This pathology has also been seen in certain East-African tribes who eat foods (Matoke —a green banana) containing excess amounts of serotonin. Connection with direct serotonergic agonist drugs
Elevated prevalence of cardiac fibrosis and related valvopathies was found to be associated with use of a number of unrelated drugs following long-term statistical analysis once the drugs had been on the market for some time. The cause of this was unknown at the time, but eventually it was realised that all the implicated drugs acted as agonists at 5-HT2B receptors in the heart in addition to their intended sites of action elsewhere in the body.The precise mechanisms involved remain elusive however, as while the cardiotoxicity shows some dose–response relationship, it does not always develop, and consistent daily use over an extended period tends to be most strongly predictive of development of valvopathy.The drugs most classically associated with the condition are weight loss drugs such as fenfluramine and chlorphentermine, and antiparkinson drugs such as pergolide and cabergoline, which are prescribed for chronic use.The heart valve changes seen with moderate and intermittent use can result in permanent damage and life-threatening heart problems if use of the causative drug is increased or continued, however longitudinal studies of former patients suggest that the damage will heal over time to some extent at least.
Anorectics
Some appetite suppressant drugs such as fenfluramine (which in combination with phentermine was marketed as Pondimin and commonly referred to as fen-phen), chlorphentermine, and aminorex (along with its analogue 4-Methylaminorex which has seen sporadic use as a recreational drug) induce a similar pattern of cardiac fibrosis (and pulmonary hypertension), apparently by overstimulating 5HT2B receptors on the cardiac fibroblast cells.These drugs consequently tend to cause increased risk of heart valve damage and subsequent heart failure, which eventually led to them being withdrawn from the market. Antimigraine drugs
Certain antimigraine drugs which are targeted at serotonin receptors as vasoconstrictive agents, have long been known to be associated with pulmonary hypertension and Raynauds phenomenon (both vasoconstrictive effects), as well as retroperitoneal fibrosis (a fibrotic cell/fibrocyte proliferation effect, thought to be similar to cardiac valve fibrosis).These drugs include ergotamine and methysergide and both drugs can also cause cardiac fibrosis. Antiparkinson drugs
Certain antiparkinson drugs, although targeted at dopaminergic receptors, cross-react with serotoninergic 5-HT2B receptors as well, and have been reported to cause cardiac fibrosis. These drugs include pergolide and cabergoline. Antihypertensive drugs
Guanfacine may be a 5-HT2B agonist, based on the results of theoretical modeling and high-throughput screening. Pergolide
Pergolide was an antiparkinson medications that was in decreasing use since reported in 2003 to be associated with cardiac fibrosis. In March 2007, pergolide was withdrawn from the U.S. market due to serious valvular damage that was shown in two independent studies. Cabergoline
Like pergolide, cabergoline has been linked to cardiac damage.