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Identification
NameDexmedetomidine
Accession NumberDB00633  (APRD00578)
Typesmall molecule
Groupsapproved
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
Synonyms
SynonymLanguageCode
(+)-medetomidineNot AvailableIS
(S)-medetomidineNot AvailableIS
DexmedetomidinGermanINN
DexmedetomidinaSpanishINN
DexmédétomidineFrenchINN
DexmedetomidinumLatinINN
Salts
Name/CAS Structure Properties
Dexmedetomidine Hydrochloride
Thumb Not applicable DBSALT001013
Brand names
NameCompany
DexdorOrion
DexemThemis Medicare
PrecedexAbbott
Brand mixturesNot Available
Categories
CAS number113775-47-6
WeightAverage: 200.2795
Monoisotopic: 200.131348522
Chemical FormulaC13H16N2
InChI KeyCUHVIMMYOGQXCV-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
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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassToluenes
Direct parentToluenes
Alternative parentsImidazoles; Polyamines
Substituentsimidazole; azole; polyamine; organonitrogen compound
Classification descriptionThis compound belongs to the toluenes. These are compounds containing a benzene ring which bears a methane group.
Pharmacology
IndicationFor sedation of initially intubated and mechanically ventilated patients during treatment in an intensive care setting, also used in pain relief; anxiety reduction and analgesia
PharmacodynamicsDexmedetomidine 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 actionDexmedetomidine 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.
AbsorptionNot Available
Volume of distribution
  • 118 L
Protein binding94%
Metabolism

Hepatic

Route of eliminationA 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 life2 hours
Clearance
  • 39 L/h [Healthy volunteers receiving IV infusion (0.2-0.7 mcg/kg/hr)]
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9928
Blood Brain Barrier + 0.9663
Caco-2 permeable + 0.5471
P-glycoprotein substrate Non-substrate 0.7118
P-glycoprotein inhibitor I Non-inhibitor 0.8925
P-glycoprotein inhibitor II Non-inhibitor 0.9845
Renal organic cation transporter Non-inhibitor 0.824
CYP450 2C9 substrate Non-substrate 0.8067
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Non-substrate 0.7558
CYP450 1A2 substrate Inhibitor 0.9107
CYP450 2C9 substrate Inhibitor 0.5083
CYP450 2D6 substrate Non-inhibitor 0.8218
CYP450 2C19 substrate Inhibitor 0.8564
CYP450 3A4 substrate Inhibitor 0.5684
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.6714
Ames test Non AMES toxic 0.6167
Carcinogenicity Non-carcinogens 0.9178
Biodegradation Not ready biodegradable 0.948
Rat acute toxicity 2.4712 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9581
hERG inhibition (predictor II) Non-inhibitor 0.9236
Pharmacoeconomics
Manufacturers
  • Hospira inc
Packagers
Dosage forms
FormRouteStrength
Injection, solutionIntravenous
Prices
Unit descriptionCostUnit
Precedex 200 mcg/2 ml vial41.32USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States67168671999-03-312019-03-31
United States53448401994-09-062011-09-06
Canada23263392008-12-232019-03-31
Canada13376591995-11-282012-11-28
Properties
Statesolid
Experimental Properties
PropertyValueSource
water solubilityFreely soluble in waterNot Available
logP2.8Not Available
pKa7.1Not Available
Predicted Properties
PropertyValueSource
water solubility1.74e-01 g/lALOGPS
logP3.28ALOGPS
logP3.39ChemAxon
logS-3.1ALOGPS
pKa (strongest acidic)14.09ChemAxon
pKa (strongest basic)6.54ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count1ChemAxon
hydrogen donor count1ChemAxon
polar surface area28.68ChemAxon
rotatable bond count2ChemAxon
refractivity62.98ChemAxon
polarizability23.32ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Inese Reine, Armands Zandersons, “METHOD FOR PREPARING MEDETOMIDINE AND ITS SALTS..” U.S. Patent US20100048915, issued February 25, 2010.

US20100048915
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00514
KEGG CompoundC07450
ChEBI4466
ChEMBLCHEMBL778
Therapeutic Targets DatabaseDAP000233
PharmGKBPA449256
RxListhttp://www.rxlist.com/cgi/generic/precedex.htm
WikipediaDexmedetomidine
ATC CodesN05CM18
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelshow(43.9 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
TranylcypromineTranylcypromine, a strong CYP2A6 inhibitor, may decrease the metabolism and clearance of Dexmedetomidine.
TreprostinilAdditive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
TrimipramineTrimipramine 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 InteractionsNot Available

Targets

1. Alpha-2A adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Alpha-2A adrenergic receptor P08913 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2E1 P05181 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 1A1 P04798 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

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

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11