Proteopedia - User contributions [en]

Januvia (sitagliptin)

2016-12-05T22:26:47Z

Matthew P Cabrera:

<applet load="" size="350" color="" frame="true" spin="on" Scene ="Sitagliptin/Sitagliptin/1" align="right" caption="Sitagliptin (Januvia), ([[1x70]])"/>

== Structural Highlights ==
Januvia is an aromatic compound with a terminal polar <scene name='74/745984/Tfp/3'>trifluorophenyl group</scene> and a <scene name='74/745984/Tfm/1'>trifluoromethyl group</scene>. The enzyme DPP-4 consists of a <scene name='Sitagliptin/Hdryo/1'>hydrophobic serine (S1) pocket</scene> and other <scene name='Sitagliptin/Hbond/2'>hydrogen bonding residues</scene>. Residues of importance for binding purposes between the enzyme DPP-4 and Januvia include the <scene name='Sitagliptin/Bound/1'>catalytic triad</scene> (Ser630, His740, and Asp708) and two glutamates (Glu205 and Glu206).<ref name= "PDB">Ghosh, S. & Goodsell, D. Dipeptidyl Peptidase 4: Protein Data Bank (PDB). (2016)
[http://dx.doi.org/10.2210/rcsb_pdb/mom_2016_10 doi:10.2210/rcsb_pdb/mom_2016_10]</ref>

== Function ==
Sitagliptin, more commonly known as Januvia, is a member of a class called dipeptidyl peptidase 4 (DPP-4) inhibitors, which has been approved for the therapy of type 2 diabetes.<ref name= "NIH">PMID: 17580730</ref><ref name= "EUROPA">Annex I: Summary of Product Characteristics, Januvia [Online] p 1-78. Merck Sharp & Dohme Ltd. http://ec.europa.eu/health/documents/community-register/2016/20160624135348/anx_135348_en.pdf (accessed Nov 12, 2016).</ref> Januvia is highly potent and a <scene name='Sitagliptin/Dpp4/2'>competitive inhibitor of the enzyme Dipeptidyl Peptidase-4 DPP-4</scene>.<ref name= "EUROPA" /> DPP-4 is an membrane-associated exopeptidase which plays a vital role in glucose metabolism. Januvia and other DPP-4 inhibitors allow the effects caused by the enzyme DPP-4 to be counteracted, thereby stimulating an increase in insulin secretion when hyperglycemia is present and inhibiting glucagon secretion.<ref name="NIH" /> These changes in insulin and glucagon levels can lead to lower hemoglobin A1c (HbA1c), fasting, and postprandial glucose concentrations, which alleviates many complications for individuals affected by type 2 diabetes with hyperglycemia.<ref name= "EUROPA" />

== Mechanism of Action ==
Incretin hormones, Glucagon-like peptide-1 (GLP-1) and Glucose-dependent insulinotropic polypeptide (GIP), are released by the intestine throughout the day and levels are increased in response to a meal.<ref name= "EUROPA" /> When blood glucose concentrations rise above normal levels, GLP-1 and GIP increase insulin secretion and release from pancreatic beta cells by intracellular signaling pathways involving cyclic AMP. In addition, GLP-1 also plays an important role reducing glucagon secretion from pancreatic alpha cells, delaying gastric emptying, and potential induction of satiety.<ref name="NIH" /> The activity of GLP-1 and GIP is limited by the enzyme Dipeptidyl Peptidase-4 (DPP-4).<ref name= "EUROPA" /> DPP-4 is an antigenic membrane serine exopeptidase that cleaves proline dipeptides from the N-terminal end of GLP-1 and GIP, rapidly hydrolyzing GLP-1 and GIP to produce inactive products. Januvia (Sitagliptin) is a <scene name='Sitagliptin/Dpp4/2'>competitive inhibitor of DPP-4</scene>, which prevents the enzymatic hydrolysis of GLP-1 and GIP by DPP-4.<ref name= "EUROPA" /> Thus, concentrations of the active forms of these incretin hormones are increased, which in turn increase insulin release and decrease glucagon levels by the pancreas in a glucose-dependent manner. Ultimately, these levels of insulin and glucagon result in a decrease in blood glucose levels. In individuals with type 2 diabetes, this lowering or normalization of blood glucose levels can be essential in alleviating major complications and improving overall quality of life. Januvia inhibits DPP-4 by binding to the <scene name='Sitagliptin/Dpp4/2'>active site of DPP-4</scene>, which consists of a <scene name='Sitagliptin/Hdryo/1'>hydrophobic serine (S1) pocket</scene> and other <scene name='Sitagliptin/Hbond/2'>hydrogen bonding residues</scene>. Januvia situates its trifluorophenyl group within the S1 hydrophobic pocket, forming four hydrogen bond interactions with the residues Glu 205, Glu 206, and Tyr 662, and burying its trifluoro group within a tight pocket formed by residues Ser 209 and Arg 358.<ref>doi:10.1021/jm0493156</ref>

