Explore a selection of our essential drug information below, or:
Identification
- Generic Name
- Agmatine
- DrugBank Accession Number
- DB08838
- Background
Agmantine is a natural metabolite of the amino acid arginine. It is formed when arginine is decarboxylated by the enzyme arginine decarboxylase and is found naturally in ragweed pollen, ergot fungi, octopus muscle, herring sperm, sponges, and the mammalian brain. Agmatine is both an experimental and investigational drug. As an investigational drug, it is being studied in a non-blinded prospective case study in the United States looking at patients who have been diagnosed with small fiber peripheral neuropathy between the ages of 18 to 75 years. Up to now (July 2013), the results of this study have not yet been published. As an experimental drug, agmatine is being studied for several indications such as cardioprotection, diabetes, decreased kidney function, neuroprotection (stroke, severe CNS injuries, epilepsy, glaucoma, and neuropathic pain), and psychiatric conditions (depression, anxiety, schizophrenia, and cognition). The exact mechanism of action is still being investigated for all of the potential indications of agmatine.
- Type
- Small Molecule
- Groups
- Experimental
- Structure
Structure for Agmatine (DB08838)
- Weight
- Average: 130.1915
Monoisotopic: 130.121846468 - Chemical Formula
- C5H14N4
- Synonyms
- (4-aminobutyl) guanidine
- (4-aminobutyl)guanidine
- 1-amino-4-guanidobutane
- N-(4-aminobutyl)guanidine
- External IDs
- NSC-56332
Pharmacology
- Indication
Agmatine is being studied experimentally for several indications such as cardioprotection, diabetes, decreased kidney function, neuroprotection (stroke, severe CNS injuries, epilepsy, glaucoma, and neuropathic pain), and psychiatric conditions (depression, anxiety, schizophrenia, and cognition). As an investigational drug, agamatine is being studied in a non-blinded prospective case study in the United States looking at patients who have been diagnosed with small fiber peripheral neuropathy.
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Agmatine has several physiological effects. Its cardiovascular effects include mildly reducing heart rate and blood pressure. Also it promotes a mild hypoglycemic state, reduces cellular oxidative stress, and enhances glomerular filtration rate.
- Mechanism of action
The exact mechanism of action is still being investigated for all of the potential indications of agmatine. Some of the biochemical mechanisms discovered so far concern agmatine's indication for diabetes, neuroprotection, and psychiatric conditions. In diabetes, agmatine produces hypoglycemia by increasing the release of insulin form pancreatic islet cells and increasing glucose uptake by the cells through increased endorphin release from the adrenal glands. Concerning neuroprotection, agmatine's effects are thought to involve modulation of receptors (NMDA, alpha 2, and imidazoline) and ion channels (ATP sensitive potassium channels and voltage-gated calcium channels) as well as blocking nitric oxide synthesis. Agmatine blocks nitric oxide synthesis by reducing the nitric oxide synthase -2 (NOS-2) protein in astroglial cells and macrophages. With respect to agmatine's benefit in psychiatric disorders, it is suggested that the mechanism involves neurotransmitter receptor modulation of the NMDA, alpha-2, serotonin, opioid, and imidazoline receptors. Specifically when agmatine binds to the imidazoline and alpha 2 receptors, it acts as a neurotransmitter and releases catecholamines from the adrenal gland.
Target Actions Organism AAlpha-2C adrenergic receptor agonistHumans ANischarin agonistHumans AAcetylcholine receptor subunit alpha antagonistHumans AGlutamate receptor ionotropic, NMDA 1 antagonistHumans AATP-sensitive inward rectifier potassium channel 1 antagonistHumans AVoltage-dependent N-type calcium channel subunit alpha-1B antagonistHumans AAcid-sensing ion channel 3 agonistHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
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Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Agmatine can be increased when it is combined with Abametapir. Acarbose The risk or severity of hypoglycemia can be increased when Agmatine is combined with Acarbose. Acebutolol Acebutolol may increase the arrhythmogenic activities of Agmatine. Aceclofenac The risk or severity of hyperkalemia can be increased when Aceclofenac is combined with Agmatine. Acemetacin The risk or severity of hyperkalemia can be increased when Agmatine is combined with Acemetacin. - Food Interactions
- Not Available
Products
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Ingredient UNII CAS InChI Key Agmatine sulfate RU0176QL8I 2482-00-0 PTAYFGHRDOMJGC-UHFFFAOYSA-N
Categories
- Drug Categories
- Agents causing hyperkalemia
- Amidines
- Antiarrhythmic agents
- Anticholinergic Agents
- Bradycardia-Causing Agents
- Calcium Channel Blockers
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Guanidines
- Nicotinic Antagonists
- NMDA Receptor Antagonists
- OCT1 substrates
- OCT2 Substrates
- Vasodilating Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as guanidines. These are compounds containing a guanidine moiety, with the general structure (R1R2N)(R3R4N)C=N-R5.
