Hypothesis of Peptic Ulcer: A Modern Classification of a Multifactorial Disease

Caldwell, Stephen H.; McCallum, R. W.

doi:10.1007/978-3-642-75858-4_8

Pharmacology of Peptic Ulcer Disease

1991

DOI: 10.1007/978-3-642-75858-4_8

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Hypothesis of Peptic Ulcer: A Modern Classification of a Multifactorial Disease

Stephen H. Caldwell¹,

R. W. McCallum²

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1998

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Cited by 2 publications

(2 citation statements)

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“…There is little doubt that the etiology of peptic ulcer diseases is complex and multifactorial (Caldwell and McCallum 1991;Vaezi et al 1995). It is extensively accepted, however, that peptic ulcers are caused by an essential imbalance between aggressive factors (acid and pepsin) and defensive mucosal factors (mucus, bicarbonate, and blood flow).…”

mentioning

confidence: 99%

The biochemical and pharmacological properties of a newly synthesized H⁺-K⁺ ATPase inhibitor, 2-dimethylamino-4,5-dihydrothiazolo[4,5:3,4]pyridol-[1,2-a]benzimidazole

Chung¹,

Chang²,

Kyu-Bong³

et al. 1998

Can. J. Physiol. Pharmacol.

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This study was designed to determine the effect of a newly synthesized proton pump inhibitor, 2-dimethylamino-4,5-dihydrothiazolo[4,5:3,4]pyridol[1,2-a]be nzimidazole (YJA20379-2), on gastric H(+)-K(+) ATPase activity, acid secretion, and experimental gastroduodenal lesions or ulcers in rats. YJA20379-2 inhibited in a concentration-dependent manner the proton pump (H(+)-K(+) ATPase) activity in isolated hog gastric mucosal microsomes, therefore, confirming its classification as a proton pump inhibitor. The inhibitory efficacy of YJA20379-2 on the proton pump was about eight times higher than that of omeprazole at pH 7.4. The activity of the inhibited enzyme was not restored by dilution and washout method, so this implied that the inhibition of YJA20379-2 is not reversible. YJA20379-2, given intraduodenally or orally, potently suppressed acid secretion in pylorus-ligated rats, with ED50 values of 3.6 and 7.7 mg.kg(-1), respectively. Pretreatment with YJA20379-2 dose dependently protected the gastric mucosa from damage induced by absolute ethanol, water-immersion stress, indomethacin, and the duodenal mucosa from damage induced by mepirizole in rats, with ED50 values of 11.0, 21.0, 0.5, and 18.7 mg.kg(-1), respectively. Repeated administration of YJA20379-2 also dose dependently accelerated spontaneous healing of acetic acid induced gastric ulcers. These results suggest that YJA20379-2 has potent antisecretory and antiulcer effects, which are exerted by suppression of H(+)-K(+) ATPase activity in gastric parietal cells, such that YJA20379-2 may be useful for the clinical treatment of peptic ulcer diseases.

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mentioning

confidence: 99%

The biochemical and pharmacological properties of a newly synthesized H⁺-K⁺ ATPase inhibitor, 2-dimethylamino-4,5-dihydrothiazolo[4,5:3,4]pyridol-[1,2-a]benzimidazole

Chung¹,

Chang²,

Kyu-Bong³

et al. 1998

Can. J. Physiol. Pharmacol.

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“…The aetiology of peptic ulcer diseases is complex and multifactorial (Caldwell & McCallum 1991;Vaezi et a1 1995). It is widely accepted, however, that peptic ulcers are caused by an imbalance between aggressive factors (acid and pepsin) and defensive mucosal factors (mucus, bicarbonate and blood flow).…”

mentioning

confidence: 99%

Biochemical and Pharmacological Characteristics of 3-Butyryl-8-methoxy-4-[(2-thiophenyl)amino]quinoline, a New Proton-pump Inhibitor, in Rabbit Gastric Microsomes and in Rats

Kim¹,

Chang²,

Chung³

et al. 1998

Journal of Pharmacy and Pharmacology

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We have investigated the properties of the newly synthesized proton-pump inhibitor, 3-butyryl-8-methoxy-4-[(2-thiophenyl)amino]quinoline (YJA20379-6), on gastric mucosal proton-pump (H+/K+-ATPase) activity, gastric acid secretion and gastroduodenal lesions in experimental rats. YJA20379-6 markedly inhibited H+/K+-ATPase activity in rabbit isolated gastric mucosal microsomes, confirming its classification as a proton-pump inhibitor. The inhibitory efficacy of YJA20379-6 on the proton pump was approximately 14-times higher than that of omeprazole at pH 7.4. YJA20379-6 given intraduodenally had a potent inhibitory effect on gastric secretion in pylorus-ligated rats (ED50 22.9 mg kg(-1)) but was less active than omeprazole. Pretreatment of rats with YJA20379-6 dose-dependently protected the gastric mucosa from damage induced by water-immersion stress, indomethacin and absolute ethanol, and the duodenal mucosa from damage induced by mepirizole. Repeated administration of YJA20379-6 also dose-dependently accelerated the spontaneous healing of acetic acid-induced gastric ulcers. These results suggest that YJA20379-6 has potent anti-secretory and anti-ulcer effects which are exerted by suppression of H+/K+-ATPase activity in gastric parietal cells. YJA20379-6 might be useful for the clinical treatment of peptic ulcer diseases.

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Hypothesis of Peptic Ulcer: A Modern Classification of a Multifactorial Disease

Cited by 2 publications

References 172 publications

The biochemical and pharmacological properties of a newly synthesized H⁺-K⁺ ATPase inhibitor, 2-dimethylamino-4,5-dihydrothiazolo[4,5:3,4]pyridol-[1,2-a]benzimidazole

The biochemical and pharmacological properties of a newly synthesized H⁺-K⁺ ATPase inhibitor, 2-dimethylamino-4,5-dihydrothiazolo[4,5:3,4]pyridol-[1,2-a]benzimidazole

Biochemical and Pharmacological Characteristics of 3-Butyryl-8-methoxy-4-[(2-thiophenyl)amino]quinoline, a New Proton-pump Inhibitor, in Rabbit Gastric Microsomes and in Rats

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Hypothesis of Peptic Ulcer: A Modern Classification of a Multifactorial Disease

Cited by 2 publications

References 172 publications

The biochemical and pharmacological properties of a newly synthesized H+-K+ ATPase inhibitor, 2-dimethylamino-4,5-dihydrothiazolo[4,5:3,4]pyridol-[1,2-a]benzimidazole

The biochemical and pharmacological properties of a newly synthesized H+-K+ ATPase inhibitor, 2-dimethylamino-4,5-dihydrothiazolo[4,5:3,4]pyridol-[1,2-a]benzimidazole

Biochemical and Pharmacological Characteristics of 3-Butyryl-8-methoxy-4-[(2-thiophenyl)amino]quinoline, a New Proton-pump Inhibitor, in Rabbit Gastric Microsomes and in Rats

Contact Info

Product

Resources

About

The biochemical and pharmacological properties of a newly synthesized H⁺-K⁺ ATPase inhibitor, 2-dimethylamino-4,5-dihydrothiazolo[4,5:3,4]pyridol-[1,2-a]benzimidazole

The biochemical and pharmacological properties of a newly synthesized H⁺-K⁺ ATPase inhibitor, 2-dimethylamino-4,5-dihydrothiazolo[4,5:3,4]pyridol-[1,2-a]benzimidazole