<Structure load='1x70' size='300' frame='true' align='right' caption='Januvia Bound to DPP-4' scene='Insert optional scene name here' />

== Agonistic Effects ==
The incretin hormones GLP-1 and GIP are released by the intestine and signal the synthesis and release of insulin from pancreatic beta-cells.<ref name="NIH" /> Type 2 diabetes has been correlated to a progressive decline in beta-cell numbers and function, leading to insulin deficiency. DPP-4 inhibitors, such as Januvia, increase levels of active GLP-1 after a meal and reduces the glycemic parameters HbA1c, and fasting and postprandial glucose concentrations. Higher levels of GLP-1 have been shown to promote beta-cell proliferation and reduce the chance of beta-cell death.<ref name= "WILEY">doi:10.1111/j.1742-1241.2006.01178.x</ref> The preservation, neogenesis, or restoration of beta-cell function is vital in altering the progression of defective insulin secretions. Current research suggests Januvia and other DPP-4 inhibitors not only sustain glycemic control, but are also potentially involved in tissue repair, anti-inflammatory mechanisms, and the enhancement of immunotherapy in cancer treatment.<ref name= "OMEGA">Sarkar, M., et al. Double Edge Effect of DPP4 Inhibitor Sitagliptin, A Type-2 Anti-Diabetic Drug, on Inflammation, Injury and Cancer. (2016) J Stem Cell Regen Biol 2(3): 1- 7. [http://dx.doi.org/10.15436/2471-0598.16.017 doi:10.15436/2471-0598.16.017]</ref>

== Prolonged Treatment ==
Prolonged treatment of DPP-4 inhibitors has been linked to an increased risk in hypoglycemia, weight gain, as well as gastrointestinal side effects. DPP-4 inhibitors, prescribed to stabilize incretin hormones, also extend the action of hormones peptide YY, growth hormone-releasing hormone, neuropeptide Y, substance P and several chemokines. Prolonged exposure to these hormones may increase the risk of high blood pressure, neurogenic inflammation and allergic reactions.<ref name= "WILEY" />

== Possible Disease in Humans ==
Januvia has been linked to rheumatoid arthritis and various acute and chronic inflammatory diseases.<ref name= "OMEGA" /> Psoriasiform, an autoimmune skin inflammation, has also been observed in patients taking Januvia. Januvia can lead to low blood sugar, especially when used in conjunction with other medications that cause low blood sugar.<ref name ="FDA">Januvia (sitagliptin phosphate) Medication Guide [Online] 2013, p 1-4. U.S. Food and Drug Administration. http://www.fda.gov/downloads/drugs/drugsafety/ucm204269.pdf (accessed Nov 12, 2016).</ref> Common side effects involving Januvia include upper-respiratory infections, sore throat, and a stuffy or runny nose.<ref name ="FDA" /> After prolonged treatment, Januvia has been found to trigger pancreatitis, pancreatic and thyroid cancer.<ref name= "OMEGA" /> However, human origin cells did not show any indication of becoming cancerous.

== References ==
<references/>

Januvia (sitagliptin)

2016-12-05T22:24:30Z

Matthew P Cabrera:

<applet load="" size="350" color="" frame="true" spin="on" Scene ="Sitagliptin/Sitagliptin/1" align="right" caption="Sitagliptin (Januvia), ([[1x70]])"/>

