Venlafaxine
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Basic Info
Common Name | Venlafaxine(F04745) |
2D Structure | |
Description | Venlafaxine (brand name: Effexor or Efexor) is an effective antidepressant for many persons; Venlafaxine is a bicyclic antidepressant, and is usually categorized as a serotonin-norepinephrine reuptake inhibitor (SNRI), but it has been referred to as a serotonin-norepinephrine-dopamine reuptake inhibitor. It works by blocking the transporter reuptake proteins for key neurotransmitters affecting mood, thereby leaving more active neurotransmitter in the synapse. The neurotransmitters affected are serotonin (5-hydroxytryptamine) and norepinephrine (noradrenaline) Additionally, in high doses it weakly inhibits the reuptake of dopamine; A comparison of adverse event rates in a fixed dose study comparing venlafaxine 75, 225, and 375 mg/day with placebo revealed a dose dependency for some of the more common adverse events associated with venlafaxine use. The rule for including events was to enumerate those that occurred at an incidence of 5% or more for at least one of the venlafaxine groups and for which the incidence was at least twice the placebo incidence for at least one venlafaxine group. Tests for potential dose relationships for these events (Cochran-Armitage Test, with a criterion of exact 2-sided p-value <= 0.05) suggested a dose-dependency for several adverse events in this list, including chills, hypertension, anorexia, nausea, agitation, dizziness, somnolence, tremor, yawning, sweating, and abnormal ejaculation.[Wyeth Monograph]; Venlafaxine is an effective anti-depressant for many persons; however, it seems to be especially effective for those with treatment resistant depression. Some of these persons have taken two or more antidepressants prior to venlafaxine with no relief. Patients suffering with severe long-term depression typically respond better to venlafaxine than other drugs. However, venlafaxine has been reported to be more difficult to discontinue than other antidepressants. In addition, a September 2004 Consumer Reports study ranked venlafaxine as the most effective among six commonly prescribed antidepressants. However, this should not be considered a definitive finding, since responses to psychiatric medications can vary significantly from individual to individual; however, it seems to be especially effective for those with treatment-resistant depression. Some of these persons have taken two or more antidepressants prior to venlafaxine with no relief. Patients suffering with severe long term depression typically respond better to venlafaxine than other drugs. However, venlafaxine has been reported to be more difficult to discontinue than other antidepressants. In addition, a September 2004 Consumer Reports study ranked venlafaxine as the most effective among six commonly prescribed antidepressants. However, this should not be considered a definitive finding, since responses to psychiatric medications can vary significantly from individual to individual; Venlafaxine hydrochloride is a prescription antidepressant that belongs to the class of antidepressants called serotonin-norepinephrine reuptake inhibitors (SNRI). A Black Box Warning has been issued with Venlafaxine and with other SSRI and SNRI anti-depressants advising of risk of suicide. There is an additional risk if a physician misinterprets patient expression of adverse effects such as panic or akithesia. Careful assessment of patient history and comorbid risk factors such as drug abuse are essential in evaluating the safety of Venlafaxine for individual patients. Another risk is Serotonin syndrome. This is a serious effect that can be caused by interactions with other drugs and is potentially fatal. This risk necessitates clear information to patients and proper medical history. Venlafaxine is used primarily for the treatment of depression, generalized anxiety disorder, obsessive compulsive disorder, social anxiety disorder, and panic disorder in adults. It is also used for other general depressive disorders. Although it is not approved for use in children or adolescents, there is a considerable information by Wyeth on cautions if presecribed to this age group. Venlafaxine hydrochloride is a prescription antidepressant first introduced by Wyeth in 1993. It belongs to class of antidepressants called serotonin-norepinephrine reuptake inhibitors (SNRI). As of August 2006, generic venlafaxine is available in the United States. |