- Kingdom
- Organic compounds
- Super Class
- Organic nitrogen compounds
- Class
- Organonitrogen compounds
- Sub Class
- Guanidines
- Direct Parent
- Guanidines
- Alternative Parents
- Carboximidamides / Organopnictogen compounds / Monoalkylamines / Imines / Hydrocarbon derivatives
- Substituents
- Aliphatic acyclic compound / Amine / Carboximidamide / Guanidine / Hydrocarbon derivative / Imine / Organopnictogen compound / Primary aliphatic amine / Primary amine
- Molecular Framework
- Aliphatic acyclic compounds
- External Descriptors
- guanidines, primary amino compound (CHEBI:17431) / Amines (C00179)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 70J407ZL5Q
- CAS number
- 306-60-5
- InChI Key
- QYPPJABKJHAVHS-UHFFFAOYSA-N
- InChI
- InChI=1S/C5H14N4/c6-3-1-2-4-9-5(7)8/h1-4,6H2,(H4,7,8,9)
- IUPAC Name
- N-(4-aminobutyl)guanidine
- SMILES
- NCCCCNC(N)=N
References
- General References
- Li G, Regunathan S, Barrow CJ, Eshraghi J, Cooper R, Reis DJ: Agmatine: an endogenous clonidine-displacing substance in the brain. Science. 1994 Feb 18;263(5149):966-9. [Article]
- Payandemehr B, Rahimian R, Bahremand A, Ebrahimi A, Saadat S, Moghaddas P, Fadakar K, Derakhshanian H, Dehpour AR: Role of nitric oxide in additive anticonvulsant effects of agmatine and morphine. Physiol Behav. 2013 Jun 13;118:52-7. doi: 10.1016/j.physbeh.2013.05.022. Epub 2013 May 14. [Article]
- Huang YC, Tzeng WS, Wang CC, Cheng BC, Chang YK, Chen HH, Lin PC, Huang TY, Chuang TJ, Lin JW, Chang CP: Neuroprotective effect of agmatine in rats with transient cerebral ischemia using MR imaging and histopathologic evaluation. Magn Reson Imaging. 2013 Sep;31(7):1174-81. doi: 10.1016/j.mri.2013.03.026. Epub 2013 May 1. [Article]
- Piletz JE, Aricioglu F, Cheng JT, Fairbanks CA, Gilad VH, Haenisch B, Halaris A, Hong S, Lee JE, Li J, Liu P, Molderings GJ, Rodrigues AL, Satriano J, Seong GJ, Wilcox G, Wu N, Gilad GM: Agmatine: clinical applications after 100 years in translation. Drug Discov Today. 2013 Sep;18(17-18):880-93. doi: 10.1016/j.drudis.2013.05.017. Epub 2013 Jun 13. [Article]
- Regunathan S, Piletz JE: Regulation of inducible nitric oxide synthase and agmatine synthesis in macrophages and astrocytes. Ann N Y Acad Sci. 2003 Dec;1009:20-9. [Article]
- O'Neil, Maryadele J. (2013). The Merck Index : An Encyclopedia of Chemicals, Drugs, and Biologicals (15th ed.). Royal Society of Chemistry, The. [ISBN:978-1849736701]
- External Links
- Human Metabolome Database
- HMDB0001432
- KEGG Compound
- C00179
- PubChem Compound
- 199
- PubChem Substance
- 175427116
- ChemSpider
- 194
- BindingDB
- 85213
- ChEBI
- 17431
- ChEMBL
- CHEMBL58343
- ZINC
- ZINC000001532560
- PDBe Ligand
- AG2
- Wikipedia
- Agmatine
- PDB Entries
- 1aq7 / 1mt1 / 1n13 / 2qqc / 2qqd / 3amu / 3au7 / 3iqd / 3n2o / 4xqe … show 17 more
- MSDS
- Download (125 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
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Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 234-238 degress Celcius From MSDS. - Predicted Properties
Property Value Source Water Solubility 3.61 mg/mL ALOGPS logP -1 ALOGPS logP -1.2 Chemaxon logS -1.6 ALOGPS pKa (Strongest Basic) 12.61 Chemaxon Physiological Charge 2 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 87.92 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 48.09 m3·mol-1 Chemaxon Polarizability 15.01 Å3 Chemaxon Number of Rings 0 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9113 Blood Brain Barrier + 0.8116 Caco-2 permeable + 0.576 P-glycoprotein substrate Substrate 0.5247 P-glycoprotein inhibitor I Non-inhibitor 0.9574 P-glycoprotein inhibitor II Non-inhibitor 0.6373 Renal organic cation transporter Inhibitor 0.5877 CYP450 2C9 substrate Non-substrate 0.8348 CYP450 2D6 substrate Substrate 0.609 CYP450 3A4 substrate Non-substrate 0.8303 CYP450 1A2 substrate Non-inhibitor 0.8126 CYP450 2C9 inhibitor Non-inhibitor 0.9396 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.9261 CYP450 3A4 inhibitor Non-inhibitor 0.9428 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9583 Ames test Non AMES toxic 0.7871 Carcinogenicity Non-carcinogens 0.8883 Biodegradation Not ready biodegradable 0.7355 Rat acute toxicity 2.7458 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8538 hERG inhibition (predictor II) Non-inhibitor 0.9246
