CNS Drugs

, Volume 5, Issue 4, pp 293–310 | Cite as

Therapeutic Potential of Endothelin Receptor Antagonists in Cerebrovascular Disease

  • Toshal R. Patel
Pharmacology and Phatophysiology



The actions of the endothelins (endothelin-I. endothelin-2 and endothelin-3) are mediated via endothelin-A (EA) and endothelin-B (ETB) receptors. the former generally mediating vasoconstriction and the latter vasodilation.

Peptide antagonists selective for either receptor sUbtype [e.g. BQ 123 (ETA) and BQ 788 (ETB)] and combined ETA/ETB receptor antagonists (e.g. PD 145065 and TAK 044) have been developed. More recently. small molecule non-peptide antagonists have also been synthesised. ETA receptor-selective agents include PD 155080 and BMS 182874. while Ro 46-2005 and bosentan are combined ETA/ETB receptor antagonists.

The role of the endothelin family of vasoconstrictor peptides in the pathophysiology of cerebrovascular disease has been speculated upon. Increases in plasma and CSF levels of endothelin-I in delayed vasospasm following subarachnoid haemorrhage and acute ischaemic stroke have implicated the endothelins in these cerebrovascular diseases. The development of non-peptide endothelin receptor antagonists has facilitated investigations into the role of the endothelins in cerebrovascular disease.

The endothelin receptor antagonists have been demonstrated to attenuate cerebral vasospasm following experimental subarachnoid haemorrhage in a variety of species. Additionally, the endothelin receptor antagonists ameliorate neuronal damage following eXIkrimental focal and global cerebral ischaemia. These actions have highlighted the therapeutic potential of endothelin receptor antagonists in cerebrovascular disease.


Bosentan Focal Cerebral Ischaemia Cerebral Vasospasm Cereb Blood Flow Global Cerebral Ischaemia 
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Copyright information

© Adis International Limited 1996

Authors and Affiliations

  • Toshal R. Patel
    • 1
  1. 1.Wellcome Surgical Institute and Hugh Fraser Neuroscience LaboratoriesUniversity of GlasgowGlasgowScotland

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