Antiserotonergic properties of terguride in blood vessels, platelets, and valvular interstitial cells.

Serotonin (5-hydroxytryptamine; 5-HT) is involved in heart valve tissue fibrosis, pulmonary arterial fibrosis, and pulmonary hypertension. We aimed at characterizing the antiserotonergic properties of the ergot alkaloid derivative terguride [1,1-diethyl-3-(6-methyl-8α-ergolinyl)urea] by using functional receptor assays and valvular interstitial cell culture. Terguride showed no vasoconstrictor effect in porcine coronary arteries (5-HT(2A) receptor bioassay) and no relaxant effect in porcine pulmonary arteries (5-HT(2B) receptor bioassay).

The bulky N6 substituent of cabergoline is responsible for agonism of this drug at 5-hydroxytryptamine 5-HT2A and 5-HT2B receptors and thus is a determinant of valvular heart disease.

Fibrotic valvular heart disease (VHD) has been observed in patients with Parkinson's disease treated with dopamine receptor agonists such as pergolide and cabergoline. 5-Hydroxytryptamine(2B) receptor (5-HT(2B)R) agonism is the most likely cause, but other 5-HT receptors may also play a role in VHD. We aimed at characterizing the molecular fragment of cabergoline responsible for agonism at 5-HT(2B)R and 5-HT(2A)R.