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 (delta CRF: -3 +/- 2 pg/ml) and a significant 14% fall in the CRF concentrations of the eight subjects who received 100 mg DMI (delta CRF: -8 +/- 3 pg/ml). The mean CSF concentration of CRF was unchanged in the six subjects randomized to placebo (delta 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.
Veith
R C
RC
Geriatric Research, Education, and Clinical Center (GRECC), Department of Veterans Affairs Medical Center (DVAMC), Seattle, WA 98108.
Lewis
N
N
Langohr
J I
JI
Murburg
M M
MM
Ashleigh
E A
EA
Castillo
S
S
Peskind
E R
ER
Pascualy
M
M
Bissette
G
G
Nemeroff
C B
CB
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000097:blood*; D003891:Desipramine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D009638:Norepinephrine / Q000134:cerebrospinal fluid; D010913:Pituitary-Adrenal System / Q000187:drug effects
D003346:Corticotropin-Releasing Hormone; D003891:Desipramine; D006854:Hydrocortisone; D009638:Norepinephrine