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KELLY, JP et al.
Journal Of Affective Disorders
The effect of treatment with a new antidepressant, INN 00835, on platelet serotonin uptake in depressed patients
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depression platelets serotonin uptake 5HT UPTAKE BINDING
Background: INN 00835 (4-fluoro-L-phenylalanyl-trans-4-hydroxy-L-prolyl-L-arginyl-glycyl-tryptophanamide ditrifluoroacetate) is a synthetic pentapeptide antidepressant with a potential for rapid onset of action, We were interested to see if such action could be correlated with serotonin uptake by platelets. Methods: In a phase II clinical trial, unipolar depressed patients were administered active drug, INN 00835 or placebo, subcutaneously, at 0.2 mg/kg, once daily for 5 consecutive days, Efficacy of treatment was evaluated by psychometric tests (HAMD, MADS, CSRS, CGI and total VAS). Changes in platelet uptake rates of serotonin (H-3-5HT) were measured in plasma from the patients participating in the phase II clinical trial, prior to and immediately after treatment with INN 00835 (19 patients) or placebo (16 patients), to evaluate the effect of treatment with INN 00835 on the rate of platelet 5-HT uptake. Results: The data evaluated by using the psychometric tests indicated a significant response to treatment with INN 00835 after 5 days of dosing. The rates of platelet 5-HT uptake were lower prior to treatment (baseline), and increased after the 5-day treatment period. The change in the uptake rate (Delta V-max) following treatment was significantly larger in the active group than in the placebo group (P < 0.05), The difference between the placebo group and the patients who responded to treatment was even larger. Limitations: Small number of subjects. Conclusion: The data tend to substantiate the use of platelet serotonin uptake as a biochemical marker of effective treatment of depression. (C) 1999 Elsevier Science B.V. All rights reserved.
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