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Synthesis and in vitro Pharmacological Profile of Potent and Selective Peptidic V1a Receptor Agonists.

  • Kazimierz Wisniewski
  • Robert Galyean
  • Hiroe Taki
  • Sudar Alagarsamy
  • Glenn Croston
  • Regent Laporte
  • Claudio D. Schteingart
  • Pierre J-M. Rivière
Part of the Advances in Experimental Medicine and Biology book series (volume 611)

Introduction

The neurohypophyseal hormone, 8-arginine-vasopressin (AVP, 1), produces arterial vasoconstriction by activation of the V1a vasopressin receptor (V1aR) located in vascular smooth muscle. This vasopressor effect can be used to treat vasodilatory hypotension in critical care and other conditions [1]. AVP is the endogenous ligand for the V1aR and the two additional vasopressin receptors (V1bR and V2R), and also binds to the oxytocin receptor (OTR). When used as a vasopressor, the lack of selectivity of AVP could possibly generate unwanted side effects such as V2 receptor mediated antidiuresis and release of coagulation factors. In order to find new, more V1a selective agonists, analogs of 1 of the general structure [X2,Ile3,Y4,Z8]VP have been designed, synthesized and tested in vitro.

Results and Discussion

Enhanced selectivity towards V1aR in a rat in vivo model for [Phe 2,Ile 3,Orn 8]VP, 2, was first reported by Huguenin [ 2]. The peptide was tested in our in vitroRGA assays...

Keywords

Vasopressin Receptor Peptide Assembly Diamino Acid Primary Amide Heteroaromatic Ring 
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.

Notes

Acknowledgments

he authors wish to thank Marlene Brown and Monica Wolfe for their excellent technical assistance.

References

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    Landry, D. W., Levin, H. R., Gallant, E. M., Ashton, R. C. Jr., Seo, S., D'Alessandro, D., Oz, M. C. and Oliver, J. A., Circulation, 95, 1122–1125 (1997).Google Scholar
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    Huguenin, R. L., Helv. Chim. Acta, 47, 1934–1941 (1964).CrossRefGoogle Scholar
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    Andres, M., Trueba, M. and Guillon, G., Br. J. Pharm. 135, 1828–1836 (2002).CrossRefGoogle Scholar
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    Fukuyama, T., Jow, C.-K. and Cheung, M., Tetrahedron Lett. 36, 6373–6374 (1995).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Kazimierz Wisniewski
    • 1
  • Robert Galyean
    • 1
  • Hiroe Taki
    • 1
  • Sudar Alagarsamy
    • 1
  • Glenn Croston
    • 1
  • Regent Laporte
    • 1
  • Claudio D. Schteingart
    • 1
  • Pierre J-M. Rivière
    • 1
  1. 1.General Atomics CourtFerring Research Institute Inc.San DiegoUSA

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