Traxoprodil

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Traxoprodil
Traxoprodil.svg
Systematic (IUPAC) name
(1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol
Clinical data
Legal status
?
Identifiers
CAS number 134234-12-1 N
189894-57-3 (methanesulphonate)
ATC code None
PubChem CID 219101
ChemSpider 189919 YesY
UNII UTC046R5HM YesY
KEGG D06204 N
ChEMBL CHEMBL17350 YesY
Synonyms Traxoprodil, CP-101,606
Chemical data
Formula C20H25NO3 
Mol. mass 327.416 g/mol
 N (what is this?)  (verify)

Traxoprodil (CP-101,606) is a drug developed by Pfizer which acts as an NMDA antagonist, selective for the NR2B subunit.[1][2] It has neuroprotective,[3] analgesic,[4] and anti-Parkinsonian effects in animal studies.[5][6] Traxoprodil has been researched in humans as a potential treatment to lessen the damage to the brain after stroke,[7][8][9][10] but results from clinical trials showed only modest benefit.[11]The drug was found to cause EKG abnormalities (QT prolongation) and its clinical development was stopped.[12] More recent animal studies have suggested traxoprodil may exhibit rapid-acting antidepressant effects similar to those of ketamine,[13] although there is some evidence for similar psychoactive side effects and abuse potential at higher doses,[14] which might limit clinical acceptance of traxoprodil for this application.

See also[edit]

References[edit]

  1. ^ Chenard BL, Bordner J, Butler TW, Chambers LK, Collins MA, De Costa DL, Ducat MF, Dumont ML, Fox CB, Mena EE (August 1995). "(1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol: a potent new neuroprotectant which blocks N-methyl-D-aspartate responses". Journal of Medicinal Chemistry 38 (16): 3138–45. doi:10.1021/jm00016a017. PMID 7636876. 
  2. ^ Brimecombe JC, Boeckman FA, Aizenman E (September 1997). "Functional consequences of NR2 subunit composition in single recombinant N-methyl-D-aspartate receptors". Proceedings of the National Academy of Sciences of the United States of America 94 (20): 11019–24. doi:10.1073/pnas.94.20.11019. PMC 23569. PMID 9380752. 
  3. ^ Di X, Bullock R, Watson J, Fatouros P, Chenard B, White F, Corwin F (November 1997). "Effect of CP101,606, a novel NR2B subunit antagonist of the N-methyl-D-aspartate receptor, on the volume of ischemic brain damage off cytotoxic brain edema after middle cerebral artery occlusion in the feline brain". Stroke; a Journal of Cerebral Circulation 28 (11): 2244–51. doi:10.1161/01.str.28.11.2244. PMID 9368572. 
  4. ^ Taniguchi K, Shinjo K, Mizutani M, Shimada K, Ishikawa T, Menniti FS, Nagahisa A (November 1997). "Antinociceptive activity of CP-101,606, an NMDA receptor NR2B subunit antagonist". British Journal of Pharmacology 122 (5): 809–12. doi:10.1038/sj.bjp.0701445. PMC 1565002. PMID 9384494. 
  5. ^ Steece-Collier K, Chambers LK, Jaw-Tsai SS, Menniti FS, Greenamyre JT (May 2000). "Antiparkinsonian actions of CP-101,606, an antagonist of NR2B subunit-containing N-methyl-d-aspartate receptors". Experimental Neurology 163 (1): 239–43. doi:10.1006/exnr.2000.7374. PMID 10785463. 
  6. ^ Nash JE, Ravenscroft P, McGuire S, Crossman AR, Menniti FS, Brotchie JM (August 2004). "The NR2B-selective NMDA receptor antagonist CP-101,606 exacerbates L-DOPA-induced dyskinesia and provides mild potentiation of anti-parkinsonian effects of L-DOPA in the MPTP-lesioned marmoset model of Parkinson's disease". Experimental Neurology 188 (2): 471–9. doi:10.1016/j.expneurol.2004.05.004. PMID 15246846. 
  7. ^ Merchant RE, Bullock MR, Carmack CA, Shah AK, Wilner KD, Ko G, Williams SA (1999). "A double-blind, placebo-controlled study of the safety, tolerability and pharmacokinetics of CP-101,606 in patients with a mild or moderate traumatic brain injury". Annals of the New York Academy of Sciences 890: 42–50. doi:10.1111/j.1749-6632.1999.tb07979.x. PMID 10668412. 
  8. ^ Chazot PL (November 2000). "CP-101606 Pfizer Inc". Current Opinion in Investigational Drugs (London, England : 2000) 1 (3): 370–4. PMID 11249721. 
  9. ^ Kundrotiene J, Cebers G, Wägner A, Liljequist S (January 2004). "The NMDA NR2B subunit-selective receptor antagonist, CP-101,606, enhances the functional recovery the NMDA NR2B subunit-selective receptor and reduces brain damage after cortical compression-induced brain ischemia". Journal of Neurotrauma 21 (1): 83–93. doi:10.1089/089771504772695977. PMID 14987468. 
  10. ^ Wang CX, Shuaib A (April 2005). "NMDA/NR2B selective antagonists in the treatment of ischemic brain injury". Current Drug Targets. CNS and Neurological Disorders 4 (2): 143–51. doi:10.2174/1568007053544183. PMID 15857299. 
  11. ^ Yurkewicz L, Weaver J, Bullock MR, Marshall LF (December 2005). "The effect of the selective NMDA receptor antagonist traxoprodil in the treatment of traumatic brain injury". Journal of Neurotrauma 22 (12): 1428–43. doi:10.1089/neu.2005.22.1428. PMID 16379581. 
  12. ^ Löscher W, Rogawski MA (2002). "Chapter 3: Epilepsy". In Lodge D, Danysz W, Parsons CG. ["http://works.bepress.com/michael_rogawski/25/" Ionotropic Glutamate Receptors as Therapeutic Targets]. FP Graham Publishing Co., Johnson City, TN. pp. 91–132. 
  13. ^ Preskorn SH, Baker B, Kolluri S, Menniti FS, Krams M, Landen JW (December 2008). "An innovative design to establish proof of concept of the antidepressant effects of the NR2B subunit selective N-methyl-D-aspartate antagonist, CP-101,606, in patients with treatment-refractory major depressive disorder". Journal of Clinical Psychopharmacology 28 (6): 631–7. doi:10.1097/JCP.0b013e31818a6cea. PMID 19011431. 
  14. ^ Nicholson KL, Mansbach RS, Menniti FS, Balster RL (December 2007). "The phencyclidine-like discriminative stimulus effects and reinforcing properties of the NR2B-selective N-methyl-D-aspartate antagonist CP-101 606 in rats and rhesus monkeys". Behavioural Pharmacology 18 (8): 731–43. doi:10.1097/FBP.0b013e3282f14ed6. PMID 17989511.