NMDA antagonist

Similarly, W-methyl-D-aspartate (NMDA) antagonists 32 with analgesic activity were prepared, again using the Meth-Cohn quinoline synthesis as the key entry reaction, subsequent functional group manipulation giving the desired target compound. 

Several glutamate antagonists have been or are in the process of being evaluated both preclinically and clinically as neuroprotective agents. For example, MK-801, an NMDA antagonist, reduces the detrimental effects of excess glutamate (as well as other insults to neurons) in a variety of animal models. Unfortunately the... 

Abi-Saab WM, D Souza DC, Moghaddam B et al (1998) The NMDA antagonist model for schizophrenia promise and pitfalls. Pharmacopsychiatry (Suppl)31 104—109... 

Jevtovic-Todorovic V, Todorovic SM, Mennerick S, et al Nitrous oxide (laughing gas) is an NMDA antagonist, neuroprotectant and neurotoxin. Nat Med 4 460M63, 1998... 

Davis SM, Lees KR, Albers GW, Diener HC, Markabi S, Karlsson G, Norris J. Selfotel in acute ischemic stroke possible neurotoxic effects of an NMDA antagonist. Stroke 2000 31 347-354. 

In perhaps a more physiologic assessment of the nature of the PCP -NMDA interaction, we determined the effect of fixed concentrations of PCP and a classic NMDA antagonist (2-APV) on both ACh and DA... 

The current gold standard of treatment for cognitive symptoms includes pharmacologic management with a cholinesterase inhibitor and/or an N-methyl-D-aspartate (NMDA) antagonist. 

Surendran, N., et al. Evidence for overlapping substrate specificity between large neutral amino acid (LNAA) and dipeptide (hPEPTl) transporters for PD 158473, an NMDA antagonist. Pharm. Res. 1999, 16, 391-395. 

Even in Alzheimer s disease (AD), the possible involvement of a weak excitotoxic process cannot be ruled out. Indeed, mitochondrial abnormalities (such as cytochrome oxidase alterations) [36, 37] and increased levels of markers of oxidative stress [38] have been reported in AD. This has been the rationale for testing the NMDA antagonist memantine in Alzheimer s dementia [39]. 

Deutsch, S. I., Rosse, R. B. and Mastropaolo, J. Current status of NMDA antagonist interventions in the treatment of nonketotic hyperglycinemia. Clin. Neuropharmacol. 21 71-79,1998. 

Alcohol Ethanol GABAA channel, NMDA antagonist... 

Opioids also interact with excitatory amino acid neurotransmitters. At lower micromolar concentrations, p agonists (e.g., DAMGO) enhance NMDA activity in the nucleus accumbens, but inhibit non-NMDA activity (Martin et al. 1997). At higher concentrations (5 pM), NMDA currents are reduced. Conversely, central administration of glutamate can precipitate a withdrawal syndrome in morphine-dependent animals, similar to the opioid antagonist naloxone. NMDA mechanisms also appear to be involved in the development of morphine tolerance. Competitive and noncompetitive NMDA antagonists and inhibitors of nitric oxide synthase reduce or eliminate tolerance to morphine (Elliott et al. 1995 Bilsky et al. 1996). However, this does not occur for tolerance to k opioids. Pharmacokinetics... 

Motor effects Harmaline produces a motor tremor (8-14 Hz) through activation of cells in the inferior olive, which is blocked by noncompetitive NMDA antagonists (Du et al. 1997 Stanford and Fowler 1998). Harmaline tremor is also reversed by benzodiazepine agonists (Robertson 1980). The tremor is initiated by synchronous rhythms in the olivocere-bellar system and red nucleus (Lorden et al. 1988 Gogolak et al. 1977 Batini et al. 1980). The tremor is associated with increased cGMP in the cerebellum, and tolerance with a relative normalization of cGMP (Lutes et al. 1988). Rapid tolerance develops to this effect with repeated doses. 

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