Mechanisms by which quipazine,a putative serotonin receptor agonist,alters brain 5-hydroxyindole metabolism |
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Authors: | JH Jacoby RA Howd MS Levin RJ Wurtman |
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Institution: | Laboratory of Neuroendocrine Regulation, Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, MA 02139 USA |
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Abstract: | Quipazine (2-1-piperazinyl] quinoline maleate) was shown to increase serotonin and decrease 5-hydroxyindoleacetic acid concentrations in whole brain, several brain regions, and the spinal cord of rats 1 hr after its administration (10 mg/kg, i.p.). In animals with transected spinal cords, quipazine induced stronger activation of extensor reflexes than 5-hydroxytryptophan, chlorimipramine, or Lilly 110140. This response could be blocked by methiothepin. In slices of rat cerebral cortex, quipazine inhibited the uptakes of 3H]-serotonin (EC50 = 10?6 M) and 3H]-norepinephrine (); it was equipotent with Lilly 110140 in inhibiting serotonin uptake, but less potent than chlorimipramine (). Quipazine administration to rats did not inhibit monoamine oxidase activity, and actually elevated brain tryptophan levels. These observations suggest that the effects of quipazine on brain serotonin and 5-hydroxyindoleacetic acid concentrations could have been caused by direct activation of central serotonin receptors (which would secondarily decrease impulse flow along serotonergic neurones), or by the inhibition of serotonin reuptake, or by both mechanisms. |
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Keywords: | Please send reprint requests to: Dr R J Wurtman 56-245 Massachusetts Institute of Technology Cambridge MA |
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