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 130.7677999 predictedDarkChem Lite v0.1.0 [M-H]- 130.9257999 predictedDarkChem Lite v0.1.0 [M-H]- 130.8130999 predictedDarkChem Lite v0.1.0 [M-H]- 130.7004999 predictedDarkChem Lite v0.1.0 [M-H]- 131.42274 predictedDeepCCS 1.0 (2019) [M+H]+ 131.2823999 predictedDarkChem Lite v0.1.0 [M+H]+ 131.2673734 predictedDarkChem Standard v0.1.0 [M+H]+ 130.4169999 predictedDarkChem Lite v0.1.0 [M+H]+ 131.6278999 predictedDarkChem Lite v0.1.0 [M+H]+ 133.41353 predictedDeepCCS 1.0 (2019) [M+Na]+ 130.9847999 predictedDarkChem Lite v0.1.0 [M+Na]+ 130.9949999 predictedDarkChem Lite v0.1.0 [M+Na]+ 130.9827999 predictedDarkChem Lite v0.1.0 [M+Na]+ 130.8984999 predictedDarkChem Lite v0.1.0 [M+Na]+ 141.57024 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins
- Specific Function
- Alpha-2a adrenergic receptor binding
- Gene Name
- ADRA2C
- Uniprot ID
- P18825
- Uniprot Name
- Alpha-2C adrenergic receptor
- Molecular Weight
- 49521.585 Da
References
- Li G, Regunathan S, Barrow CJ, Eshraghi J, Cooper R, Reis DJ: Agmatine: an endogenous clonidine-displacing substance in the brain. Science. 1994 Feb 18;263(5149):966-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Acts either as the functional imidazoline-1 receptor (I1R) candidate or as a membrane-associated mediator of the I1R signaling. Binds numerous imidazoline ligands that induces initiation of cell-signaling cascades triggering to cell survival, growth and migration. Its activation by the agonist rilmenidine induces an increase in phosphorylation of mitogen-activated protein kinases MAPK1 and MAPK3 in rostral ventrolateral medulla (RVLM) neurons that exhibited rilmenidine-evoked hypotension (By similarity). Blocking its activation with efaroxan abolished rilmenidine-induced mitogen-activated protein kinase phosphorylation in RVLM neurons (By similarity). Acts as a modulator of Rac-regulated signal transduction pathways (By similarity). Suppresses Rac1-stimulated cell migration by interacting with PAK1 and inhibiting its kinase activity (By similarity). Also blocks Pak-independent Rac signaling by interacting with RAC1 and inhibiting Rac1-stimulated NF-kB response element and cyclin D1 promoter activation (By similarity). Inhibits also LIMK1 kinase activity by reducing LIMK1 'Tyr-508' phosphorylation (By similarity). Inhibits Rac-induced cell migration and invasion in breast and colon epithelial cells (By similarity). Inhibits lamellipodia formation, when overexpressed (By similarity). Plays a role in protection against apoptosis. Involved in association with IRS4 in the enhancement of insulin activation of MAPK1 and MAPK3. When overexpressed, induces a redistribution of cell surface ITGA5 integrin to intracellular endosomal structures
- Specific Function
- Alpha-tubulin binding
- Gene Name
- NISCH
- Uniprot ID
- Q9Y2I1
- Uniprot Name
- Nischarin
- Molecular Weight
- 166627.105 Da
References
- Li G, Regunathan S, Barrow CJ, Eshraghi J, Cooper R, Reis DJ: Agmatine: an endogenous clonidine-displacing substance in the brain. Science. 1994 Feb 18;263(5149):966-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Upon acetylcholine binding, 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
- Specific Function
- Acetylcholine binding
- Gene Name
- CHRNA1
- Uniprot ID
- P02708
- Uniprot Name
