Chemistry:Traxoprodil

From HandWiki
Short description: Chemical compound
Traxoprodil
Traxoprodil.svg
Clinical data
Other namesCP-101606
ATC code
  • None
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC20H25NO3
Molar mass327.424 g·mol−1
3D model (JSmol)
 ☒N☑Y (what is this?)  (verify)

Traxoprodil (developmental code name CP-101606) 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.

Traxoprodil showed ketamine-like rapidly-acting antidepressant effects in a small clinical trial of 30 patients with depression who were non-responders to 6 weeks of paroxetine treatment.[15] The response rate was 60%, relative to 20% for placebo, and 33% of the participants met remission criteria by day five following a single administration.[15] After one week, 78% of responders still showed an antidepressant response, and after 15 days, 42% did so.[15] In the study, half of the participants had to have their dose lowered due to a high incidence of dissociative side effects at the higher doses.[15] Development was stopped due to incidence of QTc prolongation.[15] Other NR2B subunit-selective antagonists of the NMDA receptor are still under development for depression, such as rislenemdaz (CERC-301, MK-0657).[15]

See also

References

  1. ↑ "(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. August 1995. doi:10.1021/jm00016a017. PMID 7636876. 
  2. ↑ "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. September 1997. doi:10.1073/pnas.94.20.11019. PMID 9380752. Bibcode: 1997PNAS...9411019B. 
  3. ↑ "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. November 1997. doi:10.1161/01.str.28.11.2244. PMID 9368572. 
  4. ↑ "Antinociceptive activity of CP-101,606, an NMDA receptor NR2B subunit antagonist". British Journal of Pharmacology 122 (5): 809–12. November 1997. doi:10.1038/sj.bjp.0701445. PMID 9384494. 
  5. ↑ "Antiparkinsonian actions of CP-101,606, an antagonist of NR2B subunit-containing N-methyl-d-aspartate receptors". Experimental Neurology 163 (1): 239–43. May 2000. doi:10.1006/exnr.2000.7374. PMID 10785463. 
  6. ↑ "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. August 2004. doi:10.1016/j.expneurol.2004.05.004. PMID 15246846. 
  7. ↑ "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 (1): 42–50. 1999. doi:10.1111/j.1749-6632.1999.tb07979.x. PMID 10668412. Bibcode: 1999NYASA.890...42M. 
  8. ↑ Chazot PL (November 2000). "CP-101606 Pfizer Inc". Current Opinion in Investigational Drugs 1 (3): 370–4. PMID 11249721. 
  9. ↑ "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. January 2004. doi:10.1089/089771504772695977. PMID 14987468. 
  10. ↑ "NMDA/NR2B selective antagonists in the treatment of ischemic brain injury". Current Drug Targets. CNS and Neurological Disorders 4 (2): 143–51. April 2005. doi:10.2174/1568007053544183. PMID 15857299. 
  11. ↑ "The effect of the selective NMDA receptor antagonist traxoprodil in the treatment of traumatic brain injury". Journal of Neurotrauma 22 (12): 1428–43. December 2005. doi:10.1089/neu.2005.22.1428. PMID 16379581. 
  12. ↑ "Chapter 3: Epilepsy". Ionotropic Glutamate Receptors as Therapeutic Targets. FP Graham Publishing Co., Johnson City, TN. 2002. pp. 91–132. http://works.bepress.com/michael_rogawski/25/. 
  13. ↑ "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. December 2008. doi:10.1097/JCP.0b013e31818a6cea. PMID 19011431. 
  14. ↑ "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. December 2007. doi:10.1097/FBP.0b013e3282f14ed6. PMID 17989511. 
  15. ↑ 15.0 15.1 15.2 15.3 15.4 15.5 "New targets for rapid antidepressant action". Prog. Neurobiol. 152: 21–37. 2017. doi:10.1016/j.pneurobio.2015.12.001. PMID 26724279. 



Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:Traxoprodil&oldid=3711391"