Targeting Endothelin in Alzheimer’s Disease: A Promising Therapeutic Approach

Table 1

Various endothelin receptor agonists and antagonists on which preclinical studies are done and that are found to be effective in the prevention of Alzheimer’s disease.

S. no	Drug	Agonist/antagonist	Mechanism of action	Reference
1	Bosentan	Endothelin receptor antagonist	Decrease inflammatory mediators and vascular dysfunction in brain carotid arteries, hence, decrease cerebrospinal blood flow	[48]
2	Tezosentan	ETA/ETB receptor antagonist	Reduce oxidative stress	[13]
3	BQ123	ETA/ETB receptor antagonist	Reduce oxidative stress	[13]
4	BMS 182874	ETA/ETB receptor antagonist	Reduce oxidative stress	[13]
5	IRL-1620 0.6 μg/kg	Endothelin receptor agonist	Decreased oxidative stress, increased VEGF and NGF. Direct stimulation of endothelin receptor B. Antiapoptotic factor is shown against neurotoxicity by inhibiting L-type voltage-sensitive calcium channel (VSCCs)	[51, 103–105]
7	BQ123	ETA/ETB receptor antagonist	Reduce oxidative stress	[13]
8	BMS 182874	ETA/ETB receptor antagonist	Reduce oxidative stress	[13]
9	ABT-627	Endothelin A receptor (ETA) antagonist	Hinders the vasospasm activity of endothelin 1 (ET1) and nitric oxide synthesis	[54]
10	Zibotentan (ZD4054)	Endothelin A receptor antagonist or endothelin 1 receptor precursor antagonist	Improve cerebral artery blood flow or cerebral oxygenation indirectly	[5]
11	Ambrisentan	Endothelin receptor antagonists (ERAs)	Slow down pulmonary arterial hypertension progression in Alzheimer	[106]
12	Macitentan	Endothelin receptor antagonists (ERAs)	Slow down pulmonary arterial hypertension progression in Alzheimer	[106]