FRCD ID | F04745 |
CAS Number | 93413-69-5 |
PubChem CID | 5656 |
Formula | C17H27NO2 |
IUPAC Name | 1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl]cyclohexan-1-ol |
InChI Key | PNVNVHUZROJLTJ-UHFFFAOYSA-N |
InChI | InChI=1S/C17H27NO2/c1-18(2)13-16(17(19)11-5-4-6-12-17)14-7-9-15(20-3)10-8-14/h7-10,16,19H,4-6,11-13H2,1-3H3 |
Canonical SMILES | CN(C)CC(C1=CC=C(C=C1)OC)C2(CCCCC2)O |
Isomeric SMILES | CN(C)CC(C1=CC=C(C=C1)OC)C2(CCCCC2)O |
Wikipedia | Venlafaxine |
Synonyms | Venlafaxinum 1-(2-(dimethylamino)-1-(4-methoxyphenyl)ethyl)cyclohexanol venlafaxine 93413-69-5 Elafax Venlafaxina Venlafaxine [INN:BAN] D,L-Venlafaxine Venlafaxinum [INN-Latin] Venlafaxina [INN-Spanish] |
Classifies | Predicted: Pesticide |
Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
Kingdom | Organic compounds |
Superclass | Benzenoids |
Class | Phenol ethers |
Subclass | Anisoles |
Intermediate Tree Nodes | Not available |
Direct Parent | Anisoles |
Alternative Parents | |
Molecular Framework | Aromatic homomonocyclic compounds |
Substituents | Phenoxy compound - Anisole - Methoxybenzene - Alkyl aryl ether - Aralkylamine - Cyclohexanol - Monocyclic benzene moiety - 1,3-aminoalcohol - Tertiary alcohol - Cyclic alcohol - Tertiary aliphatic amine - Tertiary amine - Ether - Organic nitrogen compound - Organonitrogen compound - Organooxygen compound - Hydrocarbon derivative - Organopnictogen compound - Amine - Organic oxygen compound - Alcohol - Aromatic homomonocyclic compound |
Description | This compound belongs to the class of organic compounds known as anisoles. These are organic compounds containing a methoxybenzene or a derivative thereof. |
Properties
Property Name | Property Value |
---|---|
Molecular Weight | 277.408 |
Hydrogen Bond Donor Count | 1 |
Hydrogen Bond Acceptor Count | 3 |
Rotatable Bond Count | 5 |
Complexity | 279 |
Monoisotopic Mass | 277.204 |
Exact Mass | 277.204 |
XLogP | 2.9 |
Formal Charge | 0 |
Heavy Atom Count | 20 |
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+ | 0.9382 |
Human Intestinal Absorption | HIA+ | 0.9782 |
Caco-2 Permeability | Caco2+ | 0.8520 |
P-glycoprotein Substrate | Substrate | 0.6534 |
P-glycoprotein Inhibitor | Inhibitor | 0.7031 |
Inhibitor | 0.8031 | |
Renal Organic Cation Transporter | Non-inhibitor | 0.5792 |
Distribution | ||
Subcellular localization | Mitochondria | 0.8533 |
Metabolism | ||
CYP450 2C9 Substrate | Non-substrate | 0.7583 |
CYP450 2D6 Substrate | Substrate | 0.8919 |
CYP450 3A4 Substrate | Substrate | 0.7407 |
CYP450 1A2 Inhibitor | Non-inhibitor | 0.7664 |
CYP450 2C9 Inhibitor | Non-inhibitor | 0.6876 |
CYP450 2D6 Inhibitor | Inhibitor | 0.7287 |
CYP450 2C19 Inhibitor | Non-inhibitor | 0.7199 |
CYP450 3A4 Inhibitor | Non-inhibitor | 0.8308 |
CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.8666 |
Excretion | ||
Toxicity | ||
Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.5486 |
Inhibitor | 0.6627 | |
AMES Toxicity | Non AMES toxic | 0.8000 |
Carcinogens | Non-carcinogens | 0.6762 |
Fish Toxicity | High FHMT | 0.9363 |
Tetrahymena Pyriformis Toxicity | High TPT | 0.9345 |
Honey Bee Toxicity | High HBT | 0.5841 |
Biodegradation | Not ready biodegradable | 0.9941 |
Acute Oral Toxicity | III | 0.4700 |
Carcinogenicity (Three-class) | Non-required | 0.6563 |
Model | Value | Unit |
---|---|---|
Absorption | ||
Aqueous solubility | -3.4527 | LogS |
Caco-2 Permeability | 1.4594 | LogPapp, cm/s |
Distribution | ||
Metabolism | ||
Excretion | ||
Toxicity | ||
Rat Acute Toxicity | 2.5404 | LD50, mol/kg |
Fish Toxicity | 1.1128 | pLC50, mg/L |
Tetrahymena Pyriformis Toxicity | 0.6934 | pIGC50, ug/L |
References
Title | Journal | Date | Pubmed ID |
---|---|---|---|
Estimation of amount of selected pharmaceuticals sorbed onto digested sludge fromwastewater treatment plant Bratislava-Petržalka. | Environ Res | 2017 May | 28183039 |
Preliminary assessment on the bioaccessibility of contaminants of emergingconcern in raw and cooked seafood. | Food Chem Toxicol | 2017 Jun | 28202359 |
