Dextromethorphan
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Basic Info
| Common Name | Dextromethorphan(F04759) |
| 2D Structure | |
| Description | Dextromethorphan is an antitussive drug that is found in many over-the-counter cold and cough preparations, usually in the form of dextromethorphan hydrobromide. Dextromethorphan is a salt of the methyl ether dextrorotatory isomer of levorphanol, a narcotic analgesic. Dextromethorphan occurs as white crystals, is sparingly soluble in water, and freely soluble in alcohol. The drug is dextrorotatory in water (at 20 degrees Celsius, Sodium D-line) with a specific rotation of +27.6 degrees. Following oral administration, dextromethorphan is rapidly absorbed from the gastrointestinal tract, where it enters the bloodstream and crosses the blood-brain barrier. Dextromethorphan shows high affinity binding to several regions of the brain, including the medullary cough center. The first-pass through the hepatic portal vein results in some of the drug being metabolized into an active metabolite of dextromethorphan, dextrorphan, the 3-hydroxy derivative of dextromethorphan. The therapeutic activity of dextromethorphan is believed to be caused by both the drug and this metabolite. Dextromethorphan is predominantly metabolized by the liver, by various hepatic enzymes. Through various pathways, the drug undergoes (O-demethylation (which produces dextrorphan), N-demethylation, and partial conjugation with glucuronic acid and sulfate ions. The inactive metabolite (+)-3-hydroxy-N-methylmorphinan is formed as a product of DXM metabolism by these pathways. One well known metabolic catalyst involved is a specific cytochrome P450 enzyme known as 2D6, or CYP2D6. A significant portion of the population has a functional deficiency in this enzyme (and are known as poor CYP2D6 metabolizers). As CYP2D6 is the primary metabolic pathway in the inactivation of dextromethorphan, the duration of action and effects of dextromethorphan are significantly increased in such poor metabolizers. Deaths and hospitalizations have been reported in recreational use by poor CYP2D6 metabolizers. -- Wikipedia. This compound is an NMDA receptor antagonist (receptors, N-methyl-D-aspartate) and acts as a non-competitive channel blocker. It is also used to study the involvement of glutamate receptors in neurotoxicity. [PubChem] It is also the d-isomer of the codeine analog of levorphanol. Dextromethorphan shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is an NMDA receptor antagonist (receptors, N-methyl-D-aspartate) and acts as a non-competitive channel blocker. It is one of the widely used antitussives, and is also used to study the involvement of glutamate receptors in neurotoxicity. |
| FRCD ID | F04759 |
| CAS Number | 125-71-3 |
| PubChem CID | 5362449 |
| Formula | C18H25NO |
| IUPAC Name | None |
| InChI Key | MKXZASYAUGDDCJ-CGTJXYLNSA-N |
| InChI | InChI=1S/C18H25NO/c1-19-10-9-18-8-4-3-5-15(18)17(19)11-13-6-7-14(20-2)12-16(13)18/h6-7,12,15,17H,3-5,8-11H2,1-2H3/t15-,17+,18+/m0/s1 |
| Canonical SMILES | CN1CCC23CCCCC2C1CC4=C3C=C(C=C4)OC |
| Isomeric SMILES | CN1CC[C@]23CCCC[C@H]2[C@H]1CC4=C3C=C(C=C4)OC |
| Wikipedia | Dextromethorphan |
| Synonyms |
Methorphan
Levomethorphan [INN:BAN:DCF]
dextromethorphan
l-Methorphan
Levomethorphan
Levometorfano [INN-Spanish]
Levomethorphane [INN-French]
Levomethorphanum [INN-Latin]
UNII-7ZZ22K9QE6
(-)-3-Methoxy-N-methylmorphinan
|
| Classifies |
Predicted: Animal Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Alkaloids and derivatives |
| Class | Morphinans |
| Subclass | Not available |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Morphinans |
| Alternative Parents | |
| Molecular Framework | Aromatic heteropolycyclic compounds |
| Substituents | Morphinan - Phenanthrene - Benzazocine - Tetralin - Anisole - Alkyl aryl ether - Aralkylamine - Piperidine - Benzenoid - Tertiary aliphatic amine - Tertiary amine - Azacycle - Ether - Organoheterocyclic compound - Organopnictogen compound - Organic oxygen compound - Organooxygen compound - Organonitrogen compound - Organic nitrogen compound - Hydrocarbon derivative - Amine - Aromatic heteropolycyclic compound |
