title: The effect of treatment with a new antidepressant, INN 00835, on platelet serotonin uptake in depressed patients.
abstract: BACKGROUND
  INN 00835 (4-fluoro-L-phenylalanyl-trans-4-hydroxy-L-prolyl-L-arginyl-glycyl-trypt ophanamide 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 (3H-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 (deltaVmax) 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.
  
  
  CONCLUSIONS
  Small number of subjects.
  
  
  CONCLUSIONS
  The data tend to substantiate the use of platelet serotonin uptake as a biochemical marker of effective treatment of depression.
authors.affiliation: Department of Pharmacology, University College, Galway, Ireland.
authors.forename: J P
authors.initials: JP
authors.lastname: Kelly
authors.forename: G
authors.initials: G
authors.lastname: Nicolau
authors.forename: A
authors.initials: A
authors.lastname: Redmond
authors.forename: B E
authors.initials: BE
authors.lastname: Leonard
authors.forename: J
authors.initials: J
authors.lastname: Noble
authors.forename: L
authors.initials: L
authors.lastname: Sverdlov
authors.forename: R
authors.initials: R
authors.lastname: Molinar
authors.forename: A J
authors.initials: AJ
authors.lastname: Kastin
authors.forename: R H
authors.initials: RH
authors.lastname: Ehrensing
authors.forename: J P
authors.initials: JP
authors.lastname: Feighner
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001792:Blood Platelets / Q000502:physiology; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D006801:Humans; D007279:Injections, Subcutaneous; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use*; D011594:Psychometrics; D012701:Serotonin / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D009842:Oligopeptides; C406668:nemifitide ditriflutate; D012701:Serotonin