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Identification
Name Clonidine
Accession Number DB00575 (APRD00174, DB07566)
Type small molecule
Groups approved
Description

Clonidine, an imidazoline-derivative hypotensive agent is a centrally-acting α2-adrenergic agonist. It crosses the blood-brain barrier and acts in the hypothalamus to induce a decrease in blood pressure. It may also be administered as an epidural infusion as an adjunct treatment in the management of severe cancer pain that is not relieved by opiate analgesics alone. Clonidine may be used for differential diagnosis of pheochromocytoma in hypertensive patients. Other uses for clonidine include prophylaxis of vascular migraine headaches, treatment of severe dysmenorrhea, management of vasomotor symptoms associated with menopause, rapid detoxification in the management of opiate withdrawal, treatment of alcohol withdrawal used in conjunction with benzodiazepines, management of nicotine dependence, topical use to reduce intraocular pressure in the treatment of open-angle and secondary glaucoma and hemorrhagic glaucoma associated with hypertension, and in the treatment of attention-deficit hyperactivity disorder (ADHD). Clonidine also exhibits some peripheral activity.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Chlornidinum
  • Clonidin
  • Clonidine HCl
  • Clonidinhydrochlorid
  • Clonidinum [INN-Latin]
  • ST 155BS
Brand names
  • Adesipress
  • Catapres
  • Catapres-TTS
  • Catapresan
  • Catapressan
  • Catarpres
  • Catarpresan
  • Clonistada
  • Dixarit
  • Duraclon
  • Duraclont
  • Ipotensium
  • Isoglaucon
  • Tenso-Timelets
Brand name mixtures
  • Combipres 0.1/15 Tab (Chlorthalidone + Clonidine Hydrochloride)
Categories
  • Antihypertensive Agents
  • Analgesics
  • Sympatholytics
  • Adrenergic alpha-Agonists
  • Central Alpha-Agonists
CAS number 4205-90-7
Weight Average: 230.094
Monoisotopic: 229.017352717
Chemical Formula C9H9Cl2N3
InChI Key InChIKey=GJSURZIOUXUGAL-UHFFFAOYSA-N
InChI
InChI=1S/C9H9Cl2N3/c10-6-2-1-3-7(11)8(6)14-9-12-4-5-13-9/h1-3H,4-5H2,(H2,12,13,14)
Plain Text
IUPAC Name
N-(2,6-dichlorophenyl)-4,5-dihydro-1H-imidazol-2-amine
SMILES
ClC1=CC=CC(Cl)=C1NC1=NCCN1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzene and Derivatives
  • Halobenzenes
  • Anilines
Substructures
  • Imidazolines
  • Benzene and Derivatives
  • Aryl Halides
  • Halobenzenes
  • Imidazoles
  • Heterocyclic compounds
  • Guanidines
  • Aromatic compounds
  • Carboxamidines
  • Anilines
Pharmacology
Indication May be used as an adjunct in the treatment of hypertension, as an epidural infusion as an adjunct treatment in the management of severe cancer pain that is not relieved by opiate analgesics alone, for differential diagnosis of pheochromocytoma in hypertensive patients, prophylaxis of vascular migraine headaches, treatment of severe dysmenorrhea, management of vasomotor symptoms associated with menopause, rapid detoxification in the management of opiate withdrawal, treatment of alcohol withdrawal used in conjunction with benzodiazepines, management of nicotine dependence, topical use to reduce intraocular pressure in the treatment of open-angle and secondary glaucoma and hemorrhagic glaucoma associated with hypertension, and in the treatment of attention-deficit hyperactivity disorder (ADHD).
Pharmacodynamics Clonidine is an α-adrenergic agent that acts specifically on α2-receptors. α2-receptors regulate a number of signaling pathways mediated by multiple Gi proteins, Gαi1, Gαi2, and G&alphai3. Stimulation of α2-receptors mediates effects such as inhibition of adenylyl cyclase, stimulation fo phospholipase D, stimulation of mitogen-activated protein kinases, stimulation of K+ currents and inhibition of Ca2+ currents. Three G-protein coupled α2-receptor subtypes have been identified: α2A, α2B, and α2C. Each subtype has a unique pattern of tissue distribution in the central nervous system and peripheral tissues. The α2A-receptor is widely distributed throughout the central nervous system; it is found in the locus coeruleus, brain stem nuclei, cerebral cortex, septum, hypothalamus, and hippocampus. α2A-receptors are also expressed in the kidneys, spleen, thymus, lung and salivary glands. The α2C-receptor is primarily expressed in the central nervous system, including the striatum, olfactory tubercle, hippocampus and cerebral cortex. Low levels of the α2C-subtype are also found in the kidneys. The α2B-receptor is located primarily in the periphery (kidney, liver, lung and heart) with low levels of expression in the thalamic nuclei of the central nervous system. The α2A- and α2C-receptors are located presynaptically and inhibit the released of noradrenaline from sympathetic nerves. Stimulation of these receptors decreases sympathetic tone, resulting in decreases in blood pressure and heart rate. Sedation and analgesia is mediated by centrally located α2A-receptors, while peripheral α2B-receptors mediate constriction of vascular smooth muscle. α2A-Receptors also mediate essential components of the analgesic effect of nitrous oxide in the spinal cord. Clonidine stimulates all three α2-receptor subtypes with similar potency. Its actions in the nervous system decreases blood pressure in patients with hypertension and decreases sympathetic overactivity in patients undergoing opioid withdrawal. Clonidine is also a potent sedative and analgesic and can prevent post-operative shivering in intensive and post-operative care. Its use in differential diagnosis of pheochromocytoma owes to the fact that hypertension in patients with pheochromocytoma is refractory to antihypertensive treatment with clonidine.
Mechanism of action See Pharmacology section above.
Absorption Well absorbed following oral administration. Bioavailability following chronic administration is approximately 65%.
Volume of distribution Not Available
Protein binding 20-40%, primarily to albumin
Metabolism