| Description | This compound belongs to the class of organic compounds known as morphinans. These are polycyclic compounds with a four-ring skeleton with three condensed six-member rings forming a partially hydrogenated phenanthrene moiety, one of which is aromatic while the two others are alicyclic. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 271.404 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 2 |
| Rotatable Bond Count | 1 |
| Complexity | 370 |
| Monoisotopic Mass | 271.194 |
| Exact Mass | 271.194 |
| XLogP | 3.4 |
| Formal Charge | 0 |
| Heavy Atom Count | 20 |
| Defined Atom Stereocenter Count | 3 |
| Undefined Atom Stereocenter Count | 0 |
| 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+ | 0.9989 |
| Human Intestinal Absorption | HIA+ | 0.9959 |
| Caco-2 Permeability | Caco2+ | 0.8867 |
| P-glycoprotein Substrate | Substrate | 0.8288 |
| P-glycoprotein Inhibitor | Inhibitor | 0.6540 |
| Non-inhibitor | 0.8383 | |
| Renal Organic Cation Transporter | Inhibitor | 0.7893 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.5052 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8187 |
| CYP450 2D6 Substrate | Substrate | 0.8919 |
| CYP450 3A4 Substrate | Substrate | 0.7783 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.9046 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9071 |
| CYP450 2D6 Inhibitor | Inhibitor | 0.8932 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.9025 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.8308 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.8673 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.7107 |
| Inhibitor | 0.6723 | |
| AMES Toxicity | Non AMES toxic | 0.5664 |
| Carcinogens | Non-carcinogens | 0.9616 |
| Fish Toxicity | High FHMT | 0.6059 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.5663 |
| Honey Bee Toxicity | Low HBT | 0.5846 |
| Biodegradation | Not ready biodegradable | 0.9763 |
| Acute Oral Toxicity | II | 0.7900 |
| Carcinogenicity (Three-class) | Non-required | 0.6932 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -2.2723 | LogS |
| Caco-2 Permeability | 1.4443 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 3.3377 | LD50, mol/kg |
| Fish Toxicity | 1.1386 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.7812 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: multidisciplinary care, symptom management, and cognitive/behavioral impairment (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. | Neurology | 2009 Oct 13 | 19822873 |
| Cytochrome P450 expression and related metabolism in human buccal mucosa. | Carcinogenesis | 2001 Mar | 11238190 |
| A massive outbreak of food poisoning--a reminder of the importance of proper toxic waste control. | S Afr Med J | 1996 May | 8711556 |
Targets
- General Function:
- Steroid hydroxylase activity
- Specific Function:
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
- Gene Name:
- CYP2D6
- Uniprot ID:
- P10635
- Molecular Weight:
- 55768.94 Da
References
- Venhorst J, ter Laak AM, Commandeur JN, Funae Y, Hiroi T, Vermeulen NP: Homology modeling of rat and human cytochrome P450 2D (CYP2D) isoforms and computational rationalization of experimental ligand-binding specificities. J Med Chem. 2003 Jan 2;46(1):74-86. [12502361 ]
- General Function:
- Protein phosphatase 2a binding
- Specific Function:
- NMDA receptor subtype of glutamate-gated ion channels with reduced single-channel conductance, low calcium permeability and low voltage-dependent sensitivity to magnesium. Mediated by glycine. May play a role in the development of dendritic spines. May play a role in PPP2CB-NMDAR mediated signaling mechanism (By similarity).
- Gene Name:
- GRIN3A
- Uniprot ID:
- Q8TCU5
- Molecular Weight:
- 125464.07 Da
- Mechanism of Action:
- Dextromethorphan is an opioid-like drug that binds to and acts as antagonist to the NMDA glutamatergic receptor, it is an agonist to the opioid sigma 1 and sigma 2 receptors, it is also an alpha3/beta4 nicotinic receptor antagonist and targets the serotonin reuptake pump. Dextromethorphan is rapidly absorbed from the gastrointestinal tract, where it enters the bloodstream and crosses the blood-brain barrier. The first-pass through the hepatic portal vein results in some of the drug being metabolized into an active metabolite of dextromethorphan, dextrorphan, the 3-hydroxy derivative of dextromethorphan.
