The gastric antisecretory activity of a phenothiazine molecule, LM 24056.
The effect on the gastric secretion of the phenothiazine molecule N,N-dimethyl-10-(3-quinuclidinyl)-2-phenothiazine sulfonamide (LM24056) was studied in dogs equipped with gastric fistula and denervated pouch. The gastric stimulation was obtained either by exogenous stimulants (gastrin, gastrin + bethanechol, histamine) or by endogenous ones released by feeding gastrin; LM 24056 was infused i.v. 1. I.v. administration of 1.25 to 5 mg . kg-1 . h-1 of LM 24056 had a nearly complete inhibitory action on gastric juice secretion (acid and pepsin), on gastrin- and gastrin + bethanechol-stimulated secretion. The LM, 24056 concentration which produced 50% inhibition (IC50%) of acid and pepsin secretion was about 1.25 mg . kg-1 . h-1. 2. LM 24056 appeared to be unable to reduce the histamine-stimulated secretion. 3. I.v. administration of 1 to 30 mg . h-1 of LM 24056 reduced or abolished both gastric acid secretion and gastrin release. The IC50 was 5 mg . h-1 (or about 0.5 mg . kg-1 . h-1) for both responses. The possible mechanism of action of LM 24056 is discussed in comparison with those of H2-receptor antagonists, of atropine and of pirenzepine, respectively.
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001626:Bethanechol Compounds / Q000494:pharmacology; D004285:Dogs; D005502:Food; D005744:Gastric Acid / Q000378:metabolism; D005750:Gastric Juice / Q000378:metabolism*; D005755:Gastrins / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D010434:Pepsin A / Q000378:metabolism; D010640:Phenothiazines / Q000494:pharmacology*
D000897:Anti-Ulcer Agents; D001626:Bethanechol Compounds; D005755:Gastrins; D010640:Phenothiazines; C028720:LM 24056; D006632:Histamine; D010434:Pepsin A