The mechanism by which methiothepin, a putative serotonin receptor antagonist, icnreses brain 5-hydroxyindole levels.
Brain tryptophan and 5-hydroxyindole levels are elevated in rats given methiothepin, a neuroleptic that appears to block serotonin receptors. The rise in 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 that is bound to albumin. Unlike exogenous tryptophan, methiothepin fails to increase 5-hydroxyin-doles caudal to the site of a spinal cord transection. Therefore, the mechanism by which methiothepin elevates 5-hydroxyindole levels involves not only increased brain tryptophan levels but also continued impulse flow along serotonergic neurons.
D000596:Amino Acids / Q000097:blood; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003988:Dibenzothiepins / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007328:Insulin / Q000097:blood; D008297:Male; D008719:Methiothepin / Q000494:pharmacology*; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D013116:Spinal Cord / Q000502:physiology; D014364:Tryptophan / Q000378:metabolism*
D000596:Amino Acids; D003988:Dibenzothiepins; D007328:Insulin; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D008719:Methiothepin; D014364:Tryptophan