In:
Annals of the New York Academy of Sciences, Wiley, Vol. 1009, No. 1 ( 2003-12), p. 228-233
Abstract:
A bstract : Clonidine‐like drugs (hybrid drugs) reduce blood pressure by acting centrally at both a 2 ‐adrenergic receptors (a 2 AR) and I 1 receptors (I 1 R). Some attempts at cloning I 1 R have failed, probably because of the lack of selectivity of the ligands. Recently, compounds acting exclusively at I 1 R were synthesized: LNP 911, LNP509, and S23515. For example, LNP911 has a K d value of 1.7 nmol/L at I 1 R. LNP509 and S23515 reduce blood pressure when injected centrally in anesthetized animals, whereas S23757 behaves as an antagonist of hypotensive imidazolines. LNP509 reduces blood pressure even in genetically engineered mice lacking functional a 2 AR. An exclusive action at central I 1 R is therefore sufficient to modify blood pressure. With the help of drugs selective for I 1 R and a‐methylnoradrenaline, selective for a 2 AR, we showed that imidazoline and a 2 ‐adrenergic mechanisms interact synergistically in controlling the blood pressure. Such a synergism may explain the very powerful hypotensive effects of hybrid drugs. The new ligands selective for I 1 R will be very helpful to investigate the molecular features and the signaling system of I 1 R.
Type of Medium:
Online Resource
ISSN:
0077-8923
,
1749-6632
DOI:
10.1196/annals.1304.028
Language:
English
Publisher:
Wiley
Publication Date:
2003
detail.hit.zdb_id:
2834079-6
detail.hit.zdb_id:
211003-9
detail.hit.zdb_id:
2071584-5
SSG:
11
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