Classify the 5HT receptors and give examples of pharmacological agents that affect them (60% of marks). Outline the pharmacology of ondansetron (40% of marks).
The 5HT (5 Hydroxytryptamine or serotonin) receptor is a monoamine neurotransmitter synthesized from tryptophan, and is an important receptorin the body.. It is found in the CNS, gastrointestinal tract, platelets and mast cells. There are 7 main receptor subtypes (GProtein coupled are 5HT1, 5HT2, 5HT4 and 5HT7 and ligand-gated ion channel 5HT3). Drugs may affect them by acting on serotonergic transmission (degradation inhibitors- MAOI e.g. selegiline, storage inhibitors- amphetamine, reuptake inhibitors- SSRI’s or tricyclic antidepressants), serotonin agonists(selective-5HT1B, 5HT1D e.g.triptans for migraine, non-selective, e.g. ergotamine), serotonin antagonists(ketanserin, clozapine, ondansetron).
Ondansetron is a commonly used anti-emetic. Candidates were expected to mention, that it is a selective antagonist at the 5HT3 receptor centrally and peripherally. To outline “pharmacology” it was also expected that answers would mention that it comes in a variety of formulations and to outline its fundamental pharmacokinetic properties.
It is remarkable that 45% of the trainees managed to pass this question, as there is roughly one gazillion different serotonin receptor subtypes. Wisely choosing not to go there would probably be the right move: instead, you could do what the college answer did, which is simply list the more important families, mention something about most of them being G-protein coupled receptors (except for 5-HT3), and then discuss serotonin neurotransmission broadly in terms of increased or decreased production or reuptake/degradation. This would probably be enough for an answer valued at only 60% of the total mark. Or, one could list all the receptor families and try to come up with drugs to cover each one, which is the much more painful option. Whichever path you choose, this table should have you covered
| Receptor | Distribution (role) | Pharmacological agents |
| Ligand-gated cation ion channels | ||
| 5-HT3 |
|
Antagonists:
|
| G-protein coupled receptors | ||
| 5-HT1 |
|
Agonists:
|
| 5-HT2 |
|
Agonists
Antagonists
|
| 5-HT4 |
|
Agonists:
|
| 5-HT5 |
|
Antagonists
|
| 5-HT6 |
|
Antagonists
|
| 5-HT7 |
|
|
| Nonselective effects | ||
| All 5-HT receptors | Increase serotonin synthesis |
|
| Decrease serotonin reuptake |
|
|
| Displace monoamines from storage in presynaptic vesicles |
|
|
| Decrease monoamine degradation |
|
|
| Nonselective receptor antagonists |
|
|
| Nonselective receptor agonists |
|
|
In case anybody is wondering where any of this information comes from, it was "xPharm: the Comprehensive Pharmacology Reference" (2009), by Ennam & Bylund. In this encyclopaedic work, each receptor subtype has its own short chapter.
Deka, Satyendra, et al. "Pharmacology of Serotonin and Its Receptors." Frontiers in Pharmacology of Neurotransmitters. Springer, Singapore, 2020. 183-212.
Rojas-Fernandez, Carlos H. "Can 5-HT 3 Antagonists Really Contribute to Serotonin Toxicity? A Call for Clarity and Pharmacological Law and Order." Drugs-real world outcomes 1.1 (2014): 3-5.
Camilleri, Michael. "Serotonin in the gastrointestinal tract." Current opinion in endocrinology, diabetes, and obesity 16.1 (2009): 53.