NMDA receptor antagonists ketamine

The uncompetitive NMDA receptor antagonist ketamine has been available for clinical use as an anaesthetic for 40 years (Domino et al. 1965). Ketamine is effective in various animal models of hyperalgesia and allodynia and has been reported to have antinociceptive effects in some of these models at doses devoid of obvious side-effects. Others, however, have reported that the effects of ketamine are only seen at doses producing ataxia (see Parsons 2001 for review). Ketamine reportedly inhibits the area of secondary hyperalgesia induced by chemical (Park et al. 1995) or thermal stimuli (Ilkjaer et al. 1996 Warncke et al. 1997) and inhibits temporal siunmation of repeated mechanical (Warncke et al. 1997) and electrical stimuli (Arendtnielsen et al. 1995 Andersen et al. 

Rabben T. Effects of the NMDA receptor antagonist ketamine in electrically induced A delta-fiber pain. Methods Find Exp Clin Pharmacol 2000 22(3) 185-9. 

Eide, K., Stubhaug, A., Oye, I., Breivik, H., 1995. Continuous subcutaneous administration of the N-methyl-o-aspartic acid (NMDA) receptor antagonist ketamine in the treatment of post-herpetic neuralgia. Pain 61, 221-228. 

Memantine (Namenda) [Anti Alzheimer Agent/NMDA Receptor Antagonist] Uses Mod/ evere Alzheimer Dz Action N-methyl-D-aspartate recqjtor antagonist Dose Target 20 mg/d, start 5 mg/d, t 5 mg/d to 20 mg/d, wait >1 wk before t dose use doses if >5mg/d Caution [B, /-] Hqjatic/mild-mod renal impair Disp Tabs, sol SE Dizziness Interactions t Effects W amantadine, carbonic anhydrase inhibitors, dextromethorphan, ketamine, Na bicarbonate t effects W/ any drug, herb, food that alkalinizes urine EMS Use NaHCOs w/ caution OD May cause restlessness, hallucinations, drowsiness, and fainting symptomatic and supportive... 

Glutamate was initially implicated in schizophrenia by studies of the behavioral effects of N-methyl-D-aspartate (NMDA) receptor antagonists (e.g., PCP, ketamine), which produce psychotic symptoms and cognitive dysfunction in healthy subjects and exacerbate psychotic, negative, and cognitive symptoms in patients with schizophrenia. Studies show that acute administration of NMDA antagonists causes NMDA receptor dysfunction, resulting in decreased inhibition of subcortical dopamine neurons and consequent increased mesolimbic dopamine release. Chronic administration produces decreased release, or hypoactivity, of dopamine in the prefrontal cortex (Davis and Lieberman, 2000). 

Ketamine has been traditionally contraindicated in patients with increased ICP or reduced cerebral compliance because it increases CMR02, CBF and ICP. These deleterious effects can be antagonised by the concomitant administration of propofol, or thiopentone, and benzodiazepines. Furthermore, ketamine is an antagonist at the NMDA receptor. Nevertheless, ketamine can adversely affect neurological outcome in the presence of brain ischaemia. 

Warncke, T., Stubhaug, A., Jorum, E. Ketamine, an NMDA receptor antagonist, suppresses spatial and temporal properties of burn-induced secondary hyperalgesia in man a double-blind, cross-over comparison with morphine and placebo, Pain 1997, 72, 99-106. 

Another member of the arylcyclohexylamine structural class is ketamine, which is a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, meaning it disables certain higher-function signaling mechanisms in the brain (consciousness, memory, perception, and motor activity) from lower functions (breathing and heart rate). Ketamine is manufactured commercially for use as a surgical anesthetic for both humans and animals. 

Ketamine is a non-competitive N-methyl-D-aspar-tate (NMDA) receptor antagonist, meaning that it interferes with the brain s ability to receive, process, and broadcast certain signals. Specifically, ketamine interferes with the ability of the receptors to receive escitato-... 

One of the most popular hypotheses to explain schizophrenia, the glutamate hypothesis of schizophrenia, is based on the observation of psychotomimetic effects of noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists, such as phencyclidine (PCP), dizocilpine (MK-801), and ketamine. Like amphetamine, NMDA antagonists produce a psychosis-like state when administered to healthy individuals. Further... 

Subanesthetic low-dose ketamine is thought to cause delirium and disturbing dreaming. A systematic review of NMDA receptor antagonists in preventive analgesia has shown that only one of 20 studies documented adverse psychotomimetic effects attributable to ketamine (435). In that study, ketamine was given by the epidural route in a relatively high dose. 

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