== Structural Highlights ==
Januvia is an aromatic compound with a terminal polar <scene name='74/745984/Tfp/3'>trifluorophenyl group</scene> and a <scene name='74/745984/Tfm/1'>trifluoromethyl group</scene>. The enzyme DPP-4 consists of a <scene name='Sitagliptin/Hdryo/1'>hydrophobic serine (S1) pocket</scene> and other <scene name='Sitagliptin/Hbond/2'>hydrogen bonding residues</scene>. Residues of importance for binding purposes between the enzyme DPP-4 and Januvia include the <scene name='Sitagliptin/Bound/1'>catalytic triad</scene> (Ser630, His740, and Asp708) and two glutamates (Glu205 and Glu206).<ref name= "PDB">Ghosh, S. & Goodsell, D. Dipeptidyl Peptidase 4: Protein Data Bank (PDB). (2016)
[http://dx.doi.org/10.2210/rcsb_pdb/mom_2016_10 doi:10.2210/rcsb_pdb/mom_2016_10]</ref>

== Function ==
Sitagliptin, more commonly known as Januvia, is a member of a class called dipeptidyl peptidase 4 (DPP-4) inhibitors, which has been approved for the therapy of type 2 diabetes.<ref name= "NIH">PMID: 17580730</ref><ref name= "EUROPA">Annex I: Summary of Product Characteristics, Januvia [Online] p 1-78. Merck Sharp & Dohme Ltd. http://ec.europa.eu/health/documents/community-register/2016/20160624135348/anx_135348_en.pdf (accessed Nov 12, 2016).</ref> Januvia is highly potent and a <scene name='Sitagliptin/Dpp4/2'>competitive inhibitor of the enzyme Dipeptidyl Peptidase-4 DPP-4</scene>.<ref name= "EUROPA" /> DPP-4 is an membrane-associated exopeptidase which plays a vital role in glucose metabolism. Januvia and other DPP-4 inhibitors allow the effects caused by the enzyme DPP-4 to be counteracted, thereby stimulating an increase in insulin secretion when hyperglycemia is present and inhibiting glucagon secretion.<ref name="NIH" /> These changes in insulin and glucagon levels can lead to lower hemoglobin A1c (HbA1c), fasting, and postprandial glucose concentrations, which alleviates many complications for individuals affected by type 2 diabetes with hyperglycaemia.<ref name= "EUROPA" />

== Mechanism of Action ==
Incretin hormones, Glucagon-like peptide-1 (GLP-1) and Glucose-dependent insulinotropic polypeptide (GIP), are released by the intestine throughout the day and levels are increased in response to a meal.<ref name= "EUROPA" /> When blood glucose concentrations rise above normal levels, GLP-1 and GIP increase insulin secretion and release from pancreatic beta cells by intracellular signaling pathways involving cyclic AMP. In addition, GLP-1 also plays an important role reducing glucagon secretion from pancreatic alpha cells, delaying gastric emptying, and potential induction of satiety.<ref name="NIH" /> The activity of GLP-1 and GIP is limited by the enzyme Dipeptidyl Peptidase-4 (DPP-4).<ref name= "EUROPA" /> DPP-4 is an antigenic membrane serine exopeptidase that cleaves proline dipeptides from the N-terminal end of GLP-1 and GIP, rapidly hydrolyzing GLP-1 and GIP to produce inactive products. Januvia (Sitagliptin) is a <scene name='Sitagliptin/Dpp4/2'>competitive inhibitor of DPP-4</scene>, which prevents the enzymatic hydrolysis of GLP-1 and GIP by DPP-4.<ref name= "EUROPA" /> Thus, concentrations of the active forms of these incretin hormones are increased, which in turn increase insulin release and decrease glucagon levels by the pancreas in a glucose-dependent manner. Ultimately, these levels of insulin and glucagon result in a decrease in blood glucose levels. In individuals with type 2 diabetes, this lowering or normalization of blood glucose levels can be essential in alleviating major complications and improving overall quality of life. Januvia inhibits DPP-4 by binding to the <scene name='Sitagliptin/Dpp4/2'>active site of DPP-4</scene>, which consists of a <scene name='Sitagliptin/Hdryo/1'>hydrophobic serine (S1) pocket</scene> and other <scene name='Sitagliptin/Hbond/2'>hydrogen bonding residues</scene>. Januvia situates its trifluorophenyl group within the S1 hydrophobic pocket, forming four hydrogen bond interactions with the residues Glu 205, Glu 206, and Tyr 662, and burying its trifluoro group within a tight pocket formed by residues Ser 209 and Arg 358.<ref>doi:10.1021/jm0493156</ref>

<Structure load='1x70' size='300' frame='true' align='right' caption='Januvia Bound to DPP-4' scene='Insert optional scene name here' />