Hepatic. Metabolized via minor pathways. The major metabolite, p-hydroxyclonidine, is present in concentrations less than 10% of those of unchanged clonidine in urine. Four metabolites have been detected, but only p-hydroxyclonidine has been identified.

Enzyme Metabolite Reaction Km Vmax
Cytochrome P450 3A5 4-hydroxyclonidine 4-hydroxylation
Cytochrome P450 2D6 4-hydroxyclonidine 4-hydroxylation
Cytochrome P450 1A2 4-hydroxyclonidine 4-hydroxylation
Cytochrome P450 3A4 4-hydroxyclonidine 4-hydroxylation
Cytochrome P450 1A1 4-hydroxyclonidine 4-hydroxylation
Route of elimination Not Available
Half life 6-20 hours; 40-60% is excreted in urine unchanged, 20% is excreted in feces. Less than 10% is excreted by p-hydroxyclonidine.
Clearance Not Available
Toxicity Oral LD50 is 150 mg/kg in rat and 30 mg/kg in dog. Symptoms of overdose include constriction of pupils of the eye, drowsiness, high blood pressure followed by a drop in pressure, irritability, low body temperature, slowed breathing, slowed heartbeat, slowed reflexes, and weakness.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Boehringer ingelheim
  • Aveva drug delivery systems inc
  • Mylan technologies inc
  • Tris pharma inc
  • Pharmaforce inc
  • Bioniche pharma usa llc
  • Actavis elizabeth llc
  • American therapeutics inc
  • Dava pharmaceuticals inc
  • Duramed pharmaceuticals inc sub barr laboratories inc
  • Impax laboratories inc
  • Interpharm inc
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Par pharmaceutical inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Unichem laboratories ltd
  • Vintage pharmaceuticals llc
  • Warner chilcott div warner lambert co
  • Watson laboratories inc
  • Shionogi pharma inc
Packagers
Dosage forms
Form Route Strength
Injection, solution Epidural 100 mcg/ml
Injection, solution, concentrate Epidural 500 mcg/ml
Patch Transdermal 0.1 mg/24 hours
Patch Transdermal 0.2 mg/24 hours
Patch Transdermal 0.3 mg/24 hours
Tablet Oral 0.025 mg
Tablet Oral 0.1 mg
Tablet Oral 0.2 mg
Tablet Oral 0.3 mg
Prices
Unit description Cost Unit
Catapres-TTS-3 4 0.3 mg/24hr Patches Box 328.42 USD box
CloNIDine HCl 4 0.3 mg/24hr Patches Box 279.9 USD box
Catapres-TTS-2 4 0.2 mg/24hr Patches Box 236.75 USD box
CloNIDine HCl 4 0.2 mg/24hr Patches Box 201.75 USD box
Catapres-TTS-1 4 0.1 mg/24hr Patches Box 141.08 USD box
CloNIDine HCl 4 0.1 mg/24hr Patches Box 119.84 USD box
Catapres-tts 3 patch 78.95 USD patch
Clonidine 0.3 mg/day patch 67.28 USD patch
Clonidine hcl powder 53.09 USD g
Clonidine 0.2 mg/day patch 48.5 USD patch
Duraclon 500 mcg/ml vial 47.4 USD ml
Catapres-tts 2 patch 39.23 USD patch
Clonidine 0.1 mg/day patch 28.81 USD patch
Catapres-tts 1 patch 21.18 USD patch
