Surf Wiki
Save to docs
general/4-phenylpiperidines

From Surf Wiki (app.surf) — the open knowledge base

Traxoprodil

Chemical compound

Chemical compound

| elimination_half-life =

189894-57-3 (methanesulphonate)

Traxoprodil (developmental code name CP-101606) is a drug developed by Pfizer which acts as an NMDA antagonist, selective for the NR2B subunit. It has neuroprotective, analgesic, and anti-Parkinsonian effects in animal studies. Traxoprodil has been researched in humans as a potential treatment to lessen the damage to the brain after stroke, but results from clinical trials showed only modest benefit. The drug was found to cause EKG abnormalities (QT prolongation) and its clinical development was stopped. More recent animal studies have suggested traxoprodil may exhibit rapid-acting antidepressant effects similar to those of ketamine, although there is some evidence for similar psychoactive side effects and abuse potential at higher doses, 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. 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. After one week, 78% of responders still showed an antidepressant response, and after 15 days, 42% did so. 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. Development was stopped due to incidence of QTc prolongation. Other NR2B subunit-selective antagonists of the NMDA receptor are still under development for depression, such as rislenemdaz (CERC-301, MK-0657).

Chemically, traxoprodil is a substituted phenethylamine and β-hydroxyamphetamine derivative.

References

References

  1. (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.
  2. (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.
  3. (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.
  4. (November 1997). "Antinociceptive activity of CP-101,606, an NMDA receptor NR2B subunit antagonist". [[British Journal of Pharmacology]].
  5. (May 2000). "Antiparkinsonian actions of CP-101,606, an antagonist of NR2B subunit-containing N-methyl-d-aspartate receptors". Experimental Neurology.
  6. (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.
  7. (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.
  8. Chazot PL. (November 2000). "CP-101606 Pfizer Inc". Current Opinion in Investigational Drugs.
  9. (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.
  10. (April 2005). "NMDA/NR2B selective antagonists in the treatment of ischemic brain injury". Current Drug Targets. CNS and Neurological Disorders.
  11. (December 2005). "The effect of the selective NMDA receptor antagonist traxoprodil in the treatment of traumatic brain injury". Journal of Neurotrauma.
  12. (2002). "Ionotropic Glutamate Receptors as Therapeutic Targets". FP Graham Publishing Co., Johnson City, TN.
  13. (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.
  14. (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.
  15. (2017). "New targets for rapid antidepressant action". Prog. Neurobiol..
  16. "Traxoprodil".
Info: Wikipedia Source

This article was imported from Wikipedia and is available under the Creative Commons Attribution-ShareAlike 4.0 License. Content has been adapted to SurfDoc format. Original contributors can be found on the article history page.

4-phenylpiperidines analgesics antidepressants antiparkinsonian-agents beta-hydroxyamphetamines nmda-receptor-antagonists 4-hydroxyphenyl-compounds
Want to explore this topic further?

Ask Mako anything about Traxoprodil — get instant answers, deeper analysis, and related topics.

Research with Mako

Free with your Surf account

Content sourced from Wikipedia, available under CC BY-SA 4.0.

This content may have been generated or modified by AI. CloudSurf Software LLC is not responsible for the accuracy, completeness, or reliability of AI-generated content. Always verify important information from primary sources.

Report