Neuroprotective and antioxidant activities of HU-211, a novel NMDA receptor antagonist

Eshhar, Nomi; Striem, S.; Kohen, Ron; Tirosh, Oren; Biegon, Anat

doi:10.1016/0014-2999(95)00271-l

Cited by 84 publications

(43 citation statements)

References 44 publications

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“…The plant cannabinoids, being monophenols, monophenolic ethers (like THC (1)), or resorcinols (as CBD (2)) are likewise potent anti-oxidants. Eshar et al [13] found that HU-211, a (þ)-THC-type cannabinoid, is a neuroprotective agent that combines NMDA-receptor antagonistic activity and free-radical-scavenging abilities in a single molecule. Following the same type of reasoning, Hampson et al [14] investigated the anti-oxidative properties of CBD, and recorded that it prevents hydroperoxide (H 2 O 2 )-induced oxidative damage equally well, or better, than ascorbate (vitamin C) or tocopherol (vitamin E).…”

mentioning

confidence: 98%

Cannabidiol – Recent Advances

Mechoulam

Peters

Murillo-Rodrı́guez

et al. 2007

Chemistry & Biodiversity

463

314

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The aim of this review is to present some of the recent publications on cannabidiol (CBD; 2), a major non-psychoactive constituent of Cannabis, and to give a general overview. Special emphasis is laid on biochemical and pharmacological advances, and on novel mechanisms recently put forward, to shed light on some of the pharmacological effects that can possibly be rationalized through these mechanisms. The plethora of positive pharmacological effects observed with CBD make this compound a highly attractive therapeutic entity.

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mentioning

confidence: 98%

Cannabidiol – Recent Advances

Mechoulam

Peters

Murillo-Rodrı́guez

et al. 2007

Chemistry & Biodiversity

463

314

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“…This reduction in calcium entry would also contribute to the antioxidant properties of the compound, although it would not completely account for them, because the antioxidant potential of dexanabinol is more pronounced than that of MK-801. 133,138 What contributes to this additional antioxidant effect is unclear, but it is likely to involve direct scavenging of free radicals or the ability to increase endogenous antioxidant ability. Whatever the antioxidant mechanism, it is known that dexanabinol protects cultured neurons from the toxic effects of ROS.…”

Section: Dexanabinolmentioning

confidence: 99%

“…134 -136 It is thought that the compound, which does not bind to the cannabinoid receptor, has a number of neuroprotective effects, including acting as an NMDA receptor antagonist, 137 a free radical scavenger and antioxidant, 138 and an inhibitor of cytokine TNF-␣. 139 Specifically, the dexanabinol molecule readily crosses the blood-brain barrier and weakly blocks NMDA receptors by interacting with a site close to, but distinct from, that of uncompetitive NMDA antagonists.…”

Section: Dexanabinolmentioning

confidence: 99%

Multifunctional Drugs for Head Injury

2009

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Summary: Traumatic brain injury (TBI) remains one of the leading causes of mortality and morbidity worldwide in individuals under the age of 45 years, and, despite extensive efforts to develop neuroprotective therapies, there has been no successful outcome in any trial of neuroprotection to date. In addition to recognizing that many TBI clinical trials have not been optimally designed to detect potential efficacy, the failures can be attributed largely to the fact that most of the therapies investigated have been targeted toward an individual injury factor. The contemporary view of TBI is that of a very heterogenous type of injury, one that varies widely in etiology, clinical presentation, severity, and pathophysiology. The mechanisms involved in neuronal cell death after TBI involve an interaction of acute and delayed anatomic, molecular, biochemical, and physiological events that are both complex and multifaceted. Accordingly, neuropharmacotherapies need to be targeted at the multiple injury factors that contribute to the secondary injury cascade, and, in so doing, maximize the likelihood of a successful outcome. This review focuses on a number of such multifunctional compounds that have shown considerable success in experimental studies and that show maximum promise for success in clinical trials.

