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N-Methyldimaprit (SK&F92054). A chemical control for the histamine H2-receptor agonist dimaprit

Agents and Actions volume 19, pages 18–25 (1986)Cite this article

Abstract

Dimaprit analogues having alkyl substituents on the isothiourea group have no detectable H2-agonist activity on the guinea-pig atrium. N-Methyldimaprit [S-[3-(N,N-dimethylamino)propyl]-N′-methylisothiourea] (SK&F92054) is identified as a compound which may serve as a suitable chemical control when studying the actions of dimaprit at putative H2-histamine receptors. Concentrations of N-methyl-dimaprit (up to 3×10−3 M) had no agonist activityin vitro on the guinea-pig atrium (<0.005% of the activity of histamine), rat uterus (up to 2×10−3M) or as a stimulant of guinea-pig ventricular adenylate cyclase (up to 10−3 M). N-Methyldimaprit at 10−3 M also did not significantly stimulate acid secretion in the rat isolated stomach preparation; it was a very weak stimulant of gastric acid secretion (<0.2% of the activity of histamine)in vivo in the lumen-perfused stomach of the anaesthetised rat but exhibited marked tachyphylaxis on repeated administration. N-Methyldimaprit, has two basic centres, macroscopic pKa values 8.31 and 9.58 at 40°C.

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Affiliations

  1. Smith Kline and French Research Limited, The Frythe, Welwyn, Hertfordshire, England, U.K.

    R. C. Blakemore, C. R. Ganellin, B. K. Leigh, M. E. Parsons, C. A. Price, I. R. Smith & W. Tertiuk

Authors
  1. R. C. Blakemore
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  2. C. R. Ganellin
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  3. B. K. Leigh
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  4. M. E. Parsons
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  5. C. A. Price
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  6. I. R. Smith
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  7. W. Tertiuk
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Blakemore, R.C., Ganellin, C.R., Leigh, B.K. et al. N-Methyldimaprit (SK&F92054). A chemical control for the histamine H2-receptor agonist dimaprit. Agents and Actions 19, 18–25 (1986). https://doi.org/10.1007/BF01977251

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  • DOI: https://doi.org/10.1007/BF01977251

Keywords

  • Histamine
  • Acid Secretion
  • Gastric Acid Secretion
  • Chemical Control
  • Alkyl Substituent