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Inhibitors of histidine decarboxylase decrease basal gastric acid secretion in the rat.

V S Westerberg¹, J D Geiger

¹Department of Pharmacology and Therapeutics, University of Manitoba, Faculty of Medicine, Winnipeg.

Pharmacology, Biochemistry, and Behavior

|November 1, 1987

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Two histidine decarboxylase inhibitors, (s)-alpha-fluoromethylhistidine (FMHd) and (s)-alpha-fluoromethylhistamine (FMHm), were tested for their effects on gastric acid secretion. Both compounds reduced acid output, with FMHm also increasing intraluminal pH.

Area of Science:

Pharmacology
Gastroenterology

Background:

Histamine plays a key role in regulating gastric acid secretion.
Histidine decarboxylase (HDC) is the enzyme responsible for histamine synthesis.

Purpose of the Study:

To investigate the efficacy of two HDC inhibitors, (s)-alpha-fluoromethylhistidine (FMHd) and (s)-alpha-fluoromethylhistamine (FMHm), in inhibiting basal gastric acid secretion.
To assess the impact of these inhibitors on gastric secretion volume and intraluminal pH.

Main Methods:

Administration of varying doses of FMHd and FMHm to subjects.
Measurement of basal gastric acid secretion, total secretion volume, and intraluminal pH.
Evaluation of the effect of compounds on stress-induced gastric ulcers.

Main Results:

Related Experiment Videos

FMHd at 50 and 100 mg/kg significantly decreased basal gastric acid secretion and total secretion volume, without altering intraluminal pH.
FMHm demonstrated a reduction in gastric acid secretion, an increase in intraluminal pH, and a moderate decrease in total secretion volume.
Neither FMHd nor FMHm affected the severity of gastric ulcers induced by cold restraint stress.

Conclusions:

Both FMHd and FMHm show potential as inhibitors of gastric acid secretion.
FMHm may offer additional benefits by increasing intraluminal pH, potentially contributing to acid control.
Further research is warranted to explore the therapeutic applications of these histidine decarboxylase inhibitors in managing acid-related gastrointestinal disorders.