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“…A synthetic cannabinoid (HU-211) also has been demonstrated to be neuroprotective even though it does not activate cannabinoid receptors. This compound is an atypical cannabinoid, however, in that it, unlike other cannabinoids, directly antagonizes NMDAr (10) and possesses some antioxidant properties (11). The present study examines classical cannabinoids as neuroprotectants in vitro but focuses on the nonpsychoactive cannabinoid cannabidiol.…”

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confidence: 99%

Cannabidiol and (−)Δ ⁹ -tetrahydrocannabinol are neuroprotective antioxidants

Hampson

Grimaldi

Axelrod

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

765

529

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The neuroprotective actions of cannabidiol and other cannabinoids were examined in rat cortical neuron cultures exposed to toxic levels of the excitatory neurotransmitter glutamate. Glutamate toxicity was reduced by both cannabidiol, a nonpsychoactive constituent of marijuana, and the psychotropic cannabinoid (؊)⌬ 9 -tetrahydrocannabinol (THC). Cannabinoids protected equally well against neurotoxicity mediated by N-methyl-D-aspartate receptors, 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid receptors, or kainate receptors. N-methyl-D-aspartate receptorinduced toxicity has been shown to be calcium dependent; this study demonstrates that 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid͞kainate receptor-type neurotoxicity is also calcium-dependent, partly mediated by voltage sensitive calcium channels. The neuroprotection observed with cannabidiol and THC was unaffected by cannabinoid receptor antagonist, indicating it to be cannabinoid receptor independent. Previous studies have shown that glutamate toxicity may be prevented by antioxidants. Cannabidiol, THC and several synthetic cannabinoids all were demonstrated to be antioxidants by cyclic voltametry. Cannabidiol and THC also were shown to prevent hydroperoxide-induced oxidative damage as well as or better than other antioxidants in a chemical (Fenton reaction) system and neuronal cultures. Cannabidiol was more protective against glutamate neurotoxicity than either ascorbate or ␣-tocopherol, indicating it to be a potent antioxidant. These data also suggest that the naturally occurring, nonpsychotropic cannabinoid, cannabidiol, may be a potentially useful therapeutic agent for the treatment of oxidative neurological disorders such as cerebral ischemia.Cannabinoid components of marijuana are known to exert behavioral and psychotropic effects but also to possess therapeutic properties including analgesia (1), ocular hypotension (2), and antiemesis (3). This report examines another potential therapeutic role for cannabinoids as neuroprotectants and describes their mechanism of action in rat cortical neuronal cultures.During an ischemic episode, large quantities of the excitatory neurotransmitter glutamate are released. This event causes neuronal death by over-stimulating N-methyl-Daspartate receptors (NMDAr) and 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid (AMPA) and kainatetype receptors and results in metabolic stress and accumulation of toxic levels of intracellular calcium (4). In vitro and in vivo studies (4,5,6) have demonstrated that such neurotoxicity can be reduced by antioxidants or antagonists to NMDAr and AMPA͞kainate receptors. Antioxidants such as ␣-tocopherol (5, 6) are effective neuroprotectants because of their ability to reduce the toxic reactive oxygen species (ROS) formed during ischemic metabolism. Cannabinoids like (Ϫ)⌬ 9

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Neuroprotective and antioxidant activities of HU-211, a novel NMDA receptor antagonist

Cited by 84 publications

References 44 publications

Cannabidiol – Recent Advances

Cannabidiol – Recent Advances

Multifunctional Drugs for Head Injury

Cannabidiol and (−)Δ ⁹ -tetrahydrocannabinol are neuroprotective antioxidants

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Neuroprotective and antioxidant activities of HU-211, a novel NMDA receptor antagonist

Cited by 84 publications

References 44 publications

Cannabidiol – Recent Advances

Cannabidiol – Recent Advances

Multifunctional Drugs for Head Injury

Cannabidiol and (−)Δ 9 -tetrahydrocannabinol are neuroprotective antioxidants

Contact Info

Product

Resources

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Cannabidiol and (−)Δ ⁹ -tetrahydrocannabinol are neuroprotective antioxidants