The effect of Dotarizine (Ca2+ channel blocker) on cerebral vessel reactivity in animals subjected to hyperventilation and anoxia.

Abstract

Dotarizine--a novel piperazine derivative--belongs to wide spectrum Ca+ channel antagonists. It was reported to have strong vasodilatory and antiserotoninergic activities. Unlike other Ca+ channel blockers Dotarizine was found to have lower oral toxicity. In the presented study the influence of the oral administration of the novel compound on the blood flow velocity changes in different cerebral arteries--in basilar artery (BA) and middle cerebral artery (MCA)--was investigated under hyperventilation and hypoxic conditions of rabbits. In the first experimental group 25 mg/kg of Dotarizine dissolved in 0.25% agar was administered orally three times at the 10 hours' intervals. The sham group of animals was fed with agar of the same concentration. The results revealed that oral administration of Dotarizine diminished the vasoconstrictive effect of hyperventilation and this was more pronounced in MCA than in BA. During anoxic conditions stronger vasodilatory effects were observed in both groups of vessels and the low value of pulsatility index (PI) reflected pronounced decrease of the peripheral resistance, in comparison to the control group. Thus, the oral administration of Dotarizine decreases the peripheral resistance of cerebral vessels and therefore seems to have influence on the minute arteries of cerebrovascular system of the brain.