Aquatic concentrations of chemical analytes compared to ecotoxicity estimates. | Sci Total Environ | 2017 Feb 1 | 28040196 |
Zerovalent iron and iron(VI): Effective means for the removal of psychoactivepharmaceuticals and illicit drugs from wastewaters. | Sci Total Environ | 2016 Jan 1 | 26376114 |
A first screening and risk assessment of pharmaceuticals and additives inpersonal care products in waste water, sludge, recipient water and sediment from Faroe Islands, Iceland and Greenland. | Sci Total Environ | 2016 Aug 15 | 27092417 |
The influences of CYP2D6 genotypes and drug interactions on the pharmacokinetics of venlafaxine: exploring predictive biomarkers for treatment outcomes. | Psychopharmacology (Berl) | 2015 Jun | 25510856 |
Emerging contaminants (pharmaceuticals, personal care products, a food additiveand pesticides) in waters of Sydney estuary, Australia. | Mar Pollut Bull | 2015 Aug 15 | 26130525 |
Levomilnacipran for the treatment of major depressive disorder: a review. | Neuropsychiatr Dis Treat | 2015 | 25657584 |
Beneficial effects of fluoxetine, reboxetine, venlafaxine, and voluntary running exercise in stressed male rats with anxiety- and depression-like behaviors. | Behav Brain Res | 2013 Aug 1 | 23707245 |
Increased Cdk5/p35 activity in the dentate gyrus mediates depressive-likebehaviour in rats. | Int J Neuropsychopharmacol | 2012 Jul | 21682945 |
Regulation of brain-derived neurotrophic factor (BDNF) in the chronicunpredictable stress rat model and the effects of chronic antidepressanttreatment. | J Psychiatr Res | 2010 Oct | 20172535 |
The reductions in sweetened milk intake induced by interleukin-1 and endotoxin are not prevented by chronic antidepressant treatment. | Neuroimmunomodulation | 2001 | 11752890 |
Postnatal development of rats exposed to fluoxetine or venlafaxine during the third week of pregnancy. | Braz J Med Biol Res | 1999 Jan | 10347775 |
Differential effect of chronic antidepressant treatments on lipopolysaccharide-induced depressive-like behavioural symptoms in the rat. | Life Sci | 1999 | 10576557 |
Targets
- General Function:
- Serotonin receptor activity
- Specific Function:
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various alkaloids 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. Signaling inhibits adenylate cyclase activity.
- Gene Name:
- HTR1F
- Uniprot ID:
- P30939
- Molecular Weight:
- 41708.505 Da
References
- Bymaster FP, Dreshfield-Ahmad LJ, Threlkeld PG, Shaw JL, Thompson L, Nelson DL, Hemrick-Luecke SK, Wong DT: Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Neuropsychopharmacology. 2001 Dec;25(6):871-80. [11750180 ]
- General Function:
- Monoamine transmembrane transporter activity
- Specific Function:
- Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
- Gene Name:
- SLC6A3
- Uniprot ID:
- Q01959
- Molecular Weight:
- 68494.255 Da
References
- Dawson LA, Nguyen HQ, Geiger A: Effects of venlafaxine on extracellular concentrations of 5-HT and noradrenaline in the rat frontal cortex: augmentation via 5-HT1A receptor antagonism. Neuropharmacology. 1999 Aug;38(8):1153-63. [10462128 ]
- 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
- Mechanism of Action:
- Venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), inhibit the reuptake of both serotonin and norepinephrine with a potency greater for the 5-HT than for the NE reuptake process. Both venlafaxine and the ODV metabolite have weak inhibitory effects on the reuptake of dopamine but, unlike the tricyclics and similar to SSRIs, they are not active at histaminergic, muscarinic, or alpha(1)-adrenergic receptors.
References
- Mitchell HA, Ahern TH, Liles LC, Javors MA, Weinshenker D: The effects of norepinephrine transporter inactivation on locomotor activity in mice. Biol Psychiatry. 2006 Nov 15;60(10):1046-52. Epub 2006 Aug 7. [16893531 ]
- 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
- Mechanism of Action:
- Venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), inhibit the reuptake of both serotonin and norepinephrine with a potency greater for the 5-HT than for the NE reuptake process. Both venlafaxine and the ODV metabolite have weak inhibitory effects on the reuptake of dopamine but, unlike the tricyclics and similar to SSRIs, they are not active at histaminergic, muscarinic, or alpha(1)-adrenergic receptors.
