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.