Effect of desipramine on cerebrospinal fluid concentrations of corticotropin-releasing factor in human subjects

To assess the effect of desipramine (DMI) on corticotropin-releasing-factor (CRF) activity in the central nervous system, we measured cerebrospinal fluid (CSF) concentrations of CRF in healthy volunteers following short-term administration of DMI or placebo. DMI administration for 2 days was associated with a significant dose-related reduction in CRF concentrations. There was a nonsignificant 6% reduction in CRF concentrations among the 10 subjects who received 50 mg DMI (△ CRF: -3±2 pg/ml) and a significant 14% fall in the CRF concentrations of the eight subjects who received 100 mg DMI (△ CRF: -8±3 pg/ml). The mean CSF concentration of CRF was unchanged in the six subjects randomized to placebo (△ CRF: 1±5 pg/ml). DMI administration had no effect on CSF norepinephrine concentrations ( n = 24) or on plasma cortisol ( n = 25). We conclude that short-term administration of DMI in healthy volunteers is associated with a dose-related reduction in CSF concentrations of CRF.