title: Effects of anpirtoline on regional serotonin synthesis in the rat brain: an autoradiographic study.
abstract: Anpirtoline has been described as an agonist at 5-HT1B receptors with a relatively high potency. It also acts as an agonist at 5-HT1A receptors, but has a lower potency than at the 5-HT1B sites. There is very little known about the mechanism by which anpirtoline influences regional 5-HT synthesis. The aim of the present study was to investigate the effects of acutely and chronically administered anpirtoline on 5-HT synthesis in the rat brain using the autoradiographic alpha-[14C]methyl-L-tryptophan method. In the acute study, anpirtoline (2.0 mg/kg) was administered intraperitoneally 30 min before the tracer injection. The control rats were injected with the same volume of saline. In the chronic study, anpirtoline (2 mg/kg per day) was injected subcutaneously in saline once a day for 10 days. There were no significant differences between the plasma-free and total tryptophan concentrations between the anpirtoline treatment and the respective control groups. In the acute experiment, 5-HT synthesis rates in all of the brain areas investigated were significantly decreased by anpirtoline when compared to the saline-treated group. In the chronic anpirtoline experiment, 5-HT synthesis rates of almost all of the projection areas, as well as the raphe nuclei, were normalized or had a tendency to be normalized. These results suggest that it is likely that the terminal 5-HT1B receptors are involved in the regulation of 5-HT synthesis in the projection areas and that 5-HT synthesis, in the raphe, is likely influenced by anpirtoline's 5-HT1A and/or 5-HT1B agonistic properties.
authors.affiliation: Cone Neurological Research Laboratory, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A 2B4.
authors.forename: Arata
authors.initials: A
authors.lastname: Watanabe
authors.forename: Akio
authors.initials: A
authors.lastname: Nakai
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Tohyama
authors.forename: Khnah Q
authors.initials: KQ
authors.lastname: Nguyen
authors.forename: Mirko
authors.initials: M
authors.lastname: Diksic
mesh_terms: D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000096:biosynthesis*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
chemical_list: D010880:Piperidines; D011725:Pyridines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C075631:anpirtoline; D012701:Serotonin