HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Differences between peptide and nonpeptide B(2) bradykinin receptor antagonists in blocking bronchoconstriction and hypotension induced by bradykinin in anesthetized Guinea pigs.

Abstract
We have compared the in vivo activity of the bradykinin B(2) receptor peptide antagonists MEN 11270 and Icatibant versus the nonpeptide antagonist FR 173657, after intravenous (i.v.) and intratracheal (i.t.) administration, on the bradykinin (BK)-induced bronchoconstriction and hypotension in anesthetized guinea pigs. We have also assessed the affinity of these antagonists for B(2) receptors in guinea pig lung membranes by radioligand binding and the metabolic stability of peptide antagonists in guinea pig plasma and tissue homogenates. The i.v. administration of MEN 11270, Icatibant, or FR 173657 induced a dose-dependent (10-100 nmol/kg) inhibition of both hypotension and bronchoconstriction induced by bradykinin (10 nmol/kg i.v.). The inhibitory effect of MEN 11270 and Icatibant was comparable both in terms of potency and time course, whereas FR 173657 was less potent and shorter acting. After i.t. administration MEN 11270 and Icatibant (10-100 nmol/kg) dose dependently inhibited both bronchoconstriction and hypotension, whereas FR 173657 (10-100 nmol/kg) reduced bronchoconstriction without affecting hypotension. The antibronchoconstrictor effect of MEN 11270 was more prolonged than that of Icatibant and FR 173657, whereas no differences were found between the peptide antagonists in inhibiting hypotension. These findings indicated that, in vivo, the peptide antagonists are more potent and longer lasting than FR 173657 acting on bradykinin B(2) receptors in guinea pig airways and in the vascular system. The greater efficacy of the antagonists in blocking airway compared with vascular B(2) receptors after topical administration suggests that they can block airway B(2) receptors with little systemic effects.
AuthorsM Tramontana, A Lecci, S Meini, X Montserrat, J Pascual, S Giuliani, L Quartara, C A Maggi
JournalThe Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 296 Issue 3 Pg. 1051-7 (Mar 2001) ISSN: 0022-3565 [Print] United States
PMID11181940 (Publication Type: Journal Article)
Chemical References
  • Anti-Inflammatory Agents, Non-Steroidal
  • Bradykinin Receptor Antagonists
  • FR 173657
  • MEN 11270
  • Oligopeptides
  • Peptides, Cyclic
  • Quinolines
  • Receptor, Bradykinin B2
  • Tritium
  • icatibant
  • Bradykinin
Topics
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal (pharmacology, therapeutic use)
  • Blood Pressure (drug effects)
  • Bradykinin (analogs & derivatives, metabolism, pharmacology, therapeutic use)
  • Bradykinin Receptor Antagonists
  • Bronchoconstriction (drug effects)
  • Cell Membrane (metabolism)
  • Disease Models, Animal
  • Drug Interactions
  • Drug Stability
  • Guinea Pigs
  • Hypotension (chemically induced, prevention & control)
  • Infusions, Intravenous
  • Lung (cytology)
  • Male
  • Oligopeptides (metabolism, pharmacology, therapeutic use)
  • Peptides, Cyclic (metabolism, pharmacology, therapeutic use)
  • Quinolines (metabolism, pharmacology, therapeutic use)
  • Receptor, Bradykinin B2
  • Tritium

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: