Cicletanine New insights into its pharmacological actions

Molecular Mechanisms Regulating the Vascular Prostacyclin Pathways and Their Adaptation during Pregnancy and in the Newborn

“…Some drugs may increase PGI 2 production by increasing PGIS activity. Cicletanine, an antihypertensive drug acting by increasing NO synthesis and blocking Ca 2ϩ channels, increases PGI 2 production possibly through activation of PGIS, stimulation of AA release, or increased cholesteryl ester hydrolase activity (Kalinowski et al, 1999). In addition, honokiol, a biphenyl neolignan in the cortex of Magnolia officinalis, has antithrombotic effects as a result of increased PGIS expression and inhibition of TXA 2 production (Zhang et al, 2007).…”

Cicletanine-induced hyponatremia and hypokalemia in kidney transplant patients

“…However, one possibility is a direct action on the vascular wall because cicletanine, a furopyridine-derivative drug, is believed to stimulate the synthesis of prostaglandin I 2 (also called prostacyclin) [5] and inhibit sympathetic nerve activity [10] . Another possibility is the natriuretic activity of the drug, resulting from the action of the sulfoconjugated metabolite of cicletanine [4] .…”

“…Cicletanine (Tenstaten; Daewoong, Seoul, Korea) is an antihypertensive agent, synthetized by Esanu et al in 1986, and has been widely used in European countries [4] . It has been commercially available in Korea since 1992 and is used for the treatment of hypertension because it has effects of natriuresis and vasodilation without reflex tachycardia [5] .…”

Near-Term Novel Therapies for PAH

“…Cicletanine has been in use for many years in Europe as a systemic antihypertensive. 12 Several potentially beneficial pharmacologic effects have been described: it stimulates vascular NO synthesis by enhancing the coupling (ie, dimerization) and thereby the activity of endothelial nitric oxide synthase (eNOS); it stimulates prostacyclin synthesis; it inhibits the cGMP phosphodiesterases 1 and 5; it has a calcium channel blocking effect via K + channel opening; it acts as a diuretic, natriuretic, and kaluretic. A recent case report from Dr Aaron Waxman's group at Harvard describes significant clinical benefit from cicletanine over a half-year period in a PAH patient that was failing other therapy, including a PDE-5 inhibitor.…”