- Acetylcholine receptor subunit alpha
- Molecular Weight
- 51838.14 Da
References
- Loring RH: Agmatine acts as an antagonist of neuronal nicotinic receptors. Br J Pharmacol. 1990 Jan;99(1):207-11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:26875626, PubMed:26919761, PubMed:28105280, PubMed:28126851, PubMed:7685113). Sensitivity to glutamate and channel kinetics depend on the subunit composition (PubMed:26919761)
- Specific Function
- Amyloid-beta binding
- Gene Name
- GRIN1
- Uniprot ID
- Q05586
- Uniprot Name
- Glutamate receptor ionotropic, NMDA 1
- Molecular Weight
- 105371.945 Da
References
- Yang XC, Reis DJ: Agmatine selectively blocks the N-methyl-D-aspartate subclass of glutamate receptor channels in rat hippocampal neurons. J Pharmacol Exp Ther. 1999 Feb;288(2):544-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- In the kidney, probably plays a major role in potassium homeostasis. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. This channel is activated by internal ATP and can be blocked by external barium
- Specific Function
- Atp binding
- Gene Name
- KCNJ1
- Uniprot ID
- P48048
- Uniprot Name
- ATP-sensitive inward rectifier potassium channel 1
- Molecular Weight
- 44794.6 Da
References
- Shepherd RM, Hashmi MN, Kane C, Squires PE, Dunne MJ: Elevation of cytosolic calcium by imidazolines in mouse islets of Langerhans: implications for stimulus-response coupling of insulin release. Br J Pharmacol. 1996 Nov;119(5):911-6. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. This alpha-1B subunit gives rise to N-type calcium currents. N-type calcium channels belong to the 'high-voltage activated' (HVA) group. They are involved in pain signaling. Calcium channels containing alpha-1B subunit may play a role in directed migration of immature neurons. Mediates Ca(2+) release probability at hippocampal neuronal soma and synaptic terminals (By similarity)
- Specific Function
- Amyloid-beta binding
- Gene Name
- CACNA1B
- Uniprot ID
- Q00975
- Uniprot Name
- Voltage-dependent N-type calcium channel subunit alpha-1B
- Molecular Weight
- 262493.84 Da
References
- Weng XC, Gai XD, Zheng JQ, Li J: Agmatine blocked voltage-gated calcium channel in cultured rat hippocampal neurons. Acta Pharmacol Sin. 2003 Aug;24(8):746-50. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride. Generates a biphasic current with a fast inactivating and a slow sustained phase. In sensory neurons is proposed to mediate the pain induced by acidosis that occurs in ischemic, damaged or inflamed tissue. May be involved in hyperalgesia. May play a role in mechanoreception. Heteromeric channel assembly seems to modulate channel properties
- Specific Function
- Enterobactin transmembrane transporter activity
- Gene Name
- ASIC3
- Uniprot ID
- Q9UHC3
- Uniprot Name
- Acid-sensing ion channel 3
- Molecular Weight
- 58904.72 Da
References
- Li WG, Yu Y, Zhang ZD, Cao H, Xu TL: ASIC3 channels integrate agmatine and multiple inflammatory signals through the nonproton ligand sensing domain. Mol Pain. 2010 Dec 8;6:88. doi: 10.1186/1744-8069-6-88. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Uesawa Y, Takeuchi T, Mohri K: Integrated analysis on the physicochemical properties of dihydropyridine calcium channel blockers in grapefruit juice interactions. Curr Pharm Biotechnol. 2012 Jul;13(9):1705-17. