Related Experiment Videos
Lazaroids. CNS pharmacology and current research
W M Clark1, J S Hazel, B M Coull
1Department of Neurology, Oregon Health Sciences University, Portland, USA.
Drugs
|December 1, 1995
Summary
Tirilazad, a 21-aminosteroid, shows promise as an oxygen free radical scavenger for central nervous system disorders. While effective in preclinical models of spinal cord and head injuries, clinical efficacy is limited by drug concentration issues, except for subarachnoid hemorrhage.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- 21-aminosteroids, known as lazaroids, are potent inhibitors of lipid peroxidation and function as oxygen free radical scavengers.
- The lazaroid tirilazad mesylate has been investigated for therapeutic applications in various central nervous system (CNS) disorders.
- Preclinical studies indicate significant benefits of tirilazad in models of spinal cord trauma and head injury.
Purpose of the Study:
- To evaluate the therapeutic potential of tirilazad mesylate in CNS disorders, including spinal cord injury, head injury, subarachnoid hemorrhage, and stroke.
- To investigate the efficacy of tirilazad in preclinical models and clinical settings.
- To identify factors influencing tirilazad's clinical effectiveness, such as achieving adequate drug concentrations.
Main Methods:
- Utilizing tirilazad in preclinical models of spinal cord trauma, head injury, subarachnoid hemorrhage, and stroke.
- Conducting clinical studies to assess tirilazad's efficacy and safety in patients with these neurological conditions.
- Analyzing drug concentrations achieved in clinical trials to correlate with therapeutic outcomes.
Main Results:
- Tirilazad demonstrated significant benefits in experimental models of spinal cord trauma, head injury, and stroke.
- Clinical studies for head injury and stroke have not confirmed preclinical efficacy, potentially due to insufficient drug concentrations.
- Clinical trials for subarachnoid hemorrhage showed promising results, with tirilazad reducing vasospasm and cerebral infarction, leading to approval in several European countries.
Conclusions:
- Tirilazad mesylate exhibits neuroprotective properties and is beneficial in specific CNS injury models.
- Clinical success with tirilazad is contingent upon achieving adequate therapeutic drug concentrations.
- Tirilazad is a promising therapeutic agent for subarachnoid hemorrhage, with ongoing evaluation for other CNS disorders.