TY - JOUR
T1 - Acotiamide hydrochloride (Z-338), a novel prokinetic agent, restores delayed gastric emptying and feeding inhibition induced by restraint stress in rats
AU - Seto, K.
AU - Sasaki, T.
AU - Katsunuma, K.
AU - Kobayashi, N.
AU - Tanaka, K.
AU - Tack, J.
PY - 2008/9
Y1 - 2008/9
N2 - Acotiamide hydrochloride (Z-338) is a member of new class prokinetic agents currently being developed for the treatment of functional dyspepsia (FD). DNA microarray analysis showed that acotiamide altered the expressions of stress-related genes such as γ-aminobutyric acid (GABA) receptors, GABA transporters and neuromedin U (NmU) in the medulla oblongata or hypothalamus after administration of acotiamide. Therefore, effects of acotiamide on stress-related symptoms, delayed gastric emptying and feeding inhibition, in rats were examined. Acotiamide significantly improved both delayed gastric emptying and feeding inhibition in restraint stress-induced model, but did not affect both basal gastric emptying and feeding in intact rats, indicating that acotiamide exerted effects only on gastric emptying and feeding impaired by the stress. On the other hand, mosapride showed significant acceleration of gastric emptying in intact and restraint stress-induced model, and itopride showed no effect on restraint stress-induced delayed gastric emptying. In addition, gene expression of NmU increased by restraint stress was suppressed by administration of acotiamide, while acotiamide had no effect on delayed gastric emptying induced by an intracerebroventricular administration of NmU, suggesting that the suppressive effect of acotiamide on gene expression of NmU might be important to restore delayed gastric emptying or feeding inhibition induced by restraint stress. These findings suggest that acotiamide might play an important role in regulation of stress response. As stress is considered to be a major contributing factor in the development of FD, the observed effects may be relevant for symptom improvement in FD.
AB - Acotiamide hydrochloride (Z-338) is a member of new class prokinetic agents currently being developed for the treatment of functional dyspepsia (FD). DNA microarray analysis showed that acotiamide altered the expressions of stress-related genes such as γ-aminobutyric acid (GABA) receptors, GABA transporters and neuromedin U (NmU) in the medulla oblongata or hypothalamus after administration of acotiamide. Therefore, effects of acotiamide on stress-related symptoms, delayed gastric emptying and feeding inhibition, in rats were examined. Acotiamide significantly improved both delayed gastric emptying and feeding inhibition in restraint stress-induced model, but did not affect both basal gastric emptying and feeding in intact rats, indicating that acotiamide exerted effects only on gastric emptying and feeding impaired by the stress. On the other hand, mosapride showed significant acceleration of gastric emptying in intact and restraint stress-induced model, and itopride showed no effect on restraint stress-induced delayed gastric emptying. In addition, gene expression of NmU increased by restraint stress was suppressed by administration of acotiamide, while acotiamide had no effect on delayed gastric emptying induced by an intracerebroventricular administration of NmU, suggesting that the suppressive effect of acotiamide on gene expression of NmU might be important to restore delayed gastric emptying or feeding inhibition induced by restraint stress. These findings suggest that acotiamide might play an important role in regulation of stress response. As stress is considered to be a major contributing factor in the development of FD, the observed effects may be relevant for symptom improvement in FD.
KW - Acotiamide
KW - Feeding inhibition
KW - Functional dyspepsia
KW - Gastric emptying
KW - Prokinetic agent
KW - Stress
UR - http://www.scopus.com/inward/record.url?scp=49749087225&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=49749087225&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2982.2008.01135.x
DO - 10.1111/j.1365-2982.2008.01135.x
M3 - Article
C2 - 18482254
AN - SCOPUS:49749087225
SN - 1350-1925
VL - 20
SP - 1051
EP - 1059
JO - Neurogastroenterology and Motility
JF - Neurogastroenterology and Motility
IS - 9
ER -