PT  - JOURNAL ARTICLE
AU  - J H Jacoby
AU  - H Shabshelowitz
AU  - J D Fernstrom
AU  - R J Wurtman
TI  - The mechanism by which methiothepin, a putative serotonin receptor antagonist, icnreses brain 5-hydroxyindole levels.
DP  - 1975 Nov 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 257--264
VI  - 195
IP  - 2
4099  - http://jpet.aspetjournals.org/content/195/2/257.short
4100  - http://jpet.aspetjournals.org/content/195/2/257.full
SO  - J Pharmacol Exp Ther1975 Nov 01; 195
AB  - 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.