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- Gene Name:
- SIGMAR1
- Uniprot ID:
- Q5T1J1
- Molecular Weight:
- 14852.655 Da
- Mechanism of Action:
- Dextromethorphan is an opioid-like drug that binds to and acts as antagonist to the NMDA glutamatergic receptor, it is an agonist to the opioid sigma 1 and sigma 2 receptors, it is also an alpha3/beta4 nicotinic receptor antagonist and targets the serotonin reuptake pump. Dextromethorphan is rapidly absorbed from the gastrointestinal tract, where it enters the bloodstream and crosses the blood-brain barrier. The first-pass through the hepatic portal vein results in some of the drug being metabolized into an active metabolite of dextromethorphan, dextrorphan, the 3-hydroxy derivative of dextromethorphan.
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Drug binding
- 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.
- Gene Name:
- CHRNA2
- Uniprot ID:
- Q15822
- Molecular Weight:
- 59764.82 Da
- Mechanism of Action:
- Dextromethorphan is an opioid-like drug that binds to and acts as antagonist to the NMDA glutamatergic receptor, it is an agonist to the opioid sigma 1 and sigma 2 receptors, it is also an alpha3/beta4 nicotinic receptor antagonist and targets the serotonin reuptake pump. Dextromethorphan is rapidly absorbed from the gastrointestinal tract, where it enters the bloodstream and crosses the blood-brain barrier. The first-pass through the hepatic portal vein results in some of the drug being metabolized into an active metabolite of dextromethorphan, dextrorphan, the 3-hydroxy derivative of dextromethorphan.
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Serotonin:sodium symporter activity
- Specific Function:
- Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.
- Gene Name:
- SLC6A4
- Uniprot ID:
- P31645
- Molecular Weight:
- 70324.165 Da
- Mechanism of Action:
- Dextromethorphan is an opioid-like drug that binds to and acts as antagonist to the NMDA glutamatergic receptor, it is an agonist to the opioid sigma 1 and sigma 2 receptors, it is also an alpha3/beta4 nicotinic receptor antagonist and targets the serotonin reuptake pump. Dextromethorphan is rapidly absorbed from the gastrointestinal tract, where it enters the bloodstream and crosses the blood-brain barrier. The first-pass through the hepatic portal vein results in some of the drug being metabolized into an active metabolite of dextromethorphan, dextrorphan, the 3-hydroxy derivative of dextromethorphan.
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Opioid receptor activity
- Specific Function:
- G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids. 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 leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain and in opiate-mediated analgesia. Plays a role in developing analgesic tolerance to morphine.
- Gene Name:
- OPRD1
- Uniprot ID:
- P41143
- Molecular Weight:
- 40368.235 Da
References
- Codd EE, Shank RP, Schupsky JJ, Raffa RB: Serotonin and norepinephrine uptake inhibiting activity of centrally acting analgesics: structural determinants and role in antinociception. J Pharmacol Exp Ther. 1995 Sep;274(3):1263-70. [7562497 ]
- General Function:
- Steroid binding
- Specific Function:
- Receptor for progesterone.
- Gene Name:
- PGRMC1
- Uniprot ID:
- O00264
- Molecular Weight:
- 21670.9 Da
References
- Chou YC, Liao JF, Chang WY, Lin MF, Chen CF: Binding of dimemorfan to sigma-1 receptor and its anticonvulsant and locomotor effects in mice, compared with dextromethorphan and dextrorphan. Brain Res. 1999 Mar 13;821(2):516-9. [10064839 ]
References
- Zhang W, Wang T, Qin L, Gao HM, Wilson B, Ali SF, Zhang W, Hong JS, Liu B: Neuroprotective effect of dextromethorphan in the MPTP Parkinson's disease model: role of NADPH oxidase. FASEB J. 2004 Mar;18(3):589-91. Epub 2004 Jan 20. [14734632 ]
- 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.
- Gene Name:
- CHRNA3
- Uniprot ID:
- P32297
- Molecular Weight:
- 57479.54 Da
References
- Damaj MI, Flood P, Ho KK, May EL, Martin BR: Effect of dextrometorphan and dextrorphan on nicotine and neuronal nicotinic receptors: in vitro and in vivo selectivity. J Pharmacol Exp Ther. 2005 Feb;312(2):780-5. Epub 2004 Sep 8. [15356218 ]
- 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
- Damaj MI, Flood P, Ho KK, May EL, Martin BR: Effect of dextrometorphan and dextrorphan on nicotine and neuronal nicotinic receptors: in vitro and in vivo selectivity. J Pharmacol Exp Ther. 2005 Feb;312(2):780-5. Epub 2004 Sep 8. [15356218 ]
- General Function:
- Toxic substance binding
- 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. The channel is blocked by alpha-bungarotoxin.
