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CP-66,948: An antisecretory histamine H2-receptor antagonist with mucosal protective properties

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Abstract

CP-66,948 is a histamine H2-receptor antagonist with gastric antisecretory activity and mucosal protective properties. The affinity of CP-66,948 for the guinea pig atria histamine H2-receptor is 15 times greater than that of cimetidine and seven times greater than that of ranitidine.In vivo, the ED50 value for inhibition of gastric acid secretion in pylorusligated rats is 2 mg/kg intraduodenally, and in histamine or pentagastrin-stimulated Heidenhain pouch dogs the antisecretory ED50 values are 0.3 mg/kgper os and 1.0 mg/kgper os, respectively. CP-66,948 also inhibits ethanol-induced gastric hemorrhagic lesions in rats following either oral or systemic administration (ED50 values of 12 mg/kgper os and 6 mg/kg subcutaneously). In addition, the mucosal protective activity is independent of prostaglandin synthesis. CP-66,948 inhibits gastric acid secretion in man, and its mucosal protective activity may provide additional benefits in peptic ulcer therapy.

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Author notes

  1. James J. Maciejko PhD

    Present address: Center for Cardiovascular Research, Sinai Hospital of Detroit, 48235, Detroit, MI

Authors and Affiliations

  1. Department of Metabolic Diseases and General Pharmacology, Central Research Division, Pfizer Inc., 06340, Groton, CT

    John P. Hakkinen MS, William F. Holt PhD, Carl J. Goddard MS, Peter J. Oates PhD, William R. Murphy PhD, James J. Maciejko PhD &  Lawrence A. Reiter PhD

  2. Department of Medicinal Chemistry, Central Research Division, Pfizer Inc., Eastern Point Road, 06340, Groton, CT

    John P. Hakkinen MS, William F. Holt PhD, Carl J. Goddard MS, Peter J. Oates PhD, William R. Murphy PhD, James J. Maciejko PhD &  Lawrence A. Reiter PhD

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  1. John P. Hakkinen MS
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  2. William F. Holt PhD
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  3. Carl J. Goddard MS
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  4. Peter J. Oates PhD
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  5. William R. Murphy PhD
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  7. Lawrence A. Reiter PhD
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Hakkinen, J.P., Holt, W.F., Goddard, C.J. et al. CP-66,948: An antisecretory histamine H2-receptor antagonist with mucosal protective properties. Digest Dis Sci 36, 1721–1728 (1991). https://doi.org/10.1007/BF01296616

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  • DOI: https://doi.org/10.1007/BF01296616

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