The Effects of Selective Serotonin Reuptake Inhibitors on Motility of Peripheral Smooth Muscles

Abstract Selective serotonin reuptake inhibitors are chemically heterogeneous antidepressant drugs with small affinity for adrenergic, muscarinic and histaminergic receptors. This fact makes them one of the safest drugs among all antidepressants. However, the results of some experimental studies suggest that these antidepressants can modulate tone and spontaneous contractions of smooth muscle peripheral cells primarly by affecting the voltage-dependent ion channels. Fluoxetine causes relaxation of intestinal smooth muscle cells, contraction of gastric smooth muscle cells, and inhibition of muscular and neuronal nicotinic receptors, neuronal sodium channels, and voltage-dependent potassium channels on animal’s models. Paroxetine exhibits concentration-dependent stimulating effect on the spontaneous contractions of the isolated isthmus of human Fallopian tube. Citalopram induces contractions of the gastric fundus and the antrum, intestinal smooth muscle cell relaxation and has proarrhythmic effects due to blockage of Kv potassium channels. Escitalopram also blocks Kv channels of vascular smooth muscle cells of coronary arteries, as well as the hERG channels in the heart of rabbits, but it also shows concentration-dependent stimulating effect on the spontaneous contractions of the isolated ampulla of human Fallopian tube. Sertraline inhibits a wide range of heart ion channels including Kv channels on the vascular smooth muscles of rabbit coronary arteries. Fluvoxamine and dapoxetine also inhibit Kv channels of coronary arteries of rabbits, while at present there is no data on the effect of vilazodone and vortioxetine on peripheral smooth muscle cells. Knowledge of these peripheral effects of selective serotonin reuptake inhibitors could be of great importance in making treatment decisions for patients, such as in the case with paroxetine and escitalopram, which should be avoided in women of reproductive age due to the stimulating effect they have shown on spontaneous smooth muscle contractions of the human Fallopian tube.