nemifitide-ditriflutate and Depressive-Disorder

This study was designed to determine the safety, efficacy and pharmacokinetics of the antidepressant netamiftide (previously designated name: INN 00835) after 5 or 10 daily doses administered to patients diagnosed with major depression. Netamiftide was administered subcutaneously at a fixed dose of 18 mg/patient per day. Of the 55 enrolled patients, 22 were dosed for 10 days with drug, 11 for 5 days with drug followed by 5 days with placebo and 22 for 10 days with placebo only. The effect of treatment with netamiftide was evaluated by the following psychometric tests: Hamilton Depression Rating, Montgomery-Asberg Depression Rating Scale, Carroll Self-Rating Depression and Clinical Global Impression scales. None of the patients experienced significant adverse effects. A pharmacodynamic correlation (P < 0.05) was found between plasma drug concentrations and response to treatment. Highest plasma concentrations (Cmax) of netamiftide averaging 45.7 ng/ml were observed at 0.25 h after dosing. There were 89% responders in the group with Cmax > or = 45.7 ng/ml (minimum therapeutic concentration) versus 40% in the group with Cmax < 45.7 ng/ml. Onset of action was observed within 48 h after treatment, peak effect was observed at approximately 1 week after treatment and efficacy lasted during a 4-week follow-up period. Netamiftide is a promising antidepressant with rapid onset of action and with an excellent safety profile.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Depressive Disorder; Double-Blind Method; Female; Humans; Male; Middle Aged; Oligopeptides; Outpatients; Pilot Projects; Psychiatric Status Rating Scales

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.. 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.. 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.. Small number of subjects.. The data tend to substantiate the use of platelet serotonin uptake as a biochemical marker of effective treatment of depression.

Topics: Adult; Antidepressive Agents; Blood Platelets; Depressive Disorder; Double-Blind Method; Humans; Injections, Subcutaneous; Oligopeptides; Psychometrics; Serotonin; Treatment Outcome