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, Volume 38, Issue 1–2, pp 158–164 | Cite as

Pharmacological profile of new thioperamide derivatives at histamine peripheral H1-, H2-, H3-receptors in guinea-pig

  • E. Barocelli
  • V. Ballabeni
  • A. Caretta
  • F. Bordi
  • C. Silva
  • G. Morini
  • M. Impicciatore
Allergy and Histamine

Abstract

The recent availability of potent and selective ligands, namely R-(α)-methylhistamine and thioperamide, led to conclusive progresses as regards histamine H3-receptor knowledge. The aim of this work is to investigate byin vitro tests the pharmacological properties of new amino and methyl derivatives of the H3-antagonist thioperamide. Such original compounds, developed by the modulation of the thioperamide imidazolyl moiety, were assayed at guinea-pig ileal contractile H1-, atrial chronotropic H2- and enteric neuronal H3-receptors.

None of the drugs exhibited interaction with H1 or H2 sites. On electrically stimulated ileum, two of the thioperamide methyl derivatives competitively antagonized the inhibitory effect of the H3-agonist R-(α)-methylhistamine. On the basis of the Schild analysis, the more active isomer (compound IV) displayed an affinity at H3-receptors only five times lower than thioperamide. These results could contribute to elucidate further the structural features required to develop potent and selective H3-antagonists. On the other hand, to prove the hypothesized apparent heterogeneity between peripheral and central H3-sites, as emerged by pharmacological and binding studies, autoradiographic investigations are in progress.

Keywords

Methyl Structural Feature Histamine Ileal Pharmacological Property 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Birkhäuser Verlag 1993

Authors and Affiliations

  • E. Barocelli
    • 1
  • V. Ballabeni
    • 1
  • A. Caretta
    • 1
  • F. Bordi
    • 2
  • C. Silva
    • 2
  • G. Morini
    • 3
  • M. Impicciatore
    • 1
  1. 1.Institute of Pharmacology and Pharmacognosy, Department of PharmacyUniversity of ParmaParmaItaly
  2. 2.Institute of Pharmaceutical Chemistry, Department of PharmacyUniversity of ParmaParmaItaly
  3. 3.Institute of Pharmaceutical Technology, Department of PharmacyUniversity of ParmaParmaItaly

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