| Abstract | The synthetic prostanoid Ro 22-6923 was studied for its ability to inhibit gastric secretion and to protect the gastric mucosa against the injurious effects of stress, indomethacin and ethanol. Ro 22-6923 inhibited basal acid secretion when administered intragastrically or intraduodenally to animals with a gastric fistula. The pH of the gastric juice promptly increased and remained above 5 for 3 h after an intragastric dose of 10 micrograms/kg and the pH remained above 4 for more than 3 h after this dose given intraduodenally. The increase in pH was associated with reduction of acid concentration and H+ output. Ro 22-6923 inhibited histamine-stimulated gastric secretion in a perfused stomach preparation with an ED50 of 15 micrograms/kg compared to values of 43, 126 and 289 micrograms/kg for prostaglandin (PG)E2, ranitidine and cimetidine, respectively. The synthetic prostanoid protected the gastric mucosa from the injurious effects of stress (oral ED50 values of 0.2 and greater than 1.0 mg/kg for Ro 22-6923 and PGE2, respectively) and indomethacin (oral ED50 0.07 and 0.06 mg/kg for Ro 22-6923 and PGE2, respectively). Cimetidine and ranitidine, at high doses, were effective against the mucosal damage produced by stress (ED50 values greater than 100 mg/kg) and indomethacin (ED50 values greater than 10 mg/kg). Ro 22-6923, but not PGE2 or 16, 16-dimethyl PGE2, inhibited dibutyryl cyclic AMP-induced [14C]aminopyrine accumulation by isolated parietal cells, indicating that the prostanoid has a direct inhibitory effect on H+ secretion. The results on the antisecretory and cytoprotective properties of Ro 22-6923 suggest this drug could be potentially useful in the pharmacotherapy of peptic ulcer disease. |
| Authors | T S Gaginella, R K Müller, C G Witt, P Rosen, G W Holland, H Gallo-Torres, A C Sullivan |
| Journal | The Journal of pharmacology and experimental therapeutics
(J Pharmacol Exp Ther)
Vol. 232
Issue 1
Pg. 202-7
(Jan 1985)
ISSN: 0022-3565 UNITED STATES |
| PMID | 2578188
(Publication Type: Journal Article)
|
| Chemical References |
- Prostaglandins E
- Prostaglandins E, Synthetic
- Bucladesine
- Dinoprostone
- Indomethacin
- Aminopyrine
- Ro 22-6923
|
| Topics |
- Aminopyrine
(metabolism)
- Animals
- Bucladesine
(pharmacology)
- Dinoprostone
- Dose-Response Relationship, Drug
- Female
- Gastric Acid
(secretion)
- Gastric Fistula
(drug therapy)
- Gastric Mucosa
(drug effects)
- Histamine Release
- Hydrogen-Ion Concentration
- Indomethacin
(pharmacology)
- Parietal Cells, Gastric
(metabolism)
- Prostaglandins E
(pharmacology)
- Prostaglandins E, Synthetic
(pharmacology)
- Rats
- Time Factors
|
