5-HT2A receptor antagonist M100907 reduces serotonin synthesis: an autoradiographic study.

The effects of the administration of the serotonin (5-HT)(2A) antagonist, M100907, on 5-HT synthesis rates, were evaluated using the α-[(14)C]methyl-l-tryptophan (α-MTrp) autoradiographic method. In the treatment study, M100907 (10mg/kg) was injected intraperitoneally 30 min before the α-MTrp injection (30 μCi over 2 min). A single dose of M100907 caused a significant decrease in the synthesis in the anterior olfactory nucleus, accumbens nucleus, frontal cortex, sensory-motor cortex, cingulate cortex, medial caudate-putamen, dorsal thalamus, substantia nigra, inferior collicus, raphe magnus nucleus, superior olive, and raphe pallidus nucleus. These data suggest that the terminal 5-HT(2A) receptors are involved in the regulation of 5-HT synthesis in the entire brain. Further, 5-HT synthesis is likely regulated by the 5-HT(2A) antagonistic property of M100907 in the cortices, anterior olfactory nucleus, caudate putamen, and nucleus accumbens.