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CP-101606 Pfizer Inc.

P L Chazot1

  • 1University of Sunderland, School of Sciences, Wharncliffe Street, Sunderland, Tyne and Wear, SR2 3SD, UK. Paul.Chazot@sunderland.ac.uk

Current Opinion in Investigational Drugs (London, England : 2000)
|March 16, 2001
PubMed
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CP-101606, a novel neuroprotectant, shows promise in treating head injuries by selectively blocking NMDA receptors. Early trials indicate good tolerability and potential for patient recovery, avoiding common side effects.

Area of Science:

  • Neuroscience
  • Pharmacology

Background:

  • The N-methyl-D-aspartate (NMDA) receptor, particularly the NR2B subunit, is implicated in neuronal damage following injury.
  • Developing neuroprotective agents that target specific NMDA receptor subunits is crucial for treating conditions like head trauma and neurodegenerative diseases.

Purpose of the Study:

  • To evaluate the safety, tolerability, and efficacy of CP-101606 as a neuroprotectant.
  • To investigate the mechanism of action and receptor selectivity of CP-101606.

Main Methods:

  • Phase I and II clinical trials in the US and Japan for head injury.
  • Open-label study in patients with severe head trauma.
  • In vitro studies using cultured hippocampal and cerebellar neurons to assess glutamate-induced toxicity.

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Main Results:

  • CP-101606 was well tolerated with a good safety profile in Phase I trials.
  • 80% of patients with severe head trauma showed good recovery at 3 months post-treatment.
  • CP-101606 demonstrated potent, selective inhibition of NMDA receptor-mediated neurotoxicity in hippocampal neurons, with IC50 values of 11 and 35 nM.

Conclusions:

  • CP-101606 is a potent and selective NMDA receptor antagonist with potential neuroprotective properties.
  • Its NR2B subunit selectivity and lack of amnesic side effects differentiate it from other NMDA receptor antagonists.
  • Further clinical development is warranted for the treatment of head injury and potentially other neurological conditions.