Related Experiment Video
Updated: Jul 14, 2026
12:21
Thermostabilization, Expression, Purification, and Crystallization of the Human Serotonin Transporter Bound to S-citalopram
Published on: November 27, 2016
Tegaserod inhibits the serotonin transporter SERT
Manfred G Ismair1, Gerd A Kullak-Ublick, Randy D Blakely
1Division of Gastroenterology and Hepatology, Department of Internal Medicine, University Hospital, Zurich, Switzerland.
Digestion
|May 19, 2007
Summary
Tegaserod, a treatment for irritable bowel syndrome, inhibits serotonin (SERT), dopamine (DAT), and norepinephrine (NET) transporters. This serotonin uptake inhibition may enhance its prokinetic effects through a synergistic mechanism with its known 5-HT4 receptor agonism.
Area of Science:
- Pharmacology
- Neuroscience
- Gastroenterology
Background:
- Tegaserod is a drug for constipation-predominant irritable bowel syndrome (IBS-C).
- Its prokinetic effect is attributed to 5-HT4 receptor agonism in the enteric nervous system.
- Potential interactions with serotonin (SERT), dopamine (DAT), and norepinephrine (NET) transporters were uninvestigated.
Purpose of the Study:
- To investigate tegaserod's inhibition of human SERT, DAT, and NET.
- To determine if tegaserod affects neurotransmitter reuptake transporters.
Main Methods:
- Tegaserod's inhibition of [3H]5-HT and [3H]dopamine uptake was measured in HEK 293 cells expressing hSERT, hDAT, and hNET.
- Comparison with untransfected control cells.
Main Results:
- Tegaserod inhibited SERT, DAT, and NET-mediated transport with IC50 values of 11.7, 20.7, and 3.2 µmol/L, respectively.
- Non-competitive inhibition of SERT-mediated 5-HT transport was observed with a Ki of 3.1 µmol/L.
- Negative controls (estrone-3-sulfate, taurocholic acid) did not inhibit hSERT.
Conclusions:
- Tegaserod acts as a serotonin uptake inhibitor, suggesting an additional mechanism of action.
- Inhibition of SERT and increased local 5-HT concentrations may contribute to tegaserod's prokinetic action.
- A synergistic effect between 5-HT4 agonism and SERT inhibition is proposed for tegaserod's efficacy.
Related Concept Videos
01:23Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists
Serotonin, a crucial neurotransmitter synthesized by enterochromaffin cells, plays a cardinal role in regulating gastrointestinal (GI) motility. With over 90% of the body's total serotonin in the GI tract, its influence on digestive processes is profound. Serotonin is swiftly released upon various stimuli, such as food boluses or certain drugs, triggering intrinsic sensory neurons in the myenteric plexus and extrinsic vagal and spinal sensory neurons. This leads to the activation of the...
01:21G-protein Coupled Receptors
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
01:23Antidepressant Drugs: MAOIs and Other Agents
Atypical antidepressants, including bupropion (Wellbutrin), mirtazapine (Remeron), nefazodone (Serzone), trazodone (Desyrel), and vilazodone (Viibryd), offer unique mechanisms of action. Bupropion weakly inhibits dopamine and norepinephrine reuptake, aiding depression treatment and smoking cessation, with a low risk of sexual dysfunction. Mirtazapine enhances serotonin and norepinephrine neurotransmission, leading to sedation, increased appetite, and weight gain. As a result, it helps treat...
01:28Antidepressant Drugs: Tricyclics, SSRIs, and SNRIs
Tricyclic Antidepressants (TCAs), including Desipramine (Norpramin), Imipramine (Tofranil), Clomipramine (Anafranil), and Amitriptyline (Elavil), inhibit serotonin and norepinephrine reuptake and also block other receptors. They are used for depression, pain conditions, and insomnia. Common adverse effects include anticholinergic effects, sedation, orthostatic hypotension, and weight gain. They have a narrow therapeutic window and so require plasma-level monitoring. Abrupt discontinuation can...
01:21Drugs Affecting Neurotransmitter Release or Uptake
Certain drugs can affect how neurotransmitters called catecholamines, are released or taken back up in the adrenergic neuron. They can have different effects on the body's sympathetic transmission. Reserpine, a natural compound found in the Rauwolfia shrub, blocks a transporter called vesicular monoamine transporter (VMAT), which leads to a buildup of catecholamines in the cell and reduces sympathetic transmission. Another drug called guanethidine works in multiple ways, including blocking...
01:28Drugs Affecting GI Tract Motility: Dopamine Receptor Antagonists
Prokinetic agents are specialized medications that stimulate gastrointestinal (GI) motility, promoting food movement through the GI tract. Dopamine, an inhibitory neurotransmitter, plays a significant role in this process, reducing GI motility and indirectly controlling the speed of digestion. Dopamine receptor antagonists, such as metoclopramide and domperidone, offer a unique advantage as prokinetic agents. By blocking the dopamine receptors, these drugs increase GI motility, improving food...