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Paroxetine, a potent selective long-acting inhibitor of synaptosomal 5-HT uptake in mice

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Summary

The high-affinity uptake of tritium labelled tryptophan (TRY), 5-hydroxytryptophan (5-HPT), 5-hydroxytryptamine (5-HT), noradrenaline (NE), dopamine (DA), glycine and glutamic acid into forebrain synaptosomes, and serum 5-HT concentrations were studied in mice.In vitro the rank order of potency (the concentration causing 50 percent uptake inhibition) of seven inhibitors of 5-HT uptake was paroxetine>citalopram≧ femoxetine>fluoxetine>alaproclate≧imipramine>zimelidine. Paroxetine was a weak inhibitor of the NE and DA uptake without any effect on the synaptosomal accumulation of TRY, 5-HTP, glycine or glutamic acid. Dose related inhibition of synaptosomal 5-HT uptakeex vivo was found one hour after intraperitoneal single dose administered paroxetine (ED50=0.3 mg/kg i.p.) and 75% inhibition persisted 24 hours after 10 mg/kg i.p. (=ED100). Chronically administered paroxetine produced a slight decrement of synaptosomal NE uptake. Serum 5-HT concentrations were found dose dependently reduced during chronic paroxetine treatment. A dose level of paroxetine which reduced serum 5-HT concentrations with 50% produced an almost complete inhibition of synaptosomal 5-HT uptake.

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Author notes

  1. I. Magnussen

    Present address: Department of Neurology, Aarhus University Hospital, Aarhus, Denmark

Authors and Affiliations

  1. Department of Neurology, Aarhus University Hospital, Aarhus, Denmark

    Kirsten Tønder & F. Engbaek

  2. The Research Laboratory for Metabolic Disorders, Department of Clinical Chemistry, Aarhus University Hospital, Aarhus, Denmark

    I. Magnussen, Kirsten Tønder & F. Engbaek

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  1. I. Magnussen
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  2. Kirsten Tønder
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  3. F. Engbaek
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Magnussen, I., Tønder, K. & Engbaek, F. Paroxetine, a potent selective long-acting inhibitor of synaptosomal 5-HT uptake in mice. J. Neural Transmission 55, 217–226 (1982). https://doi.org/10.1007/BF01276577

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  • DOI: https://doi.org/10.1007/BF01276577

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