A double-blind placebo-controlled study of buspirone-stimulated prolactin release in non-ulcer dyspepsia--are central serotoninergic responses enhanced?
BACKGROUND
Dyspepsia is a common symptom for which an organic cause is found in only 40% of patients. When no cause is apparent and the dyspepsia is considered to be idiopathic, a diagnosis of non-ulcer dyspepsia is made. The pathophysiology of non-ulcer dyspepsia is poorly understood and numerous theories have been put forward, including a theory of enhanced central serotoninergic receptor sensitivity.


OBJECTIVE
To determine the sensitivity of serotonin receptors in non-ulcer dyspepsia.


METHODS
Using a randomized, double-blind, placebo-controlled design, we compared buspirone (a serotonin type 1a partial agonist)-stimulated prolactin release in 50 patients and 59 healthy comparison subjects. Buspirone, 30 mg, or matching placebo was administered on two separate occasions and prolactin release over 180 min was monitored. Patients and healthy subjects received both treatments in random order, 1 week apart.


RESULTS
Overall, patients with non-ulcer dyspepsia had greater prolactin release in response to the buspirone challenge than the healthy comparison subjects, with differences most significant at 90 min following the challenge. Enhancement occurred in patients both with and without Helicobacter pylori infection. Female subjects, both patients and healthy volunteers, showed a greater response to buspirone than male subjects, and the augmentation of response observed in male and female patients was greater in females.


CONCLUSIONS
Patients with non-ulcer dyspepsia have enhanced central serotoninergic responses and such responses are independent of H. pylori infection. Blockade of such receptors might be an appropriate therapeutic strategy.
Dinan
T G
TG
Department of Pharmacology and Therapeutics, The Cork Clinic, University College Cork, Western Road, Cork, Ireland. tdinan@indigo.ie
Mahmud
N
N
Rathore
O
O
Thakore
J
J
Scott
L V
LV
Carr
E
E
Naesdal
J
J
O'Morain
C A
CA
Keeling
P W
PW
D000328:Adult; D002065:Buspirone / Q000494:pharmacology*; D004311:Double-Blind Method; D004415:Dyspepsia / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000382:microbiology; D005260:Female; D016481:Helicobacter Infections / Q000150:complications / Q000453:epidemiology; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D011388:Prolactin / Q000097:blood*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D011388:Prolactin; D002065:Buspirone