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Identification
Name Dexmedetomidine
Accession Number DB00633 (APRD00578)
Type small molecule
Groups approved
Description

An agonist of receptors, adrenergic alpha-2 that is used in veterinary medicine for its analgesic and sedative properties. It is the racemate of dexmedetomidine. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Medetomidina [Spanish]
Medetomidine
Medetomidinum [Latin]
Salts Not Available
Brand names
Name Company
PRECEDEX
Brand mixtures Not Available
Categories
  • Hypnotics and Sedatives
  • Analgesics
  • Adrenergic alpha-Agonists
  • Analgesics, Non-Narcotic
CAS number 113775-47-6
Weight Average: 200.2795
Monoisotopic: 200.131348522
Chemical Formula C13H16N2
InChI Key InChIKey=CUHVIMMYOGQXCV-NSHDSACASA-N
InChI
InChI=1S/C13H16N2/c1-9-5-4-6-12(10(9)2)11(3)13-7-14-8-15-13/h4-8,11H,1-3H3,(H,14,15)/t11-/m0/s1
Plain Text
IUPAC Name
4-[(1S)-1-(2,3-dimethylphenyl)ethyl]-1H-imidazole
SMILES
C[C@H](C1=CNC=N1)C1=C(C)C(C)=CC=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication For sedation of initially intubated and mechanically ventilated patients during treatment in an intensive care setting, also used in pain relief; anxiety reduction and analgesia
Pharmacodynamics Dexmedetomidine activates 2-adrenoceptors, and causes the decrease of sympathetic tone, with attenuation of the neuroendocrine and hemodynamic responses to anesthesia and surgery; it reduces anesthetic and opioid requirements; and causes sedation and analgesia.
Mechanism of action Dexmedetomidine is a specific and selective alpha-2 adrenoceptor agonist. By binding to the presynaptic alpha-2 adrenoceptors, it inhibits the release if norepinephrine, therefore, terminate the propagation of pain signals. Activation of the postsynaptic alpha-2 adrenoceptors inhibits the sympathetic activity decreases blood pressure and heart rate.
Absorption Not Available
Volume of distribution
  • 118 L
Protein binding 94%
Metabolism Hepatic
Route of elimination A mass balance study demonstrated that after nine days an average of 95% of the radioactivity, following intravenous administration of radiolabeled dexmedetomidine, was recovered in the urine and 4% in the feces. Fractionation of the radioactivity excreted in urine demonstrated that products of N-glucuronidation accounted for approximately 34% of the cumulative urinary excretion. The majority of metabolites are excreted in the urine.
Half life 2 hours
Clearance
  • 39 L/h [Healthy volunteers receiving IV infusion (0.2-0.7 mcg/kg/hr)]
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Hospira inc
Packagers
Dosage forms
Form Route Strength
Injection, solution Intravenous
Prices
Unit description Cost Unit
Precedex 200 mcg/2 ml vial 41.32 USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 6716867 1999-03-31 2019-03-31
United States 5344840 1994-09-06 2011-09-06
Canada 2326339 2008-12-23 2019-03-31
Canada 1337659 1995-11-28 2012-11-28
Properties
State solid
Experimental Properties
Property Value Source
water solubility Freely soluble in water Not Available
logP 2.8 Not Available
pKa 7.1 Not Available
Predicted Properties
Property Value Source
water solubility 1.74e-01 g/l ALOGPS
logP 3.28 ALOGPS
logP 3.39 ChemAxon
logS -3.1 ALOGPS
pKa (strongest acidic) 14.09 ChemAxon
pKa (strongest basic) 6.54 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 1 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 28.68 ChemAxon
rotatable bond count 2 ChemAxon
refractivity 62.98 ChemAxon
polarizability 23.32 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00514 Link_out
KEGG Compound C07450 Link_out
ChEBI 4466 Link_out
ChEMBL 4466 Link_out
Therapeutic Targets Database DAP000233 Link_out
PharmGKB PA449256 Link_out
RxList http://www.rxlist.com/cgi/generic/precedex.htm Link_out
Wikipedia http://en.wikipedia.org/wiki/Dexmedetomidine Link_out
ATC Codes
  • N05CM18
AHFS Codes Not Available
PDB Entries Not Available
FDA label show (43.9 KB)
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Tranylcypromine Tranylcypromine, a strong CYP2A6 inhibitor, may decrease the metabolism and clearance of Dexmedetomidine.
Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Trimipramine Trimipramine may reduce the antihypertensive effect of the alpha2-agonist, Dexmedetomidine. Trimipramine may also increase the rebound hypertensive effect of Clonidine. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Clonidine if Trimipramine is initiated, discontinued or dose changed. Dexmedetomidine should be withdrawn very gradually to reduce the risk of hypertensive crisis.
Food Interactions Not Available
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. Scheibner J, Trendelenburg AU, Hein L, Starke K, Blandizzi C: Alpha 2-adrenoceptors in the enteric nervous system: a study in alpha 2A-adrenoceptor-deficient mice. Br J Pharmacol. 2002 Feb;135(3):697-704. Pubmed
  3. Davies MF, Tsui J, Flannery JA, Li X, DeLorey TM, Hoffman BB: Activation of alpha2 adrenergic receptors suppresses fear conditioning: expression of c-Fos and phosphorylated CREB in mouse amygdala. Neuropsychopharmacology. 2004 Feb;29(2):229-39. Pubmed
  4. Dawson C, Ma D, Chow A, Maze M: Dexmedetomidine enhances analgesic action of nitrous oxide: mechanisms of action. Anesthesiology. 2004 Apr;100(4):894-904. Pubmed
  5. 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
  6. Menon DV, Wang Z, Fadel PJ, Arbique D, Leonard D, Li JL, Victor RG, Vongpatanasin W: Central sympatholysis as a novel countermeasure for cocaine-induced sympathetic activation and vasoconstriction in humans. J Am Coll Cardiol. 2007 Aug 14;50(7):626-33. Epub 2007 Jul 30. Pubmed
Enzymes

