, Volume 100, Issue 4, pp 470–476 | Cite as

[3H] sertraline binding to rat brain membranes

  • B. K. Koe
  • L. A. Lebel
  • W. M. Welch
Original Investigations


Tritiated sertraline, a radiolabeled form of a potent and selective inhibitor of serotonin uptake, was found to bind with high affinity to rat whole brain membranes. Characterization studies showed that [3H] sertraline binding occurred at a single site with the following parameters:K d 0.57 nM,Bmax 821 fmol/mg protein,n h 1.06. This binding was reversible; the dissociation constant calculated from kinetic measurements (K d 0.81 nM) agreed with that determined by saturation binding experiments. [3H] Sertraline binding in the presence of serotonin, paroxetine, fluoxetine or imipramine suggested competitive inhibition of binding (large increase inK d with little change inBmax). The rank order of potency of inhibition of [3H] sertraline binding was similar to that of inhibition of serotonin uptake for known uptake inhibitors and the 1-amino-4-phenyltetralin uptake blockers. A marked decrease in ex vivo [3H] sertraline binding in the brain of rats 7 days after treatment withp-chloroamphetamine was consistent with the loss of serotonin uptake sites induced by this agent. The results of our study indicated that [3H] sertraline labels serotonin uptake sites in rat brain.

Key words

[3H] Sertraline binding Serotonin uptake Uptake blockers 1-Amino-4-phenyltetralins 


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Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • B. K. Koe
    • 1
  • L. A. Lebel
    • 1
  • W. M. Welch
    • 1
  1. 1.Central Research Division, Pfizer Inc.GrotonUSA

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