MECHANISMS BY WHICH METHIOTHEPIN, A PUTATIVE SEROTONIN RECEPTOR ANTAGONIST, INCREASES BRAIN 5-HYDROXYINDOLE LEVELS

  • 1 January 1975
    • journal article
    • research article
    • Vol. 195  (2) , 257-264
Abstract
Brain tryptophan and 5-hydroxyindole levels are elevated in rats given methiothepin [(1-[10,11-dihydro-8-(methylthio).ltbbrac.b,f.rtbbrac.thiepin-10,41]-4-methylpiperazine maleate], a neuroleptic that appears to block serotin receptors. The rise of brain tryptophan probably results from a drug-induced increase in the ratio of plasma tryptophan concentration to the sum of the neutral amino acids in plasma that compete with tryptophan for uptake into the brain; this change in the plasma amino acid pattern may be mediated in part by a methiothepin-induced rise in plasma insulin. Methiothepin also decreases the proportion of circulating tryptophan bound to albumin. Unlike exogenous tryptophan methiothepin fails to increase 5-hydroxyindoles caudal to the site of a spinal cord transection. The mechanism by which methiothepin elevates 5-hydroxyindole levels may involve not only increased brain tryptophan levels but also continued impulse flow along serotonergic neurons.

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