Uptake of 5-hydroxytryptamine by blood platelets incubated in plasma from rats and humans treated with amitriptyline and imipramine.

Blood platelets and [3H]-5HT ([3H]-5-hydroxytryptamine) were incubated in plasma samples taken from rats and humans treated with tricyclic antidepressants. The inhibition of 5-HT uptake detected in plasma was used as a bioassay of the drug concentration, and this was compared with gas chromatographic (GC) measurements of the same samples. With rats 5-HT uptake inhibition in plasma was studied one hour after five different doses of imipramine or amitriptyline i.p., and the time-course of uptake inhibition was studied from plasma samples taken 1, 2, 3 and 6 hours after injecting 10 mg/kg imipramine in to rats. Under long-term treatment, uptake inhibition was studied in samples taken from 20 patients treated with amitriptyline for 2 weeks or longer. In the samples with tricyclics, within the therapeutic range as detected by GC, the uptake inhibition was well over 50%. Bioassay based on uptake inhibition gave higher apparent results than did GC. The demethylated derivatives of the tricyclics, which were also measured by GC, did not explain the discrepancy. Thus, it is possible that other active metabolites formed in vivo also contribute to uptake inhibition.