Respective contributions of alpha-adrenergic and non-adrenergic mechanisms in the hypotensive effect of imidazoline-like drugs

Br J Pharmacol. 2001 May;133(2):261-6. doi: 10.1038/sj.bjp.0704080.


The hypotensive effect of imidazoline-like drugs, such as clonidine, was first attributed to the exclusive stimulation of central alpha2-adrenoceptors (alpha2ARs). However, a body of evidence suggests that non-adrenergic mechanisms may also account for this hypotension. This work aims (i) to check whether imidazoline-like drugs with no alpha2-adrenergic agonist activity may alter blood pressure (BP) and (ii) to seek a possible interaction between such a drug and an alpha2ARs agonist alpha-methylnoradrenaline (alpha-MNA). We selected S23515 and S23757, two imidazoline-like drugs with negligible affinities and activities at alpha2ARs but with high affinities for non-adrenergic imidazoline binding sites (IBS). S23515 decreased BP dose-dependently (-27+/-5% maximal effect) when administered intracisternally (i.c.) to anaesthetized rabbits. The hypotension induced by S23515 (100 microg kg(-1) i.c.) was prevented by S23757 (1 mg kg(-1) i.c.) and efaroxan (10 microg kg(-1) i.c.), while these compounds, devoid of haemodynamic action by themselves, did not alter the hypotensive effect of alpha-MNA (3 and 30 microg kg(-1) i.c.). Moreover, the alpha2ARs antagonist rauwolscine (3 microg kg(-1) i.c.) did not prevent the effect of S23515. Finally, whilst 3 microg kg(-1) of S23515 or 0.5 microg kg(-1) of alpha-MNA had weak hypotensive effects, the sequential i.c. administration of these two drugs induced a marked hypotension (-23+/-2%). These results indicate that an imidazoline-like drug with no alpha2-adrenergic properties lowers BP and interacts synergistically with an alpha(ARs agonist.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / pharmacology*
  • Blood Pressure / drug effects*
  • Cattle
  • Cisterna Magna
  • Cyclic AMP / metabolism
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • HT29 Cells
  • Hemodynamics / drug effects
  • Humans
  • Imidazoles / administration & dosage
  • Imidazoles / pharmacology*
  • In Vitro Techniques
  • Injections
  • Male
  • Oxazoles / pharmacology*
  • Rabbits
  • Radioligand Assay
  • Receptors, Adrenergic, alpha / drug effects*


  • 2-(2-fluoro-5-methylphenyl)-4,5-dihydro-1H-imidazole
  • 5-(2-bnromophenoxy)methyl-2-amino-4,5-dihydro-1,3-oxazole
  • Antihypertensive Agents
  • Imidazoles
  • Oxazoles
  • Receptors, Adrenergic, alpha
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Cyclic AMP