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Record Information
Version2.0
Creation Date2009-07-21 20:27:05 UTC
Update Date2014-12-24 20:25:51 UTC
Accession NumberT3D2815
Identification
Common NameDextromethorphan
ClassSmall Molecule
DescriptionDextromethorphan 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.
Compound Type
  • Amine
  • Analgesic, Opioid
  • Antitussive Agent
  • Drug
  • Ether
  • Excitatory Amino Acid Antagonist
  • Food Toxin
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
Balminil DM
Bayer Select Flu Relief
Bayer Select Head & Chest Cold
Bayer Select Night Time Cold
Benylin DM
Benylin dm
Cerose-DM
Chloraseptic DM
Contac Day & Night Cold/Flu Day Caplets
Contac Jr. Non-drowsy Formula
Contac Nighttime Cold Medicine
Contac Severe Cold Formula Maximum Strength
Contac Severe Cold Formula Non-Drowsy
Coricidin Syrup
Cough-X
D-Methorphan
D-Methorphan Hydrobromide
Delsym
delta-Methorphan
Demorphan
Demorphan Hydrobromide
Demorphine
Destrometerfano
Dextromethorfan
Dextromethorphan Bromhydrate
Dextromethorphan Bromide
Dextromethorphan hydrobromide
Dextromethorphan hydrobromide monohydrate
Dextromethorphan hydrobromide OROS Tablets
Dextrométhorphane
Dextromethorphanum
Dextrometorfano
Dextrometorphan
Dextromorphan
Dexyromethorphan
Dimacol
Dimetapp DM
DM
DMHM
Drixoral Cough
Drixoral Cough & Congestion
Drixoral Cough & Sore Throat
DXM
Endotussin-NN
Endotussin-NN Pediatric
Hold
Koffex DM
L-Methorphan
Levomethorphan
Methorate
Naldecon-DX
Ornex Severe Cold Formula
Orthoxicol
PediaCare 1
PediaCare Cough-Cold Formula
Prestwick_686
Robitussin CF
Robitussin Cold & Cough
Robitussin Cough Calmers
Robitussin DM
Robitussin Maximum Strength Cough
Robitussin pediatric cough
Robitussin Pediatric Cough & Cold
Robitussin Pediatric Night Relief
Romilar
Rondec dm
Ru-Tuss Expectorant
St. Joseph Cough Syrup
Sudafed Cough Syrup
Triaminic
Trind-DM
Tussar DM
Tussi-Organidin
Tussi-Organidin DM NR
Tussi-Organidin DM-S NR
Tylenol Cold and Flu Multi-Symptom
Tylenol Cold and Flu No Drowsiness
Tylenol Cold No Drowsiness
Tylenol Cough + Decongestant Liquid
Tylenol Cough Liquid
Tylenol Flu No Drowsiness Gelcaps
Vicks Formula 44
Viro-Med
Chemical FormulaC18H25NO
Average Molecular Mass271.397 g/mol
Monoisotopic Mass271.194 g/mol
CAS Registry Number125-71-3
IUPAC Name(1R,9R,10R)-4-methoxy-17-methyl-17-azatetracyclo[7.5.3.0¹,¹⁰.0²,⁷]heptadeca-2(7),3,5-triene
Traditional Namelevomethorphan
SMILES[H][C@@]12CC3=C(C=C(OC)C=C3)[C@]3(CCCC[C@@]13[H])CCN2C
InChI IdentifierInChI=1/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+/s2
InChI KeyInChIKey=MKXZASYAUGDDCJ-HPAQEFICNA-N
Chemical Taxonomy
Description 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.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassMorphinans
Sub ClassNot Available
Direct ParentMorphinans
Alternative Parents
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
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point122-124°C
Boiling PointNot Available
Solubility74.7 mg/L
LogP3.6
Predicted Properties
PropertyValueSource
Water Solubility0.00851 mg/mLALOGPS
logP3.75ALOGPS
logP3.49ChemAxon
logS-4.5ALOGPS
pKa (Strongest Basic)9.85ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area12.47 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity82.56 m3·mol-1ChemAxon
Polarizability31.74 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MSsplash10-054o-0190000000-5d924eb9e80a3ad52d7bView in MoNA
GC-MSGC-MS Spectrum - EI-Bsplash10-0ab9-9640000000-22a67aaa9771bdc70ea1View in MoNA
GC-MSGC-MS Spectrum - EI-Bsplash10-0ab9-9640000000-22a67aaa9771bdc70ea1View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, N/A (Annotated)splash10-0006-2931000000-7ed39f5c12687bd18073View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, N/A (Annotated)splash10-001i-9450000000-484ef060149382ae3835View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, N/A (Annotated)splash10-004i-0296000000-9cc5da1af6297bf41d6aView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-0090000000-cdc95ffda5c8ab176bc0View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00di-0090000000-82ba173765c1d557ad82View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0udl-0190000000-f4f99127c0b1de038b01View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-0090000000-25cdbb74a0783952c40eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00di-0090000000-8062e3b60f2d8d6c78b9View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0btc-3290000000-e2bedc154835e1c44dbcView in MoNA
1D NMR1H NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
Toxicity Profile
Route of ExposureOral, rapidly absorbed from the gastrointestinal tract.
Mechanism of ToxicityDextromethorphan 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.
MetabolismHepatic. Rapidly and extensively metabolized to dextrorphan (active metabolite). One well known metabolic catalyst involved is a specific cytochrome P450 enzyme known as 2D6, or CYP2D6. Half Life: 3-6 hours
Toxicity ValuesLD50: 165 mg/kg (mice) (8) LD50: 350 mg/kg (rat) (8)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesThe primary use of dextromethorphan is as a cough suppressant, for the temporary relief of cough caused by minor throat and bronchial irritation (as commonly accompanies the common cold), as well as those resulting from inhaled irritants. In addition, a combination of dextromethorphan and quinidine has been shown to alleviate symptoms of easy laughing and crying (pseudobulbar affect) in patients with amyotrophic lateral sclerosis and multiple sclerosis.
Minimum Risk LevelNot Available
Health EffectsHypertension, shallow respiration. Dextromethorphan can cause other gastrointestinal disturbances. [Wikipedia]
Symptomssymptoms include vomitting, drowiness, diarrhea, urinary retention, fever, and sweating. [Wikipedia]
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00514
HMDB IDHMDB01920
PubChem Compound ID5362449
ChEMBL IDCHEMBL52440
ChemSpider ID4642423
KEGG IDC06947
UniProt IDNot Available
OMIM ID
ChEBI ID4470
BioCyc IDNot Available
CTD IDNot Available
Stitch IDDextromethorphan
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkDextromethorphan
References
Synthesis Reference

Mahendra R. Patel, “Sustained Release Suspension Preparation For Dextromethorphan.” U.S. Patent US20130115253, issued May 09, 2013.

MSDSLink
General References
  1. Brooks BR, Thisted RA, Appel SH, Bradley WG, Olney RK, Berg JE, Pope LE, Smith RA: Treatment of pseudobulbar affect in ALS with dextromethorphan/quinidine: a randomized trial. Neurology. 2004 Oct 26;63(8):1364-70. [15505150 ]
  2. Olney JW, Labruyere J, Price MT: Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs. Science. 1989 Jun 16;244(4910):1360-2. [2660263 ]
  3. Hargreaves RJ, Hill RG, Iversen LL: Neuroprotective NMDA antagonists: the controversy over their potential for adverse effects on cortical neuronal morphology. Acta Neurochir Suppl (Wien). 1994;60:15-9. [7976530 ]
  4. Carliss RD, Radovsky A, Chengelis CP, O'Neill TP, Shuey DL: Oral administration of dextromethorphan does not produce neuronal vacuolation in the rat brain. Neurotoxicology. 2007 Jul;28(4):813-8. Epub 2007 Apr 6. [17573115 ]
  5. Hernandez SC, Bertolino M, Xiao Y, Pringle KE, Caruso FS, Kellar KJ: Dextromethorphan and its metabolite dextrorphan block alpha3beta4 neuronal nicotinic receptors. J Pharmacol Exp Ther. 2000 Jun;293(3):962-7. [10869398 ]
  6. Tang YW, Rys PN, Rutledge BJ, Mitchell PS, Smith TF, Persing DH: Comparative evaluation of colorimetric microtiter plate systems for detection of herpes simplex virus in cerebrospinal fluid. J Clin Microbiol. 1998 Sep;36(9):2714-7. [9705419 ]
  7. Drugs.com [Link]
  8. IPCS Inchem monograph for Dextromethorphan [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.348 uMNot AvailableBindingDB 50366613
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Shin EJ, Nah SY, Chae JS, Bing G, Shin SW, Yen TP, Baek IH, Kim WK, Maurice T, Nabeshima T, Kim HC: Dextromethorphan attenuates trimethyltin-induced neurotoxicity via sigma1 receptor activation in rats. Neurochem Int. 2007 May;50(6):791-9. Epub 2007 Feb 4. [17386960 ]
  4. Shin EJ, Nah SY, Kim WK, Ko KH, Jhoo WK, Lim YK, Cha JY, Chen CF, Kim HC: The dextromethorphan analog dimemorfan attenuates kainate-induced seizures via sigma1 receptor activation: comparison with the effects of dextromethorphan. Br J Pharmacol. 2005 Apr;144(7):908-18. [15723099 ]
  5. Church AJ, Andrew RD: Spreading depression expands traumatic injury in neocortical brain slices. J Neurotrauma. 2005 Feb;22(2):277-90. [15716633 ]
  6. Arrington MP, Brown C, Schwartz CE: Synthesis of potent sigma-1 receptor ligands via fragmentation of dextromethorphan. Bioorg Med Chem Lett. 2004 Apr 5;14(7):1807-9. [15026077 ]
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC501.8 uMNot AvailableBindingDB 50366613
IC503.4 uMNot AvailableBindingDB 50366613
References
  1. 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 ]
  2. de Graaf C, Oostenbrink C, Keizers PH, van der Wijst T, Jongejan A, Vermeulen NP: Catalytic site prediction and virtual screening of cytochrome P450 2D6 substrates by consideration of water and rescoring in automated docking. J Med Chem. 2006 Apr 20;49(8):2417-30. [16610785 ]
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
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
General Function:
Not Available
Specific Function:
Not Available
Gene Name:
SIGMAR1
Uniprot ID:
Q5T1J1
Molecular Weight:
14852.655 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
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
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
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
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
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
  1. 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:
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
  1. 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
  1. 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 ]
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
  1. 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 ion channel activity
Specific Function:
Critical component of the membrane-bound oxidase of phagocytes that generates superoxide. It is the terminal component of a respiratory chain that transfers single electrons from cytoplasmic NADPH across the plasma membrane to molecular oxygen on the exterior. Also functions as a voltage-gated proton channel that mediates the H(+) currents of resting phagocytes. It participates in the regulation of cellular pH and is blocked by zinc.
Gene Name:
CYBB
Uniprot ID:
P04839
Molecular Weight:
65335.415 Da
References
  1. 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
  1. 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
  1. 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
  1. 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
  1. 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
  1. 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
  1. 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 ]