Ondansetron
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Basic Info
| Common Name | Ondansetron(F04771) |
| 2D Structure | |
| Description | Ondansetron is a well tolerated drug with few side effects. Headache, constipation, and dizziness are the most commonly reported side effects associated with its use. There have been no significant drug interactions reported with this drugs use. It is broken down by the hepatic cytochrome P450 system and it has little effect on the metabolism of other drugs broken down by this system; Ondansetron is a serotonin 5-HT3 receptor antagonist used mainly to treat nausea and vomiting following chemotherapy. Its effects are thought to be on both peripheral and central nerves. One part is to reduce the activity of the vagus nerve, which is a nerve that activates the vomiting center in the medulla oblongata, the other is a blockage of serotonin receptors in the chemoreceptor trigger zone. It does not have much effect on vomiting due to motion sickness. This drug does not have any effect on dopamine receptors or muscarinic receptors; A competitive serotonin type 3 receptor antagonist. It is effective in the treatment of nausea and vomiting caused by cytotoxic chemotherapy drugs, including cisplatin, and has reported anxiolytic and neuroleptic properties; Ondansetron (INN) is a serotonin 5-HT3 receptor antagonist used mainly to treat nausea and vomiting following chemotherapy. Its effects are thought to be on both peripheral and central nerves. One part is to reduce the activity of the vagus nerve, which is a nerve that activates the vomiting center in the medulla oblongata, the other is a blockage of serotonin receptors in the chemoreceptor trigger zone. It does not have much effect on vomiting due to motion sickness. This drug does not have any effect on dopamine receptors or muscarinic receptors. |
| FRCD ID | F04771 |
| CAS Number | 99614-02-5 |
| PubChem CID | 4595 |
| Formula | C18H19N3O |
| IUPAC Name | 9-methyl-3-[(2-methylimidazol-1-yl)methyl]-2,3-dihydro-1H-carbazol-4-one |
| InChI Key | FELGMEQIXOGIFQ-UHFFFAOYSA-N |
| InChI | InChI=1S/C18H19N3O/c1-12-19-9-10-21(12)11-13-7-8-16-17(18(13)22)14-5-3-4-6-15(14)20(16)2/h3-6,9-10,13H,7-8,11H2,1-2H3 |
| Canonical SMILES | CC1=NC=CN1CC2CCC3=C(C2=O)C4=CC=CC=C4N3C |
| Isomeric SMILES | CC1=NC=CN1CC2CCC3=C(C2=O)C4=CC=CC=C4N3C |
| Wikipedia | Ondansetron |
| Synonyms |
ondansetron
99614-02-5
Zofran
Zophren
Zudan
Zofran ODT
9-Methyl-3-((2-methyl-1H-imidazol-1-yl)methyl)-2,3-dihydro-1H-carbazol-4(9H)-one
Zuplenz
ondansetron (Zofran)
GR-38032F
|
| Classifies |
Predicted: Fungal Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Organoheterocyclic compounds |
| Class | Indoles and derivatives |
| Subclass | Carbazoles |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Carbazoles |
| Alternative Parents | |
| Molecular Framework | Aromatic heteropolycyclic compounds |
| Substituents | Carbazole - N-alkylindole - Indole - Aryl ketone - Aryl alkyl ketone - N-methylpyrrole - N-substituted imidazole - Substituted pyrrole - Benzenoid - Imidazole - Pyrrole - Azole - Vinylogous amide - Heteroaromatic compound - Ketone - Azacycle - Organic oxide - Organopnictogen compound - Organic nitrogen compound - Organooxygen compound - Organonitrogen compound - Organic oxygen compound - Hydrocarbon derivative - Aromatic heteropolycyclic compound |
| Description | This compound belongs to the class of organic compounds known as carbazoles. These are compounds containing a three ring system containing a pyrrole ring fused on either side to a benzene ring. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 293.37 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 2 |
| Rotatable Bond Count | 2 |
| Complexity | 440 |
| Monoisotopic Mass | 293.153 |
| Exact Mass | 293.153 |
| XLogP | 2.3 |
| Formal Charge | 0 |
| Heavy Atom Count | 22 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 1 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.9882 |
| Human Intestinal Absorption | HIA+ | 0.9941 |
| Caco-2 Permeability | Caco2+ | 0.8867 |
| P-glycoprotein Substrate | Substrate | 0.7019 |
| P-glycoprotein Inhibitor | Inhibitor | 0.5833 |
| Inhibitor | 0.8807 | |
| Renal Organic Cation Transporter | Inhibitor | 0.7955 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.6906 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.7456 |
| CYP450 2D6 Substrate | Substrate | 0.8918 |