References
- Beique J, de Montigny C, Blier P, Debonnel G: Effects of sustained administration of the serotonin and norepinephrine reuptake inhibitor venlafaxine: I. in vivo electrophysiological studies in the rat. Neuropharmacology. 2000 Jul 24;39(10):1800-12. [10884561 ]
- General Function:
- Thioesterase binding
- Specific Function:
- Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol.
- Gene Name:
- ADRA2A
- Uniprot ID:
- P08913
- Molecular Weight:
- 48956.275 Da
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [7855217 ]
- General Function:
- G-protein coupled acetylcholine receptor activity
- Specific Function:
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol.
- Gene Name:
- CHRM2
- Uniprot ID:
- P08172
- Molecular Weight:
- 51714.605 Da
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [7855217 ]
- 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. 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. Regulates the release of 5-hydroxytryptamine in the brain, and thereby affects neural activity. May also play a role in regulating the release of other neurotransmitters. May play a role in vasoconstriction.
- Gene Name:
- HTR1D
- Uniprot ID:
- P28221
- Molecular Weight:
- 41906.38 Da
References
- Millan MJ, Gobert A, Lejeune F, Newman-Tancredi A, Rivet JM, Auclair A, Peglion JL: S33005, a novel ligand at both serotonin and norepinephrine transporters: I. Receptor binding, electrophysiological, and neurochemical profile in comparison with venlafaxine, reboxetine, citalopram, and clomipramine. J Pharmacol Exp Ther. 2001 Aug;298(2):565-80. [11454918 ]
- 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
References
- Bymaster FP, Dreshfield-Ahmad LJ, Threlkeld PG, Shaw JL, Thompson L, Nelson DL, Hemrick-Luecke SK, Wong DT: Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Neuropsychopharmacology. 2001 Dec;25(6):871-80. [11750180 ]
- General Function:
- Receptor activity
- Specific Function:
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
- Gene Name:
- CHRM3
- Uniprot ID:
- P20309
- Molecular Weight:
- 66127.445 Da
References
- Stanton T, Bolden-Watson C, Cusack B, Richelson E: Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics. Biochem Pharmacol. 1993 Jun 9;45(11):2352-4. [8100134 ]
- General Function:
- Guanyl-nucleotide exchange factor activity
- Specific Function:
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase.
- Gene Name:
- CHRM4
- Uniprot ID:
- P08173
- Molecular Weight:
- 53048.65 Da
References
- Stanton T, Bolden-Watson C, Cusack B, Richelson E: Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics. Biochem Pharmacol. 1993 Jun 9;45(11):2352-4. [8100134 ]
- General Function:
- Peptide yy receptor activity
- Specific Function:
- Receptor for neuropeptide Y and peptide YY. The rank order of affinity of this receptor for pancreatic polypeptides is NPY > [Pro-34] PYY, PYY and [Leu-31, Pro-34] NPY > NPY (2-36) > [Ile-31, Gln-34] PP and PYY (3-36) > PP > NPY free acid.
- Gene Name:
- NPY1R
- Uniprot ID:
- P25929
- Molecular Weight:
- 44391.535 Da
References
- Bymaster FP, Dreshfield-Ahmad LJ, Threlkeld PG, Shaw JL, Thompson L, Nelson DL, Hemrick-Luecke SK, Wong DT: Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Neuropsychopharmacology. 2001 Dec;25(6):871-80. [11750180 ]
- 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:
- Venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), inhibit the reuptake of both serotonin and norepinephrine with a potency greater for the 5-HT than for the NE reuptake process. Both venlafaxine and the ODV metabolite have weak inhibitory effects on the reuptake of dopamine but, unlike the tricyclics and similar to SSRIs, they are not active at histaminergic, muscarinic, or alpha(1)-adrenergic receptors.
References
- Vaishnavi SN, Nemeroff CB, Plott SJ, Rao SG, Kranzler J, Owens MJ: Milnacipran: a comparative analysis of human monoamine uptake and transporter binding affinity. Biol Psychiatry. 2004 Feb 1;55(3):320-2. [14744476 ]
- General Function:
- Histamine receptor activity
- Specific Function:
- In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.
