Traxoprodil (developmental code name CP-101606) is a drug developed by

Pfizer Pfizer Inc. ( ) is an American Multinational corporation, multinational Pharmaceutical industry, pharmaceutical and biotechnology corporation headquartered at The Spiral (New York City), The Spiral in Manhattan, New York City. Founded in 184 ...

which acts as an

NMDA antagonist NMDA receptor antagonists are a class of drugs that work to antagonize, or inhibit the action of, the ''N''-Methyl-D-aspartate receptor ( NMDAR). They are commonly used as anesthetics for humans and animals; the state of anesthesia they ind ...

, selective for the NR2B subunit. It has neuroprotective,

analgesic An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in s ...

, 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 Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

, but results from

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...

s 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 Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...

effects similar to those of

ketamine Ketamine is a cyclohexanone-derived general anesthetic and NMDA receptor antagonist with analgesic and hallucinogenic properties, used medically for anesthesia, depression, and pain management. Ketamine exists as its S- (esketamine) a ...

, 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

-like rapidly-acting

effects in a small clinical trial of 30 patients with depression who were non-responders to 6 weeks of

paroxetine Paroxetine ( ), sold under the brand name Paxil among others, is an Antidepressant, antidepressant medication of the selective serotonin reuptake inhibitor (SSRI) class used to treat major depressive disorder, obsessive-compulsive disorder, o ...

treatment. The response rate was 60%, relative to 20% for

placebo A placebo ( ) can be roughly defined as a sham medical treatment. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. Placebos are used in randomized clinical trials ...

, 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 Substituted phenethylamines (or simply phenethylamines) are a chemical class of organic compounds that are based upon the phenethylamine structure; the class is composed of all the derivative (chemistry), derivative compounds of phenethylamine ...

and β-hydroxyamphetamine

derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...

References

{{Phenethylamines 4-Phenylpiperidines Analgesics Antidepressants Antiparkinsonian agents Beta-Hydroxyamphetamines NMDA receptor antagonists 4-Hydroxyphenyl compounds

See also

References