A new modification for studying 5-HT uptake by blood platelets: a re-evaluation of tricyclic antidepressants as uptake inhibitors

Abstract

Abstract The effect of imipramine and other antidepressive drugs on 5-HT uptake by rabbit platelets was re-evaluated, since it had become obvious that, in previous studies, too high substrate concentrations and too long incubation times had been used. A Km of 1·8 times 10−7m was obtained for 5-HT uptake when 1 min incubation in plasma was used. Imipramine caused a half-maximal inhibition at 10−7m or lower concentration. When the platelet-rich plasma was diluted with buffer solution, only about 2 times 10−8m imipramine was required for 50% inhibition. This concentration is only 1/500 to 1/100 of concentrations described in most earlier data. In this study, other tricyclic drugs and phenothiazine derivatives were also much more effective than previously demonstrated. Their rank of potency order was, however, very similar to that earlier described. The correlation of uptake inhibition in platelets with 5-HT uptake inhibition in brain synaptosomes was found to be highly significant. It is concluded that the previous studies give valuable information on the relative potency of different drugs inhibiting 5-HT uptake. When the technique is modified as suggested by the present results, the level of uptake-inhibiting potency in an absolute sense is close to that described for other tissues, especially brain synaptosomes or slices. Therefore, platelets can more reliably be used as an easily obtainable model for nerve endings in uptake studies.