Clonidine 5000 mcg/10 ml vial 21.0 USD ml
Duraclon 0.1 mg/ml vial 14.4 USD ml
Clonidine 1000 mcg/10 ml vial 5.04 USD ml
Catapres 0.3 mg tablet 2.98 USD tablet
Catapres 0.2 mg tablet 2.35 USD tablet
Catapres 0.1 mg tablet 1.57 USD tablet
Clonidine hcl 0.3 mg tablet 0.5 USD tablet
Clonidine hcl 0.2 mg tablet 0.35 USD tablet
Catapres 0.2 mg Tablet 0.35 USD tablet
Apo-Clonidine 0.2 mg Tablet 0.33 USD tablet
Novo-Clonidine 0.2 mg Tablet 0.33 USD tablet
Nu-Clonidine 0.2 mg Tablet 0.33 USD tablet
Dixarit 0.025 mg Tablet 0.28 USD tablet
Clonidine hcl 0.1 mg tablet 0.24 USD tablet
Catapres 0.1 mg Tablet 0.19 USD tablet
Apo-Clonidine 0.1 mg Tablet 0.18 USD tablet
Novo-Clonidine 0.1 mg Tablet 0.18 USD tablet
Nu-Clonidine 0.1 mg Tablet 0.18 USD tablet
Apo-Clonidine 0.025 mg Tablet 0.16 USD tablet
Novo-Clonidine 0.025 mg Tablet 0.16 USD tablet
Patents
Country Patent Number Approved Expires
United States 5869100 1993-10-13 2013-10-13
Properties
State solid
Melting point 130oC
Experimental Properties
Property Value Source
water solubility Appreciable PhysProp
logP 2.7 PhysProp
Caco2 permeability -4.59 [ADME Research, USCD] BiGG
Predicted Properties
Property Value Source
water solubility 4.80e-01 g/l ALOGPS
logP 2.55 ALOGPS
logP 2.49 ChemAxon Molconvert
logS -2.68 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 3 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 36.42 ChemAxon Molconvert
rotatable bond count 1 ChemAxon Molconvert
refractivity 59.09 ChemAxon Molconvert
polarizability 21.70 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Schapiro NA: “Dude, you don’t have Tourette’s:” Tourette’s syndrome, beyond the tics. Pediatr Nurs. 2002 May-Jun;28(3):243-6, 249-53. Pubmed
  2. Hossmann V, Maling TJ, Hamilton CA, Reid JL, Dollery CT: Sedative and cardiovascular effects of clonidine and nitrazepam. Clin Pharmacol Ther. 1980 Aug;28(2):167-76. Pubmed
External Links
Resource Link
KEGG Drug D00281 Link_out
PubChem Compound 2803 Link_out
PubChem Substance 46508119 Link_out
ChemSpider 2701 Link_out
ChEBI 46631 Link_out
ChEMBL 46631 Link_out
Therapeutic Targets Database DAP000231 Link_out
PharmGKB PA449051 Link_out
HET CLU Link_out
Drug Product Database 2247608 Link_out
RxList http://www.rxlist.com/cgi/generic/clonidin.htm Link_out
Drugs.com http://www.drugs.com/clonidine.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/cat1072.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Clonidine Link_out
ATC Codes
  • C02AC01
  • N02CX02
  • S01EA04
  • S01EA03
AHFS Codes
  • 24:08.16
PDB Entries Not Available
FDA label Not Available
MSDS show (73.8 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid alcohol.
  • Take without regard to meals.
Targets

