Behavioral effects of the Ca2+/5-HT antagonist dotarizine

The diphenyl-methyl-piperazine derivatives with Ca(2+)-antagonistic effect dotarizine (DOT), Fl-6020 and flunarizine were investigated in experiments on rats. The substances tested were administered repeatedly at an oral dose of 50 mg/kg. Behavioral methods were used to study the exploratory activity when the animals were placed in an environment that was unfamiliar to them (the chamber of the Opto Varimex apparatus), the elevated plus-maze method for examining the effect on anxiety, and the method of recording changes in motor activity (using the Automex II apparatus). DOT was found to increase motor activity and to have an anxiolytic effect. Combination of DOT--a compound with Ca(2+)--and 5-HT2-receptor antagonistic action--and the 5-HT-receptor agonists and antagonists used (buspirone, NAN190, pindolol, ritanserin and ondansetron) resulted in such changes in the development of habituation and in anxiety, which suggest that the modulating effects of DOT depend but partly on its typical interaction with the 5-HT2 receptor. Apparently, the Ca(2+)-antagonistic action of DOT plays a definite role, changing its biological activity depending on the 5-HT receptor subtype at the level of which the interaction is taking place.