Bradykinin Receptor Antagonists Containing N-Substituted Amino Acids:  In Vitro and in Vivo B2 and B1 Receptor Antagonist Activity

Author:

Goodfellow Val S.1,Marathe Manoj V.1,Kuhlman Karen G.1,Fitzpatrick Timothy D.1,Cuadrado David1,Hanson Wendy1,Zuzack John S.1,Ross Sherman E.1,Wieczorek Maciej1,Burkard Michael1,Whalley Eric T.1

Affiliation:

1. Departments of New Leads Discovery, Biochemistry, and Pharmacology, Cortech Inc., 6850 North Broadway, Denver, Colorado 80221

Publisher

American Chemical Society (ACS)

Subject

Drug Discovery,Molecular Medicine

Reference48 articles.

1. Abbreviations of nonstandard amino acids or mimetics:  Cpg = cyclopentylglycine, δ-Gpa = 5-guanidinopentanoic acid, Igl = 2- indanylglycine, NBng =N-benzylglycine, NChg =N-cyclohexylglycine, NCpg =N-cyclopentylglycine, NMchN-(methylcyclohexyl)glycine, NPeg =N-phenethylglycine, NPhg =N-phenylglycine. Abbreviations for standard bradykinin antagonists:  NPC-567= [d-Arg0,Hyp3,d-Phe7]-bradykinin, NPC17761 = [d-Arg0,Hyp3,d-(4S)-(thiophenyl)-Pro7,Oic8]-bradykinin, NPC17731 = [d-Arg0,Hyp3,d-(4S)-(oxypropyl)-Pro7,Oic8]-bradykinin, HOE-140 = [d-Arg0,Hyp3,Thi5,d-Tic7,Oic8]-bradykinin. CP-0127 is the bis(succinimidohexane) cross-linked homodimer formed from [d-Arg0,Hyp3,Cys6,d-Phe7,Leu8]-bradykinin.

2. Effect of bradykinin antagonists on bradykinin-induced plasma extravasation, venoconstriction, prostaglandin E2 release, nociceptor stimulation and contraction of the iris sphincter muscle in the rabbit

3. Characterization of the arachidonic acid metabolites mediating bradykinin and noradrenaline hyperalgesia

4. Bradykinin as a pain mediator: receptors are localized to sensory neurons, and antagonists have analgesic actions.

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