Effect of dotarizine on K(+)-stimulated [3H]-serotonin and [3H]-acetylcholine release from rat hippocampus.
1. The effect of the diphenylmethyl-piperazine derivative dotarizine on K(+)-stimulated release of [3H]serotonin ([3H]5-HT) and [3H]acethylcholine ([3H]Ach) in rat hippocampal slices was studied. 2. Dotarizine at a concentration of 10(-6) M significantly decreased the basal [3H]5-HT release and, at a concentration of 10(-5) M, it significantly decreased the K(+)-stimulated [3H]5-HT release compared to vehicle controls. 3. Dotarizine, at a concentration of 5 x 10(-7) M, significantly increased both basal and K(+)-stimulated [3H]Ach release. At higher concentrations (10(-6) and 2 x 10(-6) M), dotarizine did not change the basal release but significantly increased the K(+)-stimulated [3H]Ach release. The effect of dotarizine on K(+)-stimulated [3H]Ach release decreased with increasing dotarizine concentrations. 4. It is speculated that, in addition to its Ca2+ antagonistic activity, dotarizine exerts an antagonistic effect on the presynaptic 5-HT autoreceptors, which could account for the facilitation of [3H]Ach release.
Hadjiivanova
C
C
Institute of Physiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
Petkov
V D
VD
Maslarov
D
D
Totev
A
A
Panova
Y
Y
Belcheva
I
I
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D001559:Benzhydryl Compounds; D010879:Piperazines; D012702:Serotonin Antagonists; D012701:Serotonin; C083946:dotarizine; D000109:Acetylcholine; D011188:Potassium