1. Alpha-2A adrenergic receptor

Pharmacological action: yes
Actions: agonist

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

Organism class: human
UniProt ID: P08913 Link_out
Gene: ADRA2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Fairbanks CA, Stone LS, Kitto KF, Nguyen HO, Posthumus IJ, Wilcox GL: alpha(2C)-Adrenergic receptors mediate spinal analgesia and adrenergic-opioid synergy. J Pharmacol Exp Ther. 2002 Jan;300(1):282-90. Pubmed
  2. Hein, L. (2004). α-Adrenergic system. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology (pp. 27-30). Berlin, Germany: Springer.
  3. Lavand’homme PM, Ma W, De Kock M, Eisenach JC: Perineural alpha(2A)-adrenoceptor activation inhibits spinal cord neuroplasticity and tactile allodynia after nerve injury. Anesthesiology. 2002 Oct;97(4):972-80. Pubmed
  4. Ozdogan UK, Lahdesmaki J, Hakala K, Scheinin M: The involvement of alpha 2A-adrenoceptors in morphine analgesia, tolerance and withdrawal in mice. Eur J Pharmacol. 2004 Aug 23;497(2):161-71. Pubmed
  5. Ozdogan UK, Lahdesmaki J, Mansikka H, Scheinin M: Loss of amitriptyline analgesia in alpha 2A-adrenoceptor deficient mice. Eur J Pharmacol. 2004 Feb 6;485(1-3):193-6. Pubmed
  6. Wang XM, Zhang ZJ, Bains R, Mokha SS: Effect of antisense knock-down of alpha(2a)- and alpha(2c)-adrenoceptors on the antinociceptive action of clonidine on trigeminal nociception in the rat. Pain. 2002 Jul;98(1-2):27-35. Pubmed

2. Alpha-2B adrenergic receptor

Pharmacological action: yes
Actions: agonist

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 clonidine > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol

Organism class: human
UniProt ID: P18089 Link_out
Gene: ADRA2B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Hein, L. (2004). α-Adrenergic system. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology (pp. 27-30). Berlin, Germany: Springer.

3. Alpha-2C adrenergic receptor

Pharmacological action: yes
Actions: agonist

Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins

Organism class: human
UniProt ID: P18825 Link_out
Gene: ADRA2C Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Hein, L. (2004). α-Adrenergic system. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology (pp. 27-30). Berlin, Germany: Springer.
Enzymes

1. Cytochrome P450 2D6

Actions: substrate

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

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Claessens AJ, Risler LJ, Eyal S, Shen DD, Easterling TR, Hebert MF: CYP2D6 mediates 4-hydroxylation of clonidine in vitro: implication for pregnancy-induced changes in clonidine clearance. Drug Metab Dispos. 2010 Sep;38(9):1393-6. Epub 2010 Jun 22. Pubmed

2. Cytochrome P450 1A2

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Claessens AJ, Risler LJ, Eyal S, Shen DD, Easterling TR, Hebert MF: CYP2D6 mediates 4-hydroxylation of clonidine in vitro: implication for pregnancy-induced changes in clonidine clearance. Drug Metab Dispos. 2010 Sep;38(9):1393-6. Epub 2010 Jun 22. Pubmed

3. Cytochrome P450 3A4

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Claessens AJ, Risler LJ, Eyal S, Shen DD, Easterling TR, Hebert MF: CYP2D6 mediates 4-hydroxylation of clonidine in vitro: implication for pregnancy-induced changes in clonidine clearance. Drug Metab Dispos. 2010 Sep;38(9):1393-6. Epub 2010 Jun 22. Pubmed

4. Cytochrome P450 1A1

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P04798 Link_out
Gene: CYP1A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Claessens AJ, Risler LJ, Eyal S, Shen DD, Easterling TR, Hebert MF: CYP2D6 mediates 4-hydroxylation of clonidine in vitro: implication for pregnancy-induced changes in clonidine clearance. Drug Metab Dispos. 2010 Sep;38(9):1393-6. Epub 2010 Jun 22. Pubmed