| CYP450 3A4 Substrate | Substrate | 0.6470 |
| CYP450 1A2 Inhibitor | Inhibitor | 0.9107 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9071 |
| CYP450 2D6 Inhibitor | Inhibitor | 0.8932 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.9026 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.8309 |
| CYP Inhibitory Promiscuity | High CYP Inhibitory Promiscuity | 0.5954 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.7054 |
| Inhibitor | 0.7926 | |
| AMES Toxicity | Non AMES toxic | 0.5463 |
| Carcinogens | Non-carcinogens | 0.9676 |
| Fish Toxicity | High FHMT | 0.5909 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.7847 |
| Honey Bee Toxicity | Low HBT | 0.7740 |
| Biodegradation | Not ready biodegradable | 0.9884 |
| Acute Oral Toxicity | III | 0.6226 |
| Carcinogenicity (Three-class) | Non-required | 0.6432 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -3.0121 | LogS |
| Caco-2 Permeability | 1.6242 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.4555 | LD50, mol/kg |
| Fish Toxicity | 1.1397 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.4552 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Dietary and pharmacological treatment of abdominal pain in IBS. | Gut | 2017 May | 28232472 |
| Effect of Nigella sativa L. seed extract on cisplatin-induced delay in gastricemptying in Sprague-Dawley rats. | Nat Prod Res | 2017 Mar | 27348571 |
| Tranexamic acid induces kaolin intake stimulating a pathway involving tachykinin neurokinin 1 receptors in rats. | Eur J Pharmacol | 2014 Jan 15 | 24333477 |
| A case of abrin toxin poisoning, confirmed via quantitation of L-abrine (N-methyl-L-tryptophan) biomarker. | J Med Toxicol | 2014 Dec | 24522983 |
| Treatment of acute gastroenteritis in children: an overview of systematic reviewsof interventions commonly used in developed countries. | Evid Based Child Health | 2013 Jul | 23877938 |
| Review article: the management of acute gastroenteritis in children. | Aliment Pharmacol Ther | 2013 Feb | 23190209 |
| Formulation and in vivo evaluation of ondansetron orally disintegrating tabletsusing different superdisintegrants. | Arch Pharm Res | 2011 Nov | 22139694 |
| Rapid upregulation of sodium-glucose transporter SGLT1 in response to intestinal sweet taste stimulation. | Ann Surg | 2010 May | 20395849 |
| Gastroenteritis in children. | BMJ Clin Evid | 2009 Sep 23 | 21726481 |
| Ondansetron blocks LiCl-induced conditioned place avoidance but not conditionedtaste/flavor avoidance in rats. | Physiol Behav | 2009 Oct 19 | 19583975 |
| Pharmacological manipulation of immune-induced food aversion in rats. | Neuroimmunomodulation | 2009 Jan | 19077442 |
| Update on neuropharmacological treatments for alcoholism: scientific basis andclinical findings. | Biochem Pharmacol | 2008 Jan 1 | 17880925 |
| Delayed gastric emptying: whom to test, how to test, and what to do. | Curr Treat Options Gastroenterol | 2006 Jul | 16836948 |
| Serotonin-type 3 receptors mediate intestinal Polycose- and glucose-inducedsuppression of intake. | Am J Physiol Regul Integr Comp Physiol | 2005 Jun | 15718390 |
| Pharmacokinetics of tigecycline after single and multiple doses in healthysubjects. | Antimicrob Agents Chemother | 2005 Jan | 15616299 |
| Ondansetron and Delta-9-tetrahydrocannabinol interfere with the establishment of lithium-induced conditioned taste avoidance in the house musk shrew (Suncus murinus). | Behav Neurosci | 2005 Aug | 16187826 |
| Differential effects of selective vagotomy and tropisetron in aminoprivicfeeding. | Am J Physiol Regul Integr Comp Physiol | 2000 Sep | 10956259 |
| Efficacy of oral ondansetron, a selective antagonist of 5-HT3 receptors, in the treatment of nausea and vomiting associated with cyclophosphamide-based chemotherapies. Ondansetron Study Group. | Am J Clin Oncol | 1994 Apr | 8141105 |
| Pica in rats is analogous to emesis: an animal model in emesis research. | Pharmacol Biochem Behav | 1993 Aug | 8415820 |
| Food intake and rumen motility in dwarf goats. Effects of some serotonin receptoragonists and antagonists. | Vet Res Commun | 1992 | 1494862 |
Targets
- General Function:
- Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
- Specific Function:
- Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr). Isoforms USO have no channel activity by themself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin-dependent degradation.