- Gene Name:
- CHRNA7
- Uniprot ID:
- P36544
- Molecular Weight:
- 56448.925 Da
References
- Damaj MI, Flood P, Ho KK, May EL, Martin BR: Effect of dextrometorphan and dextrorphan on nicotine and neuronal nicotinic receptors: in vitro and in vivo selectivity. J Pharmacol Exp Ther. 2005 Feb;312(2):780-5. Epub 2004 Sep 8. [15356218 ]
- 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 sodiun ions.
- Gene Name:
- CHRNB2
- Uniprot ID:
- P17787
- Molecular Weight:
- 57018.575 Da
References
- Damaj MI, Flood P, Ho KK, May EL, Martin BR: Effect of dextrometorphan and dextrorphan on nicotine and neuronal nicotinic receptors: in vitro and in vivo selectivity. J Pharmacol Exp Ther. 2005 Feb;312(2):780-5. Epub 2004 Sep 8. [15356218 ]
- 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.
- Gene Name:
- CHRNB4
- Uniprot ID:
- P30926
- Molecular Weight:
- 56378.985 Da
References
- Damaj MI, Flood P, Ho KK, May EL, Martin BR: Effect of dextrometorphan and dextrorphan on nicotine and neuronal nicotinic receptors: in vitro and in vivo selectivity. J Pharmacol Exp Ther. 2005 Feb;312(2):780-5. Epub 2004 Sep 8. [15356218 ]
- General Function:
- Norepinephrine:sodium symporter activity
- Specific Function:
- Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
- Gene Name:
- SLC6A2
- Uniprot ID:
- P23975
- Molecular Weight:
- 69331.42 Da
References
- Codd EE, Shank RP, Schupsky JJ, Raffa RB: Serotonin and norepinephrine uptake inhibiting activity of centrally acting analgesics: structural determinants and role in antinociception. J Pharmacol Exp Ther. 1995 Sep;274(3):1263-70. [7562497 ]
- General Function:
- Opioid receptor activity
- Specific Function:
- Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma membrane. Involved in the regulation of different receptors it plays a role in BDNF signaling and EGF signaling. Also regulates ion channels like the potassium channel and could modulate neurotransmitter release. Plays a role in calcium signaling through modulation together with ANK2 of the ITP3R-dependent calcium efflux at the endoplasmic reticulum. Plays a role in several other cell functions including proliferation, survival and death. Originally identified for its ability to bind various psychoactive drugs it is involved in learning processes, memory and mood alteration (PubMed:16472803, PubMed:9341151). Necessary for proper mitochondrial axonal transport in motor neurons, in particular the retrograde movement of mitochondria (By similarity).
- Gene Name:
- SIGMAR1
- Uniprot ID:
- Q99720
- Molecular Weight:
- 25127.52 Da
- Mechanism of Action:
- Dextromethorphan is an opioid-like drug that binds to and acts as antagonist to the NMDA glutamatergic receptor, it is an agonist to the opioid sigma 1 and sigma 2 receptors, it is also an alpha3/beta4 nicotinic receptor antagonist and targets the serotonin reuptake pump. Dextromethorphan is rapidly absorbed from the gastrointestinal tract, where it enters the bloodstream and crosses the blood-brain barrier. The first-pass through the hepatic portal vein results in some of the drug being metabolized into an active metabolite of dextromethorphan, dextrorphan, the 3-hydroxy derivative of dextromethorphan.
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Opioid receptor activity
- Specific Function:
- G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synthetic opioids and for the psychoactive diterpene salvinorin A. 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 leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain. Plays a role in mediating reduced physical activity upon treatment with synthetic opioids. Plays a role in the regulation of salivation in response to synthetic opioids. May play a role in arousal and regulation of autonomic and neuroendocrine functions.
- Gene Name:
- OPRK1
- Uniprot ID:
- P41145
- Molecular Weight:
- 42644.665 Da
References
- Codd EE, Shank RP, Schupsky JJ, Raffa RB: Serotonin and norepinephrine uptake inhibiting activity of centrally acting analgesics: structural determinants and role in antinociception. J Pharmacol Exp Ther. 1995 Sep;274(3):1263-70. [7562497 ]
- 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
- Codd EE, Shank RP, Schupsky JJ, Raffa RB: Serotonin and norepinephrine uptake inhibiting activity of centrally acting analgesics: structural determinants and role in antinociception. J Pharmacol Exp Ther. 1995 Sep;274(3):1263-70. [7562497 ]