The effects of the specific serotonin antagonist ICI 169,369 on the pituitary hormone response to insulin-induced hypoglycaemia in humans.
OBJECTIVE
To examine the role of serotonin in pituitary hormone release by studying the effect of a specific 5HT2 receptor antagonist, ICI 169,369, on the ACTH, prolactin, growth hormone and AVP response to insulin-induced hypoglycaemia in healthy humans.


METHODS
A double-blind, within-subject trial using a crossover design to compare the effect of placebo with two doses of ICI 169,369 on pituitary hormone responses to insulin-induced hypoglycaemia.


METHODS
Ten healthy subjects were studied in the low-dose (30 mg x 2) limb and 11 healthy volunteers in the high-dose (80 mg x 2) limb.


METHODS
Plasma concentrations of prolactin, growth hormone, ACTH, cortisol and AVP, and blood glucose.


RESULTS
In the low-dose study, pretreatment with 30 mg ICI 169,369, 10 and 2 hours before the study, had no effect on the fall in blood glucose or the rise in plasma ACTH, prolactin, growth hormone, AVP or plasma cortisol following insulin injection, when compared with placebo. In the high-dose study the effect of a higher dose (80 mg) of ICI 169,369 on the pituitary hormone response to hypoglycaemia was compared with that of placebo. Although the fall in blood glucose was similar following drug (4.3 +/- 0.1 to 1.5 +/- 0.5 mmol/l, mean +/- SEM, P less than 0.001) and placebo (4.3 +/- 0.1 to 1.4 +/- 0.4 mmol/l, P less than 0.001), the rise in plasma AVP was lower (P less than 0.05) following pretreatment with drug (0.5 +/- 0.2 to 2.1 +/- 0.6 pmol/l, P less than 0.05) than with placebo (0.7 +/- 0.2 to 3.4 +/- 0.9 pmol/l, P less than 0.01).


CONCLUSIONS
The ACTH, prolactin, growth hormone and cortisol responses were unaffected by ICI 169,369. The data are compatible with an inhibitory effect of the serotonin antagonist ICI 169,369 on the AVP, but not the ACTH, prolactin or growth hormone response to insulin-induced hypoglycaemia in humans.
Thompson
C J
CJ
Endocrine Unit, Royal Victoria Infirmary, Newcastle upon Tyne, UK.
Jones
I R
IR
Walker
M
M
Baylis
P H
PH
Kendall-Taylor
P
P
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000328:Adult; D001127:Arginine Vasopressin / Q000378:metabolism; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000503:physiopathology*; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects / Q000503:physiopathology*; D010907:Pituitary Hormones / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*
D010907:Pituitary Hormones; D011804:Quinolines; D012702:Serotonin Antagonists; D001127:Arginine Vasopressin; C054363:2-((2-(dimethylamino)ethyl)thio)-3-phenylquinoline; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D013006:Growth Hormone