- Gene Name:
- KCNH2
- Uniprot ID:
- Q12809
- Molecular Weight:
- 126653.52 Da
References
- Keseru GM: Prediction of hERG potassium channel affinity by traditional and hologram qSAR methods. Bioorg Med Chem Lett. 2003 Aug 18;13(16):2773-5. [12873512 ]
References
- Hibert MF, Hoffmann R, Miller RC, Carr AA: Conformation-activity relationship study of 5-HT3 receptor antagonists and a definition of a model for this receptor site. J Med Chem. 1990 Jun;33(6):1594-600. [2342053 ]
- General Function:
- Drug transmembrane transporter activity
- Specific Function:
- Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acyclovir, and ganciclovir. Responsible for the secretion of cationic drugs across the brush border membranes.
- Gene Name:
- SLC47A2
- Uniprot ID:
- Q86VL8
- Molecular Weight:
- 65083.915 Da
References
- Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM: Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem. 2013 Feb 14;56(3):781-95. doi: 10.1021/jm301302s. Epub 2013 Jan 22. [23241029 ]
- General Function:
- Ligand-gated ion channel activity
- Specific Function:
- After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane permeable to sodium ions.
- Gene Name:
- CHRNA4
- Uniprot ID:
- P43681
- Molecular Weight:
- 69956.47 Da
References
- Papke RL, Porter Papke JK, Rose GM: Activity of alpha7-selective agonists at nicotinic and serotonin 5HT3 receptors expressed in Xenopus oocytes. Bioorg Med Chem Lett. 2004 Apr 19;14(8):1849-53. [15050614 ]
- General Function:
- Serotonin receptor activity
- Specific Function:
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism. Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior. Plays a role in the response to anxiogenic stimuli.
- Gene Name:
- HTR1A
- Uniprot ID:
- P08908
- Molecular Weight:
- 46106.335 Da
References
- van Wijngaarden I, Tulp MT, Soudijn W: The concept of selectivity in 5-HT receptor research. Eur J Pharmacol. 1990 Jun 12;188(6):301-12. [2164935 ]
- General Function:
- Serotonin receptor activity
- Specific Function:
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive substances, such as lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. Arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Regulates the release of 5-hydroxytryptamine, dopamine and acetylcholine in the brain, and thereby affects neural activity, nociceptive processing, pain perception, mood and behavior. Besides, plays a role in vasoconstriction of cerebral arteries.
- Gene Name:
- HTR1B
- Uniprot ID:
- P28222
- Molecular Weight:
- 43567.535 Da
References
- van Wijngaarden I, Tulp MT, Soudijn W: The concept of selectivity in 5-HT receptor research. Eur J Pharmacol. 1990 Jun 12;188(6):301-12. [2164935 ]
- General Function:
- Serotonin receptor activity
- Specific Function:
- This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase.
- Gene Name:
- HTR4
- Uniprot ID:
- Q13639
- Molecular Weight:
- 43760.975 Da
References
- van Wijngaarden I, Tulp MT, Soudijn W: The concept of selectivity in 5-HT receptor research. Eur J Pharmacol. 1990 Jun 12;188(6):301-12. [2164935 ]
- General Function:
- Vitamin d3 25-hydroxylase activity
- Specific Function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599).
- Gene Name:
- CYP3A4
- Uniprot ID:
- P08684
- Molecular Weight:
- 57342.67 Da
References
- Yang Z, Fairfax DJ, Maeng JH, Masih L, Usyatinsky A, Hassler C, Isaacson S, Fitzpatrick K, DeOrazio RJ, Chen J, Harding JP, Isherwood M, Dobritsa S, Christensen KL, Wierschke JD, Bliss BI, Peterson LH, Beer CM, Cioffi C, Lynch M, Rennells WM, Richards JJ, Rust T, Khmelnitsky YL, Cohen ML, Manning DD: Discovery of 2-substituted benzoxazole carboxamides as 5-HT3 receptor antagonists. Bioorg Med Chem Lett. 2010 Nov 15;20(22):6538-41. doi: 10.1016/j.bmcl.2010.09.038. Epub 2010 Sep 16. [20889341 ]
- General Function:
- Toxin transporter activity
- Specific Function:
- Mediates potential-dependent transport of a variety of organic cations. May play a significant role in the disposition of cationic neurotoxins and neurotransmitters in the brain.
- Gene Name:
- SLC22A3
- Uniprot ID:
- O75751
- Molecular Weight:
- 61279.485 Da
References
- Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM: Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem. 2013 Feb 14;56(3):781-95. doi: 10.1021/jm301302s. Epub 2013 Jan 22. [23241029 ]
- General Function:
- Voltage-gated potassium channel activity
- Specific Function:
- This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor is a ligand-gated ion channel, which when activated causes fast, depolarizing responses in neurons. It is a cation-specific, but otherwise relatively nonselective, ion channel.