== Agonistic Effects ==
The incretin hormones GLP-1 and GIP are released by the intestine and signal the synthesis and release of insulin from pancreatic beta-cells.<ref name="NIH" /> Type 2 diabetes has been correlated to a progressive decline in beta-cell numbers and function, leading to insulin deficiency. DPP-4 inhibitors, such as Januvia, increase levels of active GLP-1 after a meal and reduces the glycemic parameters HbA1c, and fasting and postprandial glucose concentrations. Higher levels of GLP-1 have been shown to promote beta-cell proliferation and reduce the chance of beta-cell death.<ref name= "WILEY">doi:10.1111/j.1742-1241.2006.01178.x</ref> The preservation, neogenesis, or restoration of beta-cell function is vital in altering the progression of defective insulin secretions. Current research suggests Januvia and other DPP-4 inhibitors not only sustain glycemic control, but are also potentially involved in tissue repair, anti-inflammatory mechanisms, and the enhancement of immunotherapy in cancer treatment.<ref name= "OMEGA">Sarkar, M., et al. Double Edge Effect of DPP4 Inhibitor Sitagliptin, A Type-2 Anti-Diabetic Drug, on Inflammation, Injury and Cancer. (2016) J Stem Cell Regen Biol 2(3): 1- 7. [http://dx.doi.org/10.15436/2471-0598.16.017 doi:10.15436/2471-0598.16.017]</ref>

== Prolonged Treatment ==
Prolonged treatment of DPP-4 inhibitors has been linked to an increased risk in hypoglycemia, weight gain, as well as gastrointestinal side effects. DPP-4 inhibitors, prescribed to stabilize incretin hormones, also extend the action of hormones peptide YY, growth hormone-releasing hormone, neuropeptide Y, substance P and several chemokines. Prolonged exposure to these hormones may increase the risk of high blood pressure, neurogenic inflammation and allergic reactions.<ref name= "WILEY" />

== Possible Disease in Humans ==
Januvia has been linked to rheumatoid arthritis and various acute and chronic inflammatory diseases.<ref name= "OMEGA" /> Psoriasiform, an autoimmune skin inflammation, has also been observed in patients taking Januvia. Januvia can lead to low blood sugar, especially when used in conjunction with other medications that cause low blood sugar.<ref name ="FDA">Januvia (sitagliptin phosphate) Medication Guide [Online] 2013, p 1-4. U.S. Food and Drug Administration. http://www.fda.gov/downloads/drugs/drugsafety/ucm204269.pdf (accessed Nov 12, 2016).</ref> Common side effects involving Januvia include upper-respiratory infections, sore throat, and a stuffy or runny nose.<ref name ="FDA" /> After prolonged treatment, Januvia has been found to trigger pancreatitis, pancreatic and thyroid cancer.<ref name= "OMEGA" /> However, human origin cells did not show any indication of becoming cancerous.

== References ==
<references/>

5-hydroxytryptamine receptor

2016-11-10T22:24:28Z

Matthew P Cabrera:

<StructureSection load='4iar' size='350' side='right' scene='' caption='Human 5-hydroxytryptamine receptor 1B chimera with E. coli cytochrome B562 complex with ergotamine (PDB code [[4iar]]) '>
__TOC__
== Function ==

5-hydroxytryptamine (5-HT), Serotonin, receptors are found on the membrane of neurons in the central nervous system and peripheral nervous system. These receptors allow for the body to respond to serotonin and regulate many biological pathways. Serotonin, also known as 5 hydroxytryptamine, is an endogenous neurotransmitter made from tryptophan and is largely found in the gastrointestinal tract. It is known to regulate mood, appetite, digestion, circadian rhythm, learning and internal temperature regulation. It is can be an inhibitory or excitatory neurotransmitter that is released into the synaptic space and can bind to receptors on the postsynaptic neuron or be taken back up into the presynaptic neuron via Serotonin reuptake transporters.<ref>Goodsell D. ''Serotonin Receptor''. RCSB PDB-101 (2013) [http://www.rcsb.org/pdb/101/motm.do?momID=164 DOI: 10.2210/rcsb_pdb/mom_2013_8]</ref> 5-HT receptors are classified into 7 different subfamilies (5-HT1, 5-HT2, 5-HT3, etc.) by signaling mechanisms and homology of structure. All 5-HT receptors are known to have G-protein linked pathways except for the 5-HT3 receptor which acts as an ion channel. <ref name ="one">Wang C, Jiang Y, Ma J, Wu H, Wacker D, Katritch V, Han GW, Liu W, Huang XP, Vardy E, McCorvy JD, Gao X, Zhou EZ, Melcher K, Zhang C, Bai F, Yang H, Yang L, Jiang H, Roth BL, Cherezov V, Stevens RC, Xu HE. Structural Basis for Molecular Recognition at Serotonin Receptors. Science. 2013 May 3; 340(6132): 610–614. PMID:3644373 [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644373/]</ref>

