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UK-315716/UK-240455. Pfizer.

A M Capelli¹, F Micheli

¹GlaxoSmithKline, Medicines Research Centre, Chemistry Dept, Verona, Italy.

Current Opinion in Investigational Drugs (London, England : 2000)

|March 15, 2002

Summary

Pfizer is developing novel NMDA/glycine antagonists for stroke treatment. UK-315716 shows improved efficacy and solubility over UK-240455, suggesting a lower clinical dose for stroke therapy.

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Area of Science:

Neuroscience
Pharmacology

Background:

Stroke is a leading cause of death and disability worldwide.
NMDA/glycine receptors are implicated in excitotoxicity following ischemic stroke.
Developing neuroprotective agents targeting these receptors is a key therapeutic strategy.

Purpose of the Study:

To evaluate the potential of atropoisomeric quinoxalinediones, UK-315716 and UK-240455, as treatments for stroke.
To compare the pharmacological properties and clinical potential of UK-315716 and UK-240455.

Main Methods:

Pfizer is developing UK-315716 and UK-240455, novel NMDA/glycine antagonists.
Both compounds are currently undergoing clinical trials for stroke treatment.
Comparative analysis of aqueous solubility, in vivo efficacy, and projected clinical dosage.

Main Results:

UK-315716 demonstrates superior aqueous solubility compared to UK-240455.
UK-315716 exhibits enhanced in vivo efficacy in preclinical models.
Projected clinical dose for UK-315716 is 200 mg, significantly lower than the 500 mg for UK-240455.

Conclusions:

UK-315716 represents a promising advancement over UK-240455 for stroke therapy.
The improved properties of UK-315716 may lead to a more effective and convenient treatment regimen.
Further clinical evaluation is warranted to confirm the therapeutic benefits of UK-315716 in stroke patients.

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