- Gene Name:
- HTR3A
- Uniprot ID:
- P46098
- Molecular Weight:
- 55279.835 Da
- Mechanism of Action:
- Ondansetron is a selective serotonin 5-HT<sub>3</sub> receptor antagonist. The serotonin 5-HT<sub>3</sub> receptors are located on the nerve terminals of the vagus in the periphery and centrally in the chemoreceptor trigger zone of the area postrema. It is thought that chemotherapeutic agents produce nausea and vomiting by releasing serotonin from the enterochromaffin cells of the small intestine, and that the released serotonin then activates 5-HT<sub>3</sub> receptors located on vagal efferents to initiate the vomiting reflex. Therefore Ondansetron works by blocking the reception of serotonin at these 5-HT<sub>3</sub> receptors.
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
- General Function:
- Monovalent cation:proton antiporter activity
- Specific Function:
- Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acyclovir, ganciclovir and also the zwitterionic cephalosporin, cephalexin and cephradin. Seems to also play a role in the uptake of oxaliplatin (a new platinum anticancer agent). Able to transport paraquat (PQ or N,N-dimethyl-4-4'-bipiridinium); a widely used herbicid. Responsible for the secretion of cationic drugs across the brush border membranes.
- Gene Name:
- SLC47A1
- Uniprot ID:
- Q96FL8
- Molecular Weight:
- 61921.585 Da
References
- Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM: Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem. 2013 Feb 14;56(3):781-95. doi: 10.1021/jm301302s. Epub 2013 Jan 22. [23241029 ]
- General Function:
- Secondary active organic cation transmembrane transporter activity
- Specific Function:
- Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin-dependent kinase II and LCK tyrosine kinase.
- Gene Name:
- SLC22A1
- Uniprot ID:
- O15245
- Molecular Weight:
- 61153.345 Da
References
- Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM: Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem. 2013 Feb 14;56(3):781-95. doi: 10.1021/jm301302s. Epub 2013 Jan 22. [23241029 ]
- General Function:
- Quaternary ammonium group transmembrane transporter activity
- Specific Function:
- Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity.
- Gene Name:
- SLC22A2
- Uniprot ID:
- O15244
- Molecular Weight:
- 62579.99 Da
References
- Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM: Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem. 2013 Feb 14;56(3):781-95. doi: 10.1021/jm301302s. Epub 2013 Jan 22. [23241029 ]
- General Function:
- Serotonin receptor activity
- Specific Function:
- This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase. It has a high affinity for tricyclic psychotropic drugs (By similarity). Controls pyramidal neurons migration during corticogenesis, through the regulation of CDK5 activity (By similarity). Is an activator of TOR signaling (PubMed:23027611).
- Gene Name:
- HTR6
- Uniprot ID:
- P50406
- Molecular Weight:
- 46953.625 Da
- Mechanism of Action:
- Ondansetron is a selective serotonin 5-HT<sub>3</sub> receptor antagonist. The serotonin 5-HT<sub>3</sub> receptors are located on the nerve terminals of the vagus in the periphery and centrally in the chemoreceptor trigger zone of the area postrema. It is thought that chemotherapeutic agents produce nausea and vomiting by releasing serotonin from the enterochromaffin cells of the small intestine, and that the released serotonin then activates 5-HT<sub>3</sub> receptors located on vagal efferents to initiate the vomiting reflex. Therefore Ondansetron works by blocking the reception of serotonin at these 5-HT<sub>3</sub> receptors.
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
- General Function:
- Voltage-gated calcium channel activity
- Specific Function:
- Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone. Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors. The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extend to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15. They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B. Also couples to adenylate cyclase stimulatory G alpha proteins. The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4. Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization. Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction. The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins. The activation of the ERK pathway occurs either in a G-protein-dependent or a beta-arrestin-dependent manner and is regulated by agonist-specific receptor phosphorylation. Acts as a class A G-protein coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling. Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling. Endogenous ligands induce rapid desensitization, endocytosis and recycling whereas morphine induces only low desensitization and endocytosis. Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties. Involved in neurogenesis. Isoform 12 couples to GNAS and is proposed to be involved in excitatory effects. Isoform 16 and isoform 17 do not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity.
- Gene Name:
- OPRM1
- Uniprot ID:
- P35372
- Molecular Weight:
- 44778.855 Da
References
- van Wijngaarden I, Tulp MT, Soudijn W: The concept of selectivity in 5-HT receptor research. Eur J Pharmacol. 1990 Jun 12;188(6):301-12. [2164935 ]