title: The calmodulin antagonist trifluoperazine provides mild prophylactic protection against cerebral vasospasm after subarachnoid hemorrhage, but no therapeutic value.
abstract: In vitro studies of the canine basilar artery have demonstrated that calmodulin antagonism can effectively inhibit cerebral arterial smooth muscle contractility. The prophylactic and therapeutic effectiveness of a potent calmodulin antagonist, the phenothiazine compound trifluoperazine (TFP), was investigated in vivo over a wide range of doses in the well-documented "double-subarachnoid hemorrhage" canine model of cerebral vasospasm. The compound is perhaps more well-known under its trade name, Stelazine, as a classic antipsychotic drug. The drug demonstrated no therapeutic relief of preexisting chronic cerebral vasospasm at any time during 2 days of systemic administration at any practical dose. At doses far in excess of the normally accepted therapeutic range in humans, a prophylactic regimen reduced the severity of chronic cerebral vasospasm after subarachnoid hemorrhage by approximately 35% compared to untreated dogs.
authors.affiliation: Laboratory for Cerebrovascular Biophysics, Neurosurgical Service, Massachusetts General Hospital, Boston.
authors.forename: J W
authors.initials: JW
authors.lastname: Peterson
authors.forename: G
authors.initials: G
authors.lastname: Candia
authors.forename: A J
authors.initials: AJ
authors.lastname: Spanos
authors.forename: N T
authors.initials: NT
authors.lastname: Zervas
mesh_terms: D000818:Animals; D004285:Dogs; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D014268:Trifluoperazine / Q000627:therapeutic use*
chemical_list: D014268:Trifluoperazine