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Organic Chemicals
Published in William J. Rea, Kalpana D. Patel, Reversibility of Chronic Disease and Hypersensitivity, Volume 4, 2017
William J. Rea, Kalpana D. Patel
Antagonists of the NMDA receptor are used as anesthetics for animals and sometimes humans, and are often used as recreational drugs due to their hallucinogenic properties, in addition to their unique effects at elevated dosages such as dissociation. When NMDA receptor antagonists are given to rodents in large doses, they can cause a form of brain damage called Olney's lesions. So far, the published research on Olney's lesions is inconclusive in its occurrence on human or monkey brain tissues with respect to an increase in the presence of NMDA receptor antagonists.26
Nonopiate Analgesics and Adjuvants
Published in Gary W. Jay, Practical Guide to Chronic Pain Syndromes, 2016
Other possible forms of adjunctive medications include NMDA receptor antagonists. There are no NMDA receptor antagonists approved for the treatment of pain; Memantine is approved for treatment of Alzheimer's disease. The NMDA receptor antagonists include ketamine, dextromethorphan, amantadine, magnesium, and methadone, an opiate which is considered to have a 10% NMDA receptor antagonism. These medications may, in the future, be very beneficial; particularly antagonists at the glycine-site NR2B sites, at which weak-binding channel blockers have shown an improved side effect profile in animal models of pain (33). Ketamine is used as an adjunctive therapy in the hospice setting when opioid therapy is not sufficient (34). Ketamine alone, or with midazolam, have long been used for sedating children undergoing minor operative procedures or painful procedures such as changing dressings for burn patients (35, 36).
Nonopiate Analgesics and Adjuvants
Published in Gary W. Jay, Clinician’s Guide to Chronic Headache and Facial Pain, 2016
Other possible forms of adjunctive medications include NMDA receptor antagonists. There are no NMDA receptor antagonists approved for the treatment of pain; Memantine is approved for treatment of Alzheimer’s disease. The NMDA receptor antagonists include ketamine, dextromethorphan, amantadine, magnesium, and methadone, an opiate which is considered to have a 10% NMDA receptor antagonism. These medications may, in the future, be very beneficial; particularly antagonists at the glycine-site NR2B sites, at which weak-binding channel blockers have shown an improved side effect profile in animal models of pain (33). Ketamine is used as an adjunctive therapy in the hospice setting when opioid therapy is not sufficient (34). Ketamine alone, or with midazolam, have long been used for sedating children undergoing minor operative procedures or painful procedures such as changing dressings for burn patients (35, 36).
Targeting metabotropic glutamate receptors in the treatment of epilepsy: rationale and current status
Published in Expert Opinion on Therapeutic Targets, 2019
Roberta Celli, Ines Santolini, Gilles Van Luijtelaar, Richard T Ngomba, Valeria Bruno, Ferdinando Nicoletti
Although glutamate is a main player of over-excitation in epilepsy, glutamate receptor antagonists were not successfully developed as antiepileptic drugs, with the notable exception of perampanel. One of the reasons is that iGlu receptor antagonists are not disease-dependent and cause a widespread inhibition of excitatory synaptic transmission in the CNS. In addition, NMDA receptor antagonists impair mechanisms of activity-dependent synaptic plasticity and may cause psychotomimetic effects. Targeting mGlu receptors with subtype-selective ligands (particularly, PAMs and NAMs) might offer a more favorable outcome in the treatment of epilepsy because mGlu receptors do not mediate, but rather modulate, synaptic transmission. Using these drugs, we expect a greater selectivity for overexcited neuronal networks (for example, the action of PAMs is activity-dependent), and a better profile of safety and tolerability.
Anti-nociceptive effects of low dose ketamine in mice may be mediated by the serotonergic systems
Published in Psychiatry and Clinical Psychopharmacology, 2019
Meral Erdinc, Emre Uyar, Ilker Kelle, Hasan Akkoc
Previous studies have reported that a variety of N-methyl-D-aspartate (NMDA) receptor antagonist drugs can induce antinociception [2,3]. Ketamine is a non-competitive NMDA receptor antagonist with unique properties. It was introduced almost half a century ago to serve as a mono anesthetic drug providing analgesia, amnesia, loss of consciousness and immobility [4]. However, reported significant side effects led to a diminishment in the role of ketamine in anesthesia [5]. It was continuously studied in the desire to find an alternative therapy to treat chronic and perioperative pain. Current research indicated that low-dose ketamine could produce profound analgesia with fewer side effects [6]. Despite that, the analgesic mechanism of action of ketamine is still not entirely clear.
The impact of a standardised ketamine step protocol for cancer neuropathic pain
Published in Progress in Palliative Care, 2022
Mahrley T. Provido-Aljibe, Choon Meng Yee, Zhi Jun Carin Low, Allyn Hum
Administration of ketamine, an NMDA receptor antagonist may lead to a number of side effects. Confusion, delirium, vivid dreams, hallucinations and feelings of detachment from the body are associated with ketamine use and are particularly prominent.27 In clinical practice, ketamine exposure is limited because of these side effects. In our ketamine step protocol, the side effects were not as pronounced due to the gradual stepwise increase in ketamine compared to the burst technique and the concurrent use of haloperidol 5 mg as a psychotropic agent. Cohen et al concluded that there was limited direct evidence supporting the prophylactic use of benzodiazepines, alpha-2 agonists, antidepressants, antihistamines, or anticholinergics prior to the initiation of sub-anesthetic ketamine for chronic pain treatment (grade C recommendation, low level of certainty). Nevertheless, it is noteworthy that most studies reviewed involved much higher doses of ketamine and benzodiazepines were the most common pre-medication. Haloperidol is still recommended as the first line agent in delirium management and the mean dose reported by Campbell et al in their systematic review was 6.5 mg over 24 hours.11,28,29 In our study, depressed consciousness, delirium and confusion were still observed even with the addition of parenteral haloperidol but not to the extent that patients needed to discontinue ketamine. We note a safe margin of tolerability evidenced by the low severity based on CTCAE grading for the documented side effects. More studies are needed to assess the effectiveness of psychotropics and benzodiazepines as pre-medications for ketamine in cancer pain.