5-HT2b agonists are highly associated with cardiac valvulopathies, however, Lisuride - a 5-HT2b antagonist - is not associated with this effect, suggesting that stimulation of the 5-HT2b receptor can cause cardiac fibrosis. ^[1]

In blood, serotonin stored in platelets is active wherever platelets bind, as a vasoconstrictor to stop bleeding, and also as a fibrocyte mitotic, to aid healing. Because of these effects, overdoses of serotonin, or serotonin agonist drugs, may cause acute or chronic pulmonary hypertension from pulmonary vasoconstriction, or else syndromes of retroperitoneal fibrosis or cardiac valve fibrosis (endocardial fibrosis) from overstimulation of serotonic growth receptors on fibrocytes ^{[citation needed]}.

Serotonin itself may cause a syndrome of cardiac fibrosis when it is eaten in large quantities in the diet (the Matoki banana of East Africa) or when it is over-secreted by certain mid-gut carcinoid tumors ^{[2] [3]}

The valvular fibrosis in such cases is typically on the right side of the heart, since excess serotonin in the serum outside platelets is metabolized in the lungs, and does not reach the left circulation ^{[citation needed]}.

Serotonergic agonist drugs in overdose in experimental animals not only cause acute (and sometimes fatal) pulmonary hypertension, but there is epidemiologic evidence that chronic use of certain of these drugs produce a chronic pulmonary hypertensive syndrome in humans, also ^{[citation needed]}. Some serotinergic agonist drugs also cause fibrosis anywhere in the body, particularly the syndrome of retroperitoneal fibrosis, as well as right-sided cardiac valve fibrosis ^{[citation needed]}.

In the past, three groups of serotonergic drugs have been epidemiolgically linked with these syndromes. They are the serotonergic vasoconstrictive anti-migraine drugs (ergotamine and methysergide), the serotonergic appetite suppressant drugs (fenfluramine, chlorphentermine, and aminorex), and certain anti-parkinsonian dopaminergic agonists, which also stimulate serotonergic 5-HT_2B receptors ^{[citation needed]}. These include pergolide and cabergoline, but not the more specific lisuride ^{[citation needed]}. A number of these drugs have recently been withdrawn from the market after groups taking them showed a statistical increase of one or more off the side effects described ^{[citation needed]}.

Because neither the amino acid L-tryptophan nor the SSRI-class antidepressants raise blood serotonin levels ^{[citation needed]}, they are not under suspicion to cause the syndromes described. However, since 5-hydroxytryptophan (5-HTP) does raise blood serotonin levels, it is under some of the same scrutiny as actively serotonergic drugs ^{[citation needed]}.