1983

Diuretic effect, Prostacyclin
1st PubMed, Lancet

1986

Launch in France
Robust safety profile (1983 - current)

> 10,000 clinical-trials patients
2 million post-launch patient years; serious adverse events rare (< 1 / 100,000 patient-months)

1989

CCL vs. salt - sensitive hypertension (SSH)

1991

CCL vs. SSH & sympathetic overdrive

1995

CCL vs. sympathetic overdrive

1996

Japan

Basal generation of nitric oxide (NO) in the vascular wall of Dahl S rats

2001

Japan, France, US

Papers report nitric oxide, antioxidant activity; improved endothelial function

2009

BK channel activity

(Unpublished research) Relevant to vascular aging, Alzheimer’s; patent filed, 2023

2013

Endothelial-function activity confirmed: eNOS activation

US research confirms eNOS and PKG activation

Where & When