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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
(+)-4-((S)-alpha,2,3-Trimethylbenzyl)imidazoleNot AvailableNot Available
(+)-medetomidineNot AvailableIS
(S)-medetomidineNot AvailableIS
DexmedetomidinGermanINN
DexmedetomidinaSpanishINN
DexmédétomidineFrenchINN
DexmedetomidinumLatinINN
MPV 1440Not AvailableNot Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Precedexinjection, solution, concentrate100 ug/mLintravenousHospira, Inc.1999-12-17Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Precedexinjection, solution4 ug/mLintravenousHospira, Inc.2013-03-13Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Dexmedetomidine Hydrochlorideinjection, solution, concentrate100 ug/mLintravenousSandoz Inc.2014-10-03Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Precedexsolution100 µgintravenousHospira Healthcare CorporationNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Dexmedetomidineinjection, solution, concentrate100 ug/mLintravenousAkorn, Inc.2014-11-24Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Dexmedetomidine Hydrochlorideinjection, solution, concentrate100 ug/mLintravenousPar Pharmaceutical, Inc.2014-08-19Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Dexmedetomidine Hydrochlorideinjection, solution, concentrate100 ug/mLintravenousMylan Institutional LLC2014-08-18Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Over the Counter ProductsNot Available
International Brands
NameCompany
DexdorOrion
DexemThemis Medicare
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Dexmedetomidine Hydrochloride
ThumbNot applicableDBSALT001013
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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as benzene and substituted derivatives. These are aromatic compounds containing one monocyclic ring system consