Cerebrovascular effects of dotarizine, a piperazine derivative, in the goat - An in vivo and in vitro complementary study

The effects of dotarizine (1-(diphenylmethyl)-4-[3-(2-phenyl-1, 3-dioxolan- 2-yl)propyl]-piperazine. CAS 84625-59-2) on the cerebral circulation of goa ts were assessed in vivo by recording continuously global cerebral blood no w (gCBF) and cortical perfusion (CP), and in vitro by recording isometric t ension in goat isolated middle cerebral artery (MCA). Administration of dot arizine (1 mu g-5 mg) directly into the cerebroarterial supply of goats pro duced transient increases in gCBF and CP, and decreases in cerebral vascula r resistance (CVR) which were significant for the highest doses tested: 1, 3 and 5 mg. On the other hand, cumulative addition of increasing concentrat ions of dotarizine (10(-8)-3 x 10(-5) mol/l) to MCA segments subjected to t he resting tone of 1 g did not induce sizeable changes in vascular tension; by contrast, dotarizine elicited concentration-dependent relaxations of MC A segments subjected to the active tone induced by either 5-hydroxytryptami ne (10(-6) mol/l) or high-K+ medium (50 mmol/l). These results show that do tarizine exerts a direct relaxant action on cerebral arteries, which result s in an improvement of cerebral perfusion.