BIBP 3226, the first selective neuropeptide Y1 receptor antagonist: A review of its pharmacological properties

BIBP 3226, the first selective neuropeptide Y1 receptor antagonist: A review of its... Based on the assumption that the pharmacophoric groups interacting with the Y1 receptor are located in the C-terminal part of neuropeptide Y, low molecular weight compounds with high affinity and selectivity for the Y1 receptor were designed and synthesized. The prototype BIBP 3226 possesses affinity for the Y1 receptor in the nanomolar range. In addition, this compound is selective displaying rather low affinity for Y2, Y3, Y4 and a set of 60 other receptors. Both biochemical and pharmacological studies showed that BIBP 3226 behaves as a competitive antagonist. Using BIBP 3226 it was possible to investigate the role of NPY and/or Y1 receptors in blood pressure regulation. The interesting observation was that antagonism to Y1 receptors had no major influence on the basal blood pressure but attenuated stress induced hypertension. This strongly supports the hypothesis that NPY is mainly released during stress involving intense sympathetic nervous system activation. Moreover, BIBP 3226 can be used to characterize NPY receptor subtypes. For instance, we were able to show that presynaptic NPY receptors mediating catecholamine release do not solely belong to the Y2 subtype, but that presynaptic Y1 receptors also exist. In conclusion, BIBP 3226 has been shown to be an important tool for the elucidation of the physiological role of Y1 receptors in the cardiovascular system. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Regulatory Peptides Elsevier

BIBP 3226, the first selective neuropeptide Y1 receptor antagonist: A review of its pharmacological properties

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Publisher
Elsevier
Copyright
Copyright © 1996 Elsevier Ltd
ISSN
0167-0115
eISSN
1873-1686
DOI
10.1016/0167-0115(96)00074-2
Publisher site
See Article on Publisher Site

Abstract

Based on the assumption that the pharmacophoric groups interacting with the Y1 receptor are located in the C-terminal part of neuropeptide Y, low molecular weight compounds with high affinity and selectivity for the Y1 receptor were designed and synthesized. The prototype BIBP 3226 possesses affinity for the Y1 receptor in the nanomolar range. In addition, this compound is selective displaying rather low affinity for Y2, Y3, Y4 and a set of 60 other receptors. Both biochemical and pharmacological studies showed that BIBP 3226 behaves as a competitive antagonist. Using BIBP 3226 it was possible to investigate the role of NPY and/or Y1 receptors in blood pressure regulation. The interesting observation was that antagonism to Y1 receptors had no major influence on the basal blood pressure but attenuated stress induced hypertension. This strongly supports the hypothesis that NPY is mainly released during stress involving intense sympathetic nervous system activation. Moreover, BIBP 3226 can be used to characterize NPY receptor subtypes. For instance, we were able to show that presynaptic NPY receptors mediating catecholamine release do not solely belong to the Y2 subtype, but that presynaptic Y1 receptors also exist. In conclusion, BIBP 3226 has been shown to be an important tool for the elucidation of the physiological role of Y1 receptors in the cardiovascular system.

Journal

Regulatory PeptidesElsevier

Published: Aug 27, 1996

References

  • Neuropeptide Y and energy balance: one way ahead for the treatment of obesity?
    Dryden, S.; Frankish, H.; Qiong, Wang; Williams, G.
  • Effect of neuropeptide Y on cardiac output, its distribution, regional blood flow and organ resistances in the pithed rat
    Maclean, M.R.; Hiley, C.R.
  • Neuropeptide Y potentiates the effects of various vasoconstrictor agents on rabbit blood vessels
    Edvinsson, L.; Emson, P.; Häkanson, R.; Wahlestedt, C.
  • Characterization of vascular receptors for neuropeptide Y
    Grundemar, L.; Mörner, S.E.J.M.; Högestätt, E.D.; Wahlestedt, C.; Häkanson, R.
  • Stress induced mesenteric vasoconstriction in rats is mediated by neuropeptide Y Y1 receptors
    Zukowska-Grojec, Z.; Dayao, E.; Karwatowska-Prokopczuk, E.; Hauser, G.J.; Doods, H.N.

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