The inhibitory effect on gastric secretion of a
phenothiazine molecule, N,N-dimethyl-10-(3-quinuclidinyl)-2-phenothiazine
sulfonamide (
LM 24056), was studied in dogs equipped with
gastric fistula (GF) and Heidenhain denervated pouch (HP).
LM 24056 was infused intravenously before exogenous stimulations started: the gastric stimulation ws obtained either by
gastrin, by combination of
gastrin +
bethanechol (subthreshold dose) or by
histamine. 1. On
gastrin-stimulated secretion, preliminary infusion of
LM 24056 results in a weak and non-significant reduction on GF
acid secretion, while on HP, the inhibition is significant with 1 and 2 micrograms x kg-1 x h-1 of
gastrin. The
LM 24056 concentrations which produced 50% inhibition (IC50) of
acid secretion is close to 0.5 mg x min-1. 2.
LM 24056 exerts a strong inhibitory effect on combination
gastrin +
bethanechol-stimulated
acid and
pepsin secretions on GH and HP. IC50 is close to 0.25 mg x min-1. 3.
LM 24056 is able to delay the
histamine-stimulated
acid secretion. There are some differences in the gastric inhibitory effects in relation to the moment of
LM 24056 administration regarding exogenous stimulant:
LM 24056 seems to be able to compete
gastrin and to delay the normal
histamine stimulation. The most important inhibitory effect is exerted on combination
gastrin +
bethanechol.
LM 24056 could act as an antigastrinic substance.