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Phenothiazines reduce ischemic damage to the central nervous system.

J A Zivin¹, A Kochhar, T Saitoh

¹Department of Neurology, Veterans Administration Medical Center, San Diego, CA.

|March 13, 1989

Summary

Phenothiazines may protect the brain and spinal cord from ischemic damage. These drugs, including chlorpromazine and trifluoperazine, reduced neurological deficits in animal models of central nervous system (CNS) ischemia.

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Area of Science:

Neuroscience
Pharmacology

Background:

Central nervous system (CNS) ischemia causes significant alterations in protein kinase activity.
Calcium/phospholipid-dependent and calcium/calmodulin-dependent protein kinases are notably affected during ischemic events.

Purpose of the Study:

To investigate the potential neuroprotective effects of phenothiazines.
To determine if phenothiazines can mitigate neurological damage following CNS ischemia.

Main Methods:

Utilized chlorpromazine and trifluoperazine, known phenothiazine inhibitors.
Employed rabbit models of multiple cerebral embolism and spinal cord ischemia.
Assessed neurological function deficits in treated and control groups.

Main Results:

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Both chlorpromazine and trifluoperazine significantly reduced neurological function deficits in ischemic rabbit models.
Chlorpromazine demonstrated efficacy in reducing deficits even when causing a drop in blood pressure.
Trifluoperazine did not induce changes in blood pressure while still showing protective effects.

Conclusions:

Phenothiazines show promise as therapeutic agents for reducing neurological damage after CNS ischemia.
Early administration of phenothiazines may be a viable strategy for preserving neurological function post-ischemia.