Related Experiment Videos
[From alpha 2-adrenergic to endazoline receptors]
P Bousquet1, J Feldman, E Tibirica
1Laboratoire de pharmacologie cardio-vasculaire et rénale, CNRS UA 589, faculté de médecine, université Louis-Pasteur, Strasbourg, France.
Archives Des Maladies Du Coeur Et Des Vaisseaux
|December 1, 1989
Summary
Imidazoline receptors in the brainstem mediate the hypotensive effects of clonidine-like drugs, acting on a newly discovered endogenous substance called endazoline.
Area of Science:
- Neuropharmacology
- Cardiovascular Physiology
Background:
- Imidazolines, like clonidine, exert central hypotensive effects.
- Their mechanism involves non-catecholamine binding sites, termed imidazoline receptors.
Purpose of the Study:
- To investigate the specific binding sites and endogenous ligands involved in the central hypotensive action of imidazolines.
- To explore the potential for developing novel antihypertensive agents with reduced side effects.
Main Methods:
- Investigated binding of radiolabeled clonidine in the lateral reticular nucleus (LRN) of the brainstem.
- Tested hypotensive effects of catecholamines and phenylethylamines in the LRN.
- Isolated and characterized an endogenous ligand for imidazoline receptors from brain tissue.
Main Results:
- Noradrenaline and other catecholamines did not exhibit hypotensive effects in the LRN, unlike imidazolines.
- Specific clonidine binding sites, insensitive to noradrenaline, were identified in the LRN.
- An endogenous, non-catecholamine substance (provisionally named endazoline) recognized by these receptors was isolated.
Conclusions:
- Hypotensive effects of imidazoline-like drugs are mediated by specific brainstem receptors binding an endogenous ligand, endazoline.
- Rilmenidine shows higher selectivity for imidazoline sites than clonidine, suggesting potential for novel antihypertensives.
- Further structure-activity relationship studies are needed to develop selective central antihypertensive agents.