title: Human brainstem serotonin receptors: characterization and implications for subcortical myoclonus.
abstract: The immediate serotonin (5-HT) precursor, 5-hydroxy-L-tryptophan (L-5-HTP), is an investigational treatment for myoclonic disorders. Its mechanism of action in humans is incompletely understood. We measured the density of subtypes of 5-HT1 and 5-HT2 receptors and the affinity of 5-HT and L-5-HTP in vitro in the human brainstem and cortex, regions associated with subcortical and cortical myoclonus, respectively. In the cortex, the rank order of 5-HT receptor subtype Bmax was 5-HT2A (low-affinity), 5-HT1A, 5-HT uptake sites, 5-HT1D, 5-HT2C, 5-HT1E/F, and 5-HT2A (high-affinity) sites. In the brainstem, the rank order was 5-HT uptake sites, 5-HT1D, 5-HT2C, 5-HT1A, and 5-HT2A(L) sites. Specific binding at 5-HT1E/F and high-affinity 5-HT2A sites was too low for characterization. In competition studies, 5-HT had high affinity for 5-HT1A and 5-HT2C sites in the brainstem and cortex, but L-5-HTP was > 1,000-fold less active. These data support the hypothesis that in humans L-5-HTP stimulates 5-HT receptors in the CNS only after conversion to 5-HT. They also indicate in the human brainstem a prominence of 5-HT1A sites and paucity of 5-HT1D, 5-HT1E/F, and 5-HT2A sites, which has implications for brainstem-mediated myoclonus and response to serotonergic drugs.
authors.affiliation: Department of Neurology, George Washington University, Washington, D.C., USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Pranzatelli
authors.forename: I
authors.initials: I
authors.lastname: Galvan
authors.forename: P T
authors.initials: PT
authors.lastname: Tailor
mesh_terms: D006916:5-Hydroxytryptophan / Q000378:metabolism; D000328:Adult; D000368:Aged; D001667:Binding, Competitive; D001933:Brain Stem / Q000378:metabolism / Q000648:ultrastructure*; D002540:Cerebral Cortex / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009207:Myoclonus / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000145:classification* / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism
chemical_list: D011985:Receptors, Serotonin; D012701:Serotonin; D006916:5-Hydroxytryptophan