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:11388889, PubMed:11408531, PubMed:12439218, PubMed:12719534, PubMed:15389554, PubMed:16263091, PubMed:16272756, PubMed:16581093, PubMed:19536068, PubMed:21128598, PubMed:23680637, PubMed:24961373, PubMed:34040533, PubMed:9187257, PubMed:9260930, PubMed:9655880). Functions as a pH- and Na(+)-independent, bidirectional transporter (By similarity). Cation cellular uptake or release is driven by the electrochemical potential (i.e. membrane potential and concentration gradient) and substrate selectivity (By similarity). Hydrophobicity is a major requirement for recognition in polyvalent substrates and inhibitors (By similarity). Primarily expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (By similarity). Most likely functions as an uptake carrier in enterocytes contributing to the intestinal elimination of organic cations from the systemic circulation (PubMed:16263091). Transports endogenous monoamines such as N-1-methylnicotinamide (NMN), guanidine, histamine, neurotransmitters dopamine, serotonin and adrenaline (PubMed:12439218, PubMed:24961373, PubMed:35469921, PubMed:9260930). Also transports natural polyamines such as spermidine, agmatine and putrescine at low affinity, but relatively high turnover (PubMed:21128598). Involved in the hepatic uptake of vitamin B1/thiamine, hence regulating hepatic lipid and energy metabolism (PubMed:24961373). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with lower efficency (PubMed:17460754). Also capable of transporting non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). May contribute to the transport of cationic compounds in testes across the blood-testis-barrier (Probable). Also involved in the uptake of xenobiotics tributylmethylammonium (TBuMA), quinidine, N-methyl-quinine (NMQ), N-methyl-quinidine (NMQD) N-(4,4-azo-n-pentyl)-quinuclidine (APQ), azidoprocainamide methoiodide (AMP), N-(4,4-azo-n-pentyl)-21-deoxyajmalinium (APDA) and 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:11408531, PubMed:15389554, PubMed:35469921, PubMed:9260930)
- Specific Function
- (r)-carnitine transmembrane transporter activity
- Gene Name
- SLC22A1
- Uniprot ID
- O15245
- Uniprot Name
- Solute carrier family 22 member 1
- Molecular Weight
- 61153.345 Da
References
- Grundemann D, Hahne C, Berkels R, Schomig E: Agmatine is efficiently transported by non-neuronal monoamine transporters extraneuronal monoamine transporter (EMT) and organic cation transporter 2 (OCT2). J Pharmacol Exp Ther. 2003 Feb;304(2):810-7. [Article]
- Winter TN, Elmquist WF, Fairbanks CA: OCT2 and MATE1 provide bidirectional agmatine transport. Mol Pharm. 2011 Feb 7;8(1):133-42. doi: 10.1021/mp100180a. Epub 2010 Dec 3. [Article]
- Molderings GJ, Bonisch H, Gothert M, Bruss M: Agmatine and putrescine uptake in the human glioma cell line SK-MG-1. Naunyn Schmiedebergs Arch Pharmacol. 2001 Jun;363(6):671-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:9260930, PubMed:9687576). Functions as a Na(+)-independent, bidirectional uniporter (PubMed:21128598, PubMed:9687576). Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (PubMed:15212162, PubMed:9260930, PubMed:9687576). However, may also engage electroneutral cation exchange when saturating concentrations of cation substrates are reached (By similarity). Predominantly expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (PubMed:15783073). Implicated in monoamine neurotransmitters uptake such as histamine, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, serotonin and tyramine, thereby supporting a physiological role in the central nervous system by regulating interstitial concentrations of neurotransmitters (PubMed:16581093, PubMed:17460754, PubMed:9687576). Also capable of transporting dopaminergic neuromodulators cyclo(his-pro), salsolinol and N-methyl-salsolinol, thereby involved in the maintenance of dopaminergic cell integrity in the central nervous system (PubMed:17460754). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Also transports guanidine and endogenous monoamines such as vitamin B1/thiamine, creatinine and N-1-methylnicotinamide (NMN) (PubMed:12089365, PubMed:15212162, PubMed:17072098, PubMed:24961373, PubMed:9260930). Mediates the uptake and efflux of quaternary ammonium compound choline (PubMed:9260930). Mediates the bidirectional transport of polyamine agmatine and the uptake of polyamines putrescine and spermidine (PubMed:12538837, PubMed:21128598). Able to transport non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). Also involved in the uptake of xenobiotic 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:12395288, PubMed:16394027). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
