The mechanism by which methiothepin, a putative serotonin receptor antagonist, icnreses brain 5-hydroxyindole levels

JH Jacoby, H Shabshelowitz, JD Fernstrom and RJ Wurtman

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.

Volume 195, Issue 2, pp. 257-264, 11/01/1975
Copyright © 1975 by American Society for Pharmacology and Experimental Therapeutics