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Effects of anpirtoline on regional serotonin synthesis in the rat brain: an autoradiographic study.

Anpirtoline has been described as an agonist at 5-HT(1B) receptors with a relatively high potency. It also acts as an agonist at 5-HT(1A) receptors, but has a lower potency than at the 5-HT(1B) 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-[(14)C]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-HT(1B) 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-HT(1A) and/or 5-HT(1B) agonistic properties.[1]

References

  1. Effects of anpirtoline on regional serotonin synthesis in the rat brain: an autoradiographic study. Watanabe, A., Nakai, A., Tohyama, Y., Nguyen, K.Q., Diksic, M. Nucl. Med. Biol. (2006) [Pubmed]
 
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