1. Cytochrome P450 2E1

Actions: substrate

Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms

UniProt ID: P05181 Link_out
Gene: CYP2E1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Avsaroglu H, Bull S, Maas-Bakker RF, Scherpenisse P, Van Lith HA, Bergwerff AA, Hellebrekers LJ, Van Zutphen LF, Fink-Gremmels J: Differences in hepatic cytochrome P450 activity correlate with the strain-specific biotransformation of medetomidine in AX/JU and IIIVO/JU inbred rabbits. J Vet Pharmacol Ther. 2008 Aug;31(4):368-77. Pubmed]
  2. Duhamel MC, Troncy E, Beaudry F: Metabolic stability and determination of cytochrome P450 isoenzymes’ contribution to the metabolism of medetomidine in dog liver microsomes. Biomed Chromatogr. 2010 Aug;24(8):868-77. Pubmed]

2. Cytochrome P450 1A2

Actions: inhibitor

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. Konstandi M, Lang MA, Kostakis D, Johnson EO, Marselos M: Predominant role of peripheral catecholamines in the stress-induced modulation of CYP1A2 inducibility by benzo(alpha)pyrene. Basic Clin Pharmacol Toxicol. 2008 Jan;102(1):35-44. Epub 2007 Oct 31. Pubmed
  2. Konstandi M, Kostakis D, Harkitis P, Johnson EO, Marselos M, Adamidis K, Lang MA: Benzo(alpha)pyrene-induced up-regulation of CYP1A2 gene expression: role of adrenoceptor-linked signaling pathways. Life Sci. 2006 Jun 20;79(4):331-41. Epub 2006 Feb 28. Pubmed]

3. Cytochrome P450 1A1

Actions: inhibitor

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. Konstandi M, Kostakis D, Harkitis P, Marselos M, Johnson EO, Adamidis K, Lang MA: Role of adrenoceptor-linked signaling pathways in the regulation of CYP1A1 gene expression. Biochem Pharmacol. 2005 Jan 15;69(2):277-87. Pubmed

4. Cytochrome P450 2D6

Actions: inhibitor

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. Rodrigues AD, Roberts EM: The in vitro interaction of dexmedetomidine with human liver microsomal cytochrome P4502D6 (CYP2D6). Drug Metab Dispos. 1997 May;25(5):651-5. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19