5. Cytochrome P450 3A5

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Claessens AJ, Risler LJ, Eyal S, Shen DD, Easterling TR, Hebert MF: CYP2D6 mediates 4-hydroxylation of clonidine in vitro: implication for pregnancy-induced changes in clonidine clearance. Drug Metab Dispos. 2010 Sep;38(9):1393-6. Epub 2010 Jun 22. Pubmed
Transporters

1. Solute carrier family 22 member 1

Actions: inhibitor

Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)- N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin- dependent kinase II and LCK tyrosine kinase

UniProt ID: O15245 Link_out
Gene: SLC22A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Bednarczyk D, Ekins S, Wikel JH, Wright SH: Influence of molecular structure on substrate binding to the human organic cation transporter, hOCT1. Mol Pharmacol. 2003 Mar;63(3):489-98. Pubmed
  2. Zhang L, Dresser MJ, Gray AT, Yost SC, Terashita S, Giacomini KM: Cloning and functional expression of a human liver organic cation transporter. Mol Pharmacol. 1997 Jun;51(6):913-21. Pubmed
  3. Zhang L, Schaner ME, Giacomini KM: Functional characterization of an organic cation transporter (hOCT1) in a transiently transfected human cell line (HeLa). J Pharmacol Exp Ther. 1998 Jul;286(1):354-61. Pubmed
  4. Martel F, Vetter T, Russ H, Grundemann D, Azevedo I, Koepsell H, Schomig E: Transport of small organic cations in the rat liver. The role of the organic cation transporter OCT1. Naunyn Schmiedebergs Arch Pharmacol. 1996 Aug-Sep;354(3):320-6. Pubmed

2. Solute carrier family 22 member 3

Actions: inhibitor

Mediates potential-dependent transport of a variety of organic cations. May play a significant role in the disposition of cationic neurotoxins and neurotransmitters in the brain

UniProt ID: O75751 Link_out
Gene: SLC22A3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wu X, Huang W, Ganapathy ME, Wang H, Kekuda R, Conway SJ, Leibach FH, Ganapathy V: Structure, function, and regional distribution of the organic cation transporter OCT3 in the kidney. Am J Physiol Renal Physiol. 2000 Sep;279(3):F449-58. Pubmed
  2. Martel F, Grundemann D, Calhau C, Schomig E: Apical uptake of organic cations by human intestinal Caco-2 cells: putative involvement of ASF transporters. Naunyn Schmiedebergs Arch Pharmacol. 2001 Jan;363(1):40-9. Pubmed

3. Organic cation/carnitine transporter 2

Actions: inhibitor

Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Also Relative uptake activity ratio of carnitine to TEA is 11.3

UniProt ID: O76082 Link_out
Gene: SLC22A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Ohashi R, Tamai I, Yabuuchi H, Nezu JI, Oku A, Sai Y, Shimane M, Tsuji A: Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther. 1999 Nov;291(2):778-84. Pubmed
  2. Wu X, Huang W, Prasad PD, Seth P, Rajan DP, Leibach FH, Chen J, Conway SJ, Ganapathy V: Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter. J Pharmacol Exp Ther. 1999 Sep;290(3):1482-92. Pubmed

4. Organic cation/carnitine transporter 1

Actions: inhibitor

Sodium-ion dependent, low affinity carnitine transporter. Probably transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Relative uptake activity ratio of carnitine to TEA is 1.78. A key substrate of this transporter seems to be ergothioneine (ET)

UniProt ID: Q9H015 Link_out
Gene: SLC22A4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Yabuuchi H, Tamai I, Nezu J, Sakamoto K, Oku A, Shimane M, Sai Y, Tsuji A: Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations. J Pharmacol Exp Ther. 1999 May;289(2):768-73. Pubmed

5. Multidrug resistance protein 1

Actions: substrate

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Faassen F, Vogel G, Spanings H, Vromans H: Caco-2 permeability, P-glycoprotein transport ratios and brain penetration of heterocyclic drugs. Int J Pharm. 2003 Sep 16;263(1-2):113-22. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on October 11, 2011 15:27

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.