The effects of quipazine on 5-HT metabolism in the rat brain.
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 a direct 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 X 10(-7) M) and stimulated the K+ evoked release of newly synthesized 3H-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 non-competitively inhibited by high concentratin of the drug in vitro (Ki=3.0 X 10(-5) M). These actions are very likely indirectly responsible for the stimulation of central 5-HT receptors.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D001933:Brain Stem / Q000378:metabolism; D002997:Clomipramine / Q000494:pharmacology; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D008996:Monoamine Oxidase Inhibitors; D010879:Piperazines / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D011955:Receptors, Drug / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism
D008996:Monoamine Oxidase Inhibitors; D010879:Piperazines; D011804:Quinolines; D011955:Receptors, Drug; D012701:Serotonin; D008238:Lysergic Acid Diethylamide; D000262:Adenylyl Cyclases; D002997:Clomipramine; D011188:Potassium