Serotonin receptor antagonist explained

A serotonin antagonist, or serotonin receptor antagonist, is a drug used to inhibit the action of serotonin and serotonergic drugs at serotonin (5-HT) receptors.

Types

5-HT_2A antagonists

Antagonists of the 5-HT_2A receptor are sometimes used as atypical antipsychotics (contrast with typical antipsychotics, which are purely dopamine antagonists).

They include, but are not limited to:

• Cyproheptadine blocks 5-HT_2A, H1 and is a mild anticholinergic.
• Methysergide is a 5-HT_2A antagonist and nonselective 5-HT₁ receptor blocker. It causes retroperitoneal fibrosis and mediastinal fibrosis.
• Quetiapine blocks 5-HT_2A, 5-HT_1A, dopamine receptors D₁ and D₂, histamine receptor H1, and A1 adrenoreceptors.

5-HT_2A/2C antagonists

• Ketanserin Antihypertensive. Blocks 5-HT_2A, 5-HT_2C and Alpha 1 (A1) adrenoreceptors.
• Risperidone antipsychotic
• Trazodone
• Nefazodone

5-HT₃ antagonists

Another subclass consists of drugs selectively acting at the 5-HT₃ receptors, and thus are known as 5-HT₃ antagonists. They are efficacious in treating chemotherapy-induced emesis and postoperative nausea and vomiting.^[1]

They include, but are not limited to:

• Dolasetron
• Granisetron
• Ondansetron
• Palonosetron
• Tropisetron

Other 5-HT₃ antagonists have been considered for use in the treatment of irritable bowel syndrome:

• Alosetron
• Cilansetron

Also, the antidepressant mirtazapine acts as a 5-HT₃ antagonist.

Non-selective 5-HT antagonists

Although some non-selective serotonin antagonists may have a particular affinity for a specific 5-HT receptor (and thus may be listed below e.g., methysergide), they still may also possess a generalised non-selective action.

They include, but are not limited to:

• Chlorpromazine
• Cyproheptadine
• Metergoline
• Methysergide
• Mianserin
• Mirtazapine
• Oxetorone
• Pizotifen
• Propranolol
• Ritanserin
• Spiperone

Antihistamines with antiserotonergic activity

• Carbinoxamine
• Cinnarizine
• Cyproheptadine
• Hydroxyzine
• Methdilazine
• Pizotifen
• Promethazine
• Pizotifen is a 5-HT_2C antagonist, H1 blocker and anticholinergic useful in migraine prophylaxis. Also used in the treatment of migrane.
• Oxatomide
• Oxetorone Also used in the treatment of migrane.
• Ketotifen

Others

• Fenclonine (para-chlorophenylalanine; PCPA) An inhibitor of serotonin synthesis that has been used in the treatment of carcinoid syndrome.
• Feverfew^[2] Is a herb traditionally used for migraines (contains parthenolide^[3]).
• Reserpine Depletes serotonin stores in the brain, heart, and many other organs and has been used in hypertension and psychosis
• Gamma-mangostin from Garcinia mangostana^[4]

See also

• Serotonin receptor agonist

Notes and References

1. Lindley . C. . Blower . P. . Oral serotonin type 3-receptor antagonists for prevention of chemotherapy-induced emesis . American Journal of Health-System Pharmacy . 57 . 18 . 1685–1697 . 2000 . 11006796 . 10.1093/ajhp/57.18.1685. free .
2. Pittler MH, Ernst E . Max H . Pittler . Feverfew for preventing migraine . Cochrane Database of Systematic Reviews . 2004 . 1 . 10.1002/14651858.CD002286.pub2 . 14973986 . CD002286.
3. Mittra . S . Datta . A . Singh . SK . Singh . A . 5-Hydroxytryptamine-inhibiting property of Feverfew: role of parthenolide content . Acta Pharmacologica Sinica . December 2000 . 21 . 12 . 1106–14 . 11603284 .
4. Chairungsrilerd . Nattaya . Furukawa . K.-I. . Ohta . Tomihisa . Nozoe . Shigeo . Ohizumi . Yasushi . γ-Mangostin, a novel type of 5-hydroxytryptamine 2A receptor antagonist . Naunyn-Schmiedeberg's Archives of Pharmacology . 12 December 1997 . 357 . 1 . 25–31 . 10.1007/pl00005134 . 9459569 . 24972810 .