Vasostabilizing effect of Dotarizine (Ca(2+)-channel blocker) on cerebrovascular reactivity in rabbits

Disturbances of the cerebrovascular reactivity in cases of migraine with aura are well-known. It has been suggested that the vasostabilizing effects of novel prophylactic pharmaceuticals are determined by their antiserotoninergic and/or nitric oxide releasing properties. Dotarizine, a representative of Ca2+ channel blockers from diphenilbutilpiperazines group also reveals antiserotoninergic 5-HT2A and 5-HT2C receptor-specific properties. The vasodilatatory and antivasoconstrictive properties of this compound were reported previously. In this study the efficacy of Dotarizine chronic oral administration on cerebrovascular reactivity during hyperventilation was examined with respect to its duration of action. Experiments were carried out on 13 rabbits. There was an interval of two days between a five days compound administration and performed hyperventilation. Blood flow velocities (BFV) in the middle cerebral artery (MCA) and basilar artery (BA) were measured in control conditions, after 10 min hyperventilation and in the tenth minute of recovery of normoventilation. Our data reveal a decrease of antivasoconstrictive properties of Dotarizine between its administration and vasoconstrictive test. Subsequent normoventilation showed a distinct vasostabilising effect of this compound with evident regional differences in its influence on cerebral vessels. Thus Dotarizine might be useful as prophylactic medication in migraine therapy, due to its Ca2+ channel blocking and antiserotoninergic properties, but the time-frame of its efficacy has to be defined.