Serotonin-releasing effects of substituted piperazines in vitro.
The effects of various piperazine-containing compounds on the release of endogenous serotonin (5-HT) from rat hypothalamic slices were evaluated. Incubation of hypothalamic slices with m-chlorophenylpiperazine ( mCPP ) or m- trifluoromethylphenylpiperazine ( mTFMPP ) evoked a potent, dose-dependent release of endogenous 5-HT that was similar in magnitude to that seen with tryptamine, p-chloroamphetamine, or fenfluramine. In the presence of the 5-HT uptake blockers fluoxetine or chlorimipramine, this release was reduced dramatically. Furthermore, removal of calcium from the incubation medium had little effect on the drug-induced release, suggesting that the release mechanism involved displacement of 5-HT stores and not depolarization-induced exocytosis. Trazodone, MK-212, and quipazine had only small effects on release. These studies show that several piperazine-containing compounds can evoke a potent release of endogenous stores of hypothalamic 5-HT in vitro, actions which should be considered together with their direct agonist activity when interpreting the CNS effects in vivo.
D000818:Animals; D005473:Fluoxetine / Q000494:pharmacology; D007031:Hypothalamus / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*; D010133:p-Chloroamphetamine / Q000494:pharmacology
D010879:Piperazines; D011985:Receptors, Serotonin; D005473:Fluoxetine; C018406:1-(3-trifluoromethylphenyl)piperazine; D012701:Serotonin; D010133:p-Chloroamphetamine; C015068:1-(3-chlorophenyl)piperazine