Regional differences of cerebrovascular reactivity effected by calcium channel blocker - dotarizine.
Dotarizine, a novel antimigraine prophylactic drug, is chemically related to Diphenylbutylpiperazines, which are known to have Ca(2+)-antagonistic, alpha-adrenolytic and antihistaminic properties. Additionally, Dotarizine exhibits strong 5-HT2 receptor-specific antiserotoninergic properties. The vasostabilizing effect of Dotarizine on cerebrovascular reactivity during different ventilation conditions was demonstrated in various in vitro and in vivo studies. In the presented study, the effect of chronic oral administration of the drug on vascular reactions of different areas of cerebral vessels following hyperventilation was investigated. The experiments were carried out on two groups of experimental animals (rabbits). In the first group (6) 25 mg/kg of Dotarizine dissolved in 0.25% agar was administered orally for 5 days twice daily. The control group of animals (6) was fed with agar of the same concentration according to the same time schedule. During the experiment, 15 min hyperventilation was performed and blood flow velocity (BFV) in the middle cerebral artery (MCA) and the basilar artery (BA) was recorded using Transcranial Doppler apparatus (TCD) before and after hyperventilation state. The obtained results revealed a strong antivasoconstrictive effect of Dotarizine on cerebral vessels reactivity during hyperventilation. In the control experimental group, the 15 min hyperventilation caused a decrease in the mean BFV in MCA and BA by 36 and 14%, respectively, and in the drug-treated group under the same ventilation conditions the decrease of the mean BFV in BA was only 6% and even a slight increase (8% as compared with control values) of BFV in MCA was observed. Comparison of the pulsatility index (PI) values demonstrated a significant decrease of vascular resistance in MCA in the Dotarizine-treated group of animals (P<0.1). From the obtained results it can be concluded that chronic oral administration of a novel compound (Dotarizine) diminishes the vasoconstrictive effect of hyperventilation on cerebral vessels in rabbits. The influence of this drug demonstrates regional differences in the cerebrovascular reactivity and it appears to change the vascular resistance in the small arteries of the cerebrovascular system. Thus, it can be recommended as a good prophylactic antimigraine compound due its vasostabilizing properties.
Kuridze
N
N
Department of Neurosurgery, Medical Research Center, Polish Academy of Sciences, Warsaw, Poland.
Czernicki
Z
Z
Jarus-Dziedzic
K
K
Jurkiewicz
J
J
Cervos-Navarro
J
J
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000378:metabolism; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D006985:Hyperventilation / Q000150:complications / Q000503:physiopathology; D008297:Male; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000378:metabolism; D008881:Migraine Disorders / Q000188:drug therapy* / Q000503:physiopathology; D010879:Piperazines / Q000494:pharmacology*; D011817:Rabbits
D001559:Benzhydryl Compounds; D002121:Calcium Channel Blockers; D010879:Piperazines; C083946:dotarizine