== Structural highlights/Specific Function of 5-HT1B==
The <scene name='71/716548/5-ht1b/1'>5-HT1B receptor</scene> couples to G-protein alpha subunits Gi and Go. In the central nervous system, this receptor is an inhibitory presynaptic receptor that can alter the release of serotonin, as well as other neurotransmitters, from the presynaptic neuron. The structure of this receptor includes <scene name='71/716548/5-ht1b/6'>7 transmembrane alpha-helices</scene>.<scene name='71/716548/5-ht1b/8'>The N-terminal tail</scene> of 5-HT1B is close to the ligand binding pocket suggesting some interaction with its ligand. <scene name='71/716548/5-ht1b/9'>The ligand binding pocket</scene>, also called the orthosteric binding pocket, is characterized as a cavity formed from residues of the 3rd, 5th, 6th, and 7th alpha helices and the 2nd extracellular loop (ECL2). <ref name = "one" />

== Structural highlights/Specific Function of 5-HT2B==
The <scene name='71/716548/5-ht2b_receptor/1'>5-HT2B receptor</scene> is important in utilizing serotonin signals to encourage proper development and continuing function of the cardiovascular system. Overexpression of 5-HT2B has been linked to congestive heart failure.<ref>Wiebke J, Schymura Y, Novoyatleva T, Kojonazarov B, Boehm M, Wietelmann A, Luitel H, Murmann K, Krompiec DR, Tretyn A, Pullamsetti SS, Weissmann N, Seeger W, Ghofrani HA, Schermuly RT. 5-HT2B Receptor Antagonists Inhibit Fibrosis and Protect from RV Heart Failure. Biomed Res Int. 2015; 2015: 438403. PMID:4312574 [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4312574]</ref> 5-HT2B utilizes the alpha Gq protein pathway which triggers intracellular cGMP production through activation of nictric-oxidase synthase (NOS).<ref>Nebigil, Etienne, Schaerlinger, Hickel, Launay, Maroteaux. ''Developmentally Regulated Serotonin 5-HT2B Receptors.'' [http://www.sciencedirect.com/science/article/pii/S0736574801000223 DOI: 10.1016/S0736-5748(01)00022-3]</ref> This receptor is also known for being the target of the drug LSD, which is similar in structure to serotonin. <ref>Berumen LC, Rodriguez A, Miledi R, Gracia-Alcocer G. Serotonin Receptors in Hippocampus. ScientificWorldJournal. 2012;2012:823493. Epub 2012 May 2. PMID:3353568 [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3353568/]</ref> The structure of this receptor is much like that of 5-HT1B, however significant differences are seen in their binding pockets. The pocket of 5-HT1B is much broader than <scene name='71/716548/5-ht2b/1'>that of 5-HT2B</scene>, due to a 3 Å shift of the top of helix V. Perhaps this difference highlights a variation in serotonin affinity between the two families. The similar characteristics of the 5-HT1B and 5-HT2B receptor families consist of 7 alpha helices and the N-terminus sticking out into extracellular space. <ref name="one" />