- Specific Function
- Acetylcholine transmembrane transporter activity
- Gene Name
- SLC22A2
- Uniprot ID
- O15244
- Uniprot Name
- Solute carrier family 22 member 2
- Molecular Weight
- 62579.99 Da
References
- Grundemann D, Hahne C, Berkels R, Schomig E: Agmatine is efficiently transported by non-neuronal monoamine transporters extraneuronal monoamine transporter (EMT) and organic cation transporter 2 (OCT2). J Pharmacol Exp Ther. 2003 Feb;304(2):810-7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:10196521, PubMed:10966924, PubMed:12538837, PubMed:17460754, PubMed:20858707). Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (PubMed:10966924). Functions as a Na(+)- and Cl(-)-independent, bidirectional uniporter (PubMed:12538837). Implicated in monoamine neurotransmitters uptake such as dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, histamine, serotonin and tyramine, thereby supporting a role in homeostatic regulation of aminergic neurotransmission in the brain (PubMed:10196521, PubMed:16581093, PubMed:20858707). Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with low efficiency (PubMed:17460754). May be involved in the uptake and disposition of cationic compounds by renal clearance from the blood flow (PubMed:10966924). May contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (Probable). Mediates the transport of polyamine spermidine and putrescine (By similarity). Mediates the bidirectional transport of polyamine agmatine (PubMed:12538837). Also transports guanidine (PubMed:10966924). May also mediate intracellular transport of organic cations, thereby playing a role in amine metabolism and intracellular signaling (By similarity)
- Specific Function
- Monoamine transmembrane transporter activity
- Gene Name
- SLC22A3
- Uniprot ID
- O75751
- Uniprot Name
- Solute carrier family 22 member 3
- Molecular Weight
- 61279.485 Da
References
- Grundemann D, Hahne C, Berkels R, Schomig E: Agmatine is efficiently transported by non-neuronal monoamine transporters extraneuronal monoamine transporter (EMT) and organic cation transporter 2 (OCT2). J Pharmacol Exp Ther. 2003 Feb;304(2):810-7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Heterodimer with SLC3A2, that functions as an antiporter which operates as an efflux route by exporting cationic amino acids from inside the cells in exchange with neutral amino acids plus sodium ions and may participate in nitric oxide synthesis via the transport of L-arginine (PubMed:10080182, PubMed:10655553, PubMed:14603368, PubMed:15756301, PubMed:15776427, PubMed:17329401, PubMed:9829974, PubMed:9878049). Also mediates arginine transport in non-polarized cells, such as monocytes, and is essential for the correct function of these cells (PubMed:15280038, PubMed:31705628). The transport mechanism is electroneutral and operates with a stoichiometry of 1:1 (By similarity). In vitro, Na(+) and Li(+), but also H(+), are cotransported with the neutral amino acids (By similarity)
- Specific Function
- Basic amino acid transmembrane transporter activity
- Gene Name
- SLC7A7
- Uniprot ID
- Q9UM01
- Uniprot Name
- Y+L amino acid transporter 1
- Molecular Weight
- 55990.01 Da
References
- Satriano J, Isome M, Casero RA Jr, Thomson SC, Blantz RC: Polyamine transport system mediates agmatine transport in mammalian cells. Am J Physiol Cell Physiol. 2001 Jul;281(1):C329-34. [Article]
Drug created at February 21, 2013 23:04 / Updated at August 02, 2024 07:31