Phenothiazines reduce ischemic damage to the central nervous system.
We found substantial alterations in reactions catalyzed by calcium/phospholipid-dependent and calcium/calmodulin-dependent protein kinases during CNS ischemia which suggested that phenothiazines, drugs capable of inhibiting these reactions, might reduce neurologic damage. To test this hypothesis, we used chlorpromazine and trifluoperazine. Both drugs reduced neurologic function deficits relative to controls in a rabbit multiple cerebral embolism model and a rabbit spinal cord ischemia model. Chlorpromazine was effective despite reduction of blood pressure, and trifluoperazine did not alter blood pressure. These findings suggest that phenothiazines may be useful for preserving neurologic function when administered shortly after the onset of CNS ischemia.
Zivin
J A
JA
Department of Neurology, Veterans Administration Medical Center, San Diego, CA.
Kochhar
A
A
Saitoh
T
T
D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D002746:Chlorpromazine / Q000627:therapeutic use*; D007511:Ischemia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D010640:Phenothiazines / Q000627:therapeutic use*; D011817:Rabbits; D013116:Spinal Cord / Q000098:blood supply* / Q000187:drug effects / Q000503:physiopathology; D014268:Trifluoperazine / Q000627:therapeutic use*
D010640:Phenothiazines; D014268:Trifluoperazine; D002746:Chlorpromazine