== Structural highlights/Specific Function of 5-HT3==
<scene name='71/716548/5-ht3_receptor/1'>The 5-HT3 receptor</scene> is a pentameric cation-selective ion channel and plays a role in neuronal excitation to release neurotransmitters from the postsynaptic neuron. Opening of the cation channel causes an influx of sodium and calcium through the receptor pore leading to a membrane depolarization. Five receptor subunits, A to E, have been found in humans but only subunits A and B have been found in rodents. When experimentally expressed in a host, the 5-HT3 receptor is comprised of either A or AB subunits which can result in a homopentameric receptor or a heteropentameric receptor respectively. The A and B subunits are found throughout the brain in areas such as the hippocampus and amygdala. 5-HT3 is a transmembrane channel that is stimulated to open state by the interaction of the receptor with serotonin in the extracellular space.<ref>Hassaine G,Cedric D, Luigino G, Romain W, Menno BT, Ruud H, Alexandra G, Henning S, Takashi T, Aline D, Christophe M, Xiao-Dan L, Frederic P, Horst V, Hugues N. ''X-ray Structure of the Mouse Serotonin 5-HT3 Receptor. Nature 512.7514 (2014): 276-81.[http://www.nature.com/nature/journal/v512/n7514/full/nature13552.html DOI:10.1038/nature13552]</ref> The binding site is comprised of six loops from two adjacent subunits in the extracellular N-terminal domain. Loops A, B and C form the principal subunit and contain the <scene name='71/716548/5-ht3/1'>important side chains</scene> N128, W183 and Y234. Loops D, E and F form the complementary subunit of the binding site and contain the important side chains W90, Y143 and W195. The transmembrane region is comprised of multiple alpha helical structures and mediates ion flow and ion specificity.<ref name = two> Thompson AJ, Lummis SCR. 5-HT3 Receptors. Curr Pharm Des. 2006; 12(28): 3615–3630. PMID:2664614 [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2664614/]</ref> 
For more details see [[5-ht3a receptor]].

== 5HT-2B receptor agonists: Lysergic Acid Diethylamide (LSD)==
Lysergic Acid Diethylamide, more commonly known as LSD, is a highly potent hallucinogen and is derived from ergotamine, an ergopeptine whose structural skeleton is contained in a diverse range of alkaloids. LSD acts as a non-selective 5-HT receptor agonist, meaning it can bind with equal affinity to two or more sub-types of receptors. LSD actively binds in the <scene name='71/716548/5-ht2b/3'>orthosteric binding pocket</scene> to both the 5-HT1B and 5HT-2B receptors, suggesting a similar chemical structure and function between the two receptor families. The docking is stabilized by all the same residues involved in normal binding in the orthosteric pocket. Hydrogen bonding between the amino group of the 5-membered ring of LSD and the T140 residue of the 5-HT2B receptor, as well as hydrogen bonding between D135 and the other ergoline amino group stabilize the LSD in a similar fashion that 5-HT would bind to the receptor. <ref name = "one" />

==5-HT3 receptor antagonists==
5-HT3 antagonists have been predominantly used as an antiemetic drug in relieving treating symptoms such as nausea and vomiting for a cancer patient receiving chemotherapy. Three high affinity antagonist often used are granisetron, tropisteron and ondansetron. The common structure shared among 5-HT3 antagonists contains an amine with an aromatic ring system and a carbonyl group. <ref name = "two" /> Experimental homology modeling suggests that 5-HT3 antagonists have aromatic rings that form π-π interactions with the tyrosine, Y143 and tryptophan, W183, side chains of the 5-HT3 receptor. It is also theorized that the antagonist contain carbonyl groups which accept hydrogen bonds from serine, S227, side chain of the 5-HT3 receptor.<ref>Maksay G, Zsolt B, Miklós S. ''Binding Interactions of Antagonists with 5‐Hydroxytryptamine 3A Receptor Models.'' Journal of Receptors and Signal Transduction 23.2-3 (2003): 255-70. [http://www.tandfonline.com/doi/full/10.1081/RRS-120025568 DOI:10.1081/RRS-120025568]</ref> During the binding of granisteron to the 5-HT3 receptor, the aromatic rings sit within W183 and Y234 and an azabicyclic ring within W90 and F226 of the binding pocket.<ref name = "two" /> Once a 5-HT3 antagonist has bound to a 5-HT3 receptor, serotonin binding is inhibited.<ref>Brunton LL, Lazo JS, Parker KL. (2006). Goddman & Gilman's The Pharmacological Basis of Therapeutics. New York: McGraw-Hill. pp. 1000–3. ISBN 978-0-07-142280-2.</ref> 
For more details see [[5-ht3a receptor]].
</StructureSection>
==3D structures of 5-hydroxytryptamine receptor==
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
{{#tree:id=OrganizedByTopic|openlevels=0|

*5-HT 1B

**[[4iar]] – hHT1B/cytochrome b562 (mutant) + ergotamine - human 
**[[4iaq]] – hHT1B/cytochrome b562 (mutant) + hydroergotamine 

*5-HT 2B

**[[4nc3]] – hHT2B/cytochrome b562 (mutant) 
**[[4ib4]] – hHT2B/cytochrome b562 (mutant) + ergotamine 

*5-HT 3A

**[[4pir]] – mHT3A + VHH15 - mouse 
}}

==References==

<references />