Summary
Since quipazine is a potent 5-HT agonist in peripheral organs, its possible stimulatory effects on serotoninergic receptors in the rat brain were investigated. Quipazine administration (10 mg/kg, i.p.) induced a significant decrease in the synthesis and turnover rates of serotonin in the brain stem as well as in the forebrain. It is not likely that these changes were mediated by a negative feed-back mechanism triggered by adirect action of quipazine on central 5-HT postsynaptic receptors. Indeed, in contrast to LSD and 5-methoxy-N,N-dimethyltryptamine, this compound failed to activate the 5-HT sensitive adenylate cyclase in colliculi homogenates of newborn rats. However, quipazine exerted direct effects on serotoninergic terminals. It inhibited competitively the reuptake process in synaptosomes (Ki =1.38×10−7 M) and stimulated the K+ evoked release of newly synthesized3H-5-HT in slices of the brain stem. Injected in vivo in a dose which affected 5-HT uptake and release, quipazine did not modify MAO activity. However, this activity was noncompetitively inhibited by high concentration of the drug in vitro (Ki=3.0×10−5 M). These actions are very likelyindirectly responsible for the stimulation of central 5-HT receptors.
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Hamon, M., Bourgoin, S., Enjalbert, A. et al. The effects of quipazine on 5-HT metabolism in the rat brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 294, 99–108 (1976). https://doi.org/10.1007/BF00692790
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DOI: https://doi.org/10.1007/BF00692790