- Gene Name:
- HRH1
- Uniprot ID:
- P35367
- Molecular Weight:
- 55783.61 Da
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [7855217 ]
- 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
- Mechanism of Action:
- Venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), inhibit the reuptake of both serotonin and norepinephrine with a potency greater for the 5-HT than for the NE reuptake process. Both venlafaxine and the ODV metabolite have weak inhibitory effects on the reuptake of dopamine but, unlike the tricyclics and similar to SSRIs, they are not active at histaminergic, muscarinic, or alpha(1)-adrenergic receptors.
References
- David DJ, Bourin M, Hascoet M, Colombel MC, Baker GB, Jolliet P: Comparison of antidepressant activity in 4- and 40-week-old male mice in the forced swimming test: involvement of 5-HT1A and 5-HT1B receptors in old mice. Psychopharmacology (Berl). 2001 Feb;153(4):443-9. [11243491 ]
- General Function:
- Virus receptor activity
- Specific Function:
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and 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. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates phospholipase C and a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and promotes the release of Ca(2+) ions from intracellular stores. Affects neural activity, perception, cognition and mood. Plays a role in the regulation of behavior, including responses to anxiogenic situations and psychoactive substances. Plays a role in intestinal smooth muscle contraction, and may play a role in arterial vasoconstriction.(Microbial infection) Acts as a receptor for human JC polyomavirus/JCPyV.
- Gene Name:
- HTR2A
- Uniprot ID:
- P28223
- Molecular Weight:
- 52602.58 Da
- Mechanism of Action:
- Venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), inhibit the reuptake of both serotonin and norepinephrine with a potency greater for the 5-HT than for the NE reuptake process. Both venlafaxine and the ODV metabolite have weak inhibitory effects on the reuptake of dopamine but, unlike the tricyclics and similar to SSRIs, they are not active at histaminergic, muscarinic, or alpha(1)-adrenergic receptors.
References
- Ripoll N, Nic Dhonnchadha BA, Sebille V, Bourin M, Hascoet M: The four-plates test-retest paradigm to discriminate anxiolytic effects. Psychopharmacology (Berl). 2005 Jun;180(1):73-83. Epub 2005 Jan 26. [15918077 ]
- 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, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-iodophenyl-2-aminopropane (DOI) and 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. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelacortin neurons and the release of CRH that then regulates the release of corticosterone. Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress. Plays a role in insulin sensitivity and glucose homeostasis.
- Gene Name:
- HTR2C
- Uniprot ID:
- P28335
- Molecular Weight:
- 51820.705 Da
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [7855217 ]
- General Function:
- Phosphatidylinositol phospholipase c activity
- Specific Function:
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
- Gene Name:
- CHRM1
- Uniprot ID:
- P11229
- Molecular Weight:
- 51420.375 Da
References
- Stanton T, Bolden-Watson C, Cusack B, Richelson E: Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics. Biochem Pharmacol. 1993 Jun 9;45(11):2352-4. [8100134 ]
- General Function:
- Serotonin receptor activity
- Specific Function:
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various alkaloids 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. Signaling inhibits adenylate cyclase activity.
- Gene Name:
- HTR1E
- Uniprot ID:
- P28566
- Molecular Weight:
- 41681.57 Da
References
- Bymaster FP, Dreshfield-Ahmad LJ, Threlkeld PG, Shaw JL, Thompson L, Nelson DL, Hemrick-Luecke SK, Wong DT: Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Neuropsychopharmacology. 2001 Dec;25(6):871-80. [11750180 ]
- General Function:
- Serotonin receptor activity
- Specific Function:
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various ergot alkaloid derivatives 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. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of dopamine and 5-hydroxytryptamine release, 5-hydroxytryptamine uptake and in the regulation of extracellular dopamine and 5-hydroxytryptamine levels, and thereby affects neural activity. May play a role in the perception of pain. Plays a role in the regulation of behavior, including impulsive behavior. Required for normal proliferation of embryonic cardiac myocytes and normal heart development. Protects cardiomyocytes against apoptosis. Plays a role in the adaptation of pulmonary arteries to chronic hypoxia. Plays a role in vasoconstriction. Required for normal osteoblast function and proliferation, and for maintaining normal bone density. Required for normal proliferation of the interstitial cells of Cajal in the intestine.
- Gene Name:
- HTR2B
- Uniprot ID:
- P41595
- Molecular Weight:
- 54297.41 Da
References
- Bymaster FP, Dreshfield-Ahmad LJ, Threlkeld PG, Shaw JL, Thompson L, Nelson DL, Hemrick-Luecke SK, Wong DT: Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Neuropsychopharmacology. 2001 Dec;25(6):871-80. [11750180 ]