et al., 2015) and as a 'nutraceutical' supplement (Hesselink, 2013). Another NAE compound is anandamide, the first endocannabinoid identified after the cannabinoid-1 (CB1) receptor was cloned (Devane et al.,

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“…It is also expected to display a substantial blood-brain barrier passage such as synaptamide. 21 Previous reports have shown that GPR110 activation by synaptamide leads to an increase of the cyclic adenosine monophosphate/protein kinase A signaling pathway and to attenuation of the expression of proinflammatory markers such as interleukin-1β (IL-1β), IL-6, tumor necrosis factor α, and nitric oxide synthetase 2. 22 In line with the anti-inflammatory effect mediated by synaptamide/GPR110 signaling, we demonstrated that GAO-3-02 concentration-dependently resolved the inflammatory response induced by IL-1β in immortalized human microglial cells (−85% at 150 nmol•L -1 , P < .0001).…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Progress report on new antiepileptic drugs: A summary of the Fifteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XV). I. Drugs in preclinical and early clinical development

Bialer

Johannessen

Koepp³

et al. 2020

Epilepsia

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Since 1992, the Eilat Conferences have provided a forum for all stakeholders in the epilepsy community to appraise the latest data on new antiepileptic drugs and emergency seizure treatments, including, in recent years, updates on progress with the development of novel monitoring and therapeutic devices. Because of the COVID-19 pandemic, the Fifteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XV) was held as a fully virtual conference on July 27-30, 2020 for the sessions on drugs and on August 3, 2020 for the sessions on devices, and was attended during the 5 days by >500 participants from 63 countries. This progress report summarizes key preclinical and initial (phase 1) clinical data on eight investigational treatments that are currently in early development, including 2-deoxy-D-glucose, GAO-3-02, JNJ-40411813, NBI-921352, NTX-001, sec-butylpropylacetamide, XEN1101, and XEN496. This report provides an overview of current scenarios in the area of treatment discovery and development. The information presented illustrates a variety of innovative strategies, including exploration of compounds with | 2341 BIALER Et AL. 1 | INTRODUCTION Despite the introduction of >20 second-generation antiepileptic drugs (AEDs) during the past 3 decades, including 10 new AEDs between 2008 and 2020, >30% of people with epilepsy do not attain seizure control with currently available medications, and for some epilepsy syndromes seizure outcome is even worse. 1 Hence, there is still an urgent need for newer, more effective treatments for epilepsy. Efforts to develop treatments with improved tolerability and safety are also warranted. Since 1992, the Eilat Conferences have provided a forum for stakeholders involved in clinical care, basic and clinical research, and regulatory agencies to meet on a biennial basis and discuss the latest advances in the discovery and development of new epilepsy treatments. Since 2016, sessions dedicated to discussion of novel therapeutic devices as well as devices for seizure monitoring were added to the Conferences' program. Because of the disruption caused by the COVID-19 pandemic, the 2020 Fifteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XV) was held virtually on July 27-30, 2020 for the sessions on drugs, and on August 3, 2020 for the sessions on devices. A total of 534 participants from 63 countries attended the conference, with about 75% of attendees being health care professionals/academic researchers and 25% being professionals working in the pharmaceutical industry. The virtual format did not prevent lively interactions among participants, and presenters were able to address in real time the many questions raised by the audience. Nevertheless, the face-to-face discussions, the social interaction, and the networking opportunities made possible by the physical presence of participants were surely missed. Accordingly, the Organizing Committee is confident that the next conference scheduled for 2022 will revert to the traditional format and unique boutique a...

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N-Docosahexaenoylethanolamine (synaptamide): Carbon-14 radiolabeling and metabolic studies

Cited by 12 publications

References 33 publications

N-Docosahexaenoylethanolamine Attenuates Neuroinflammation and Improves Hippocampal Neurogenesis in Rats with Sciatic Nerve Chronic Constriction Injury

N-Docosahexaenoylethanolamine Attenuates Neuroinflammation and Improves Hippocampal Neurogenesis in Rats with Sciatic Nerve Chronic Constriction Injury

N‐docosahexaenoyl ethanolamine (synaptamide) has antinociceptive effects in male mice

Progress report on new antiepileptic drugs: A summary of the Fifteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XV). I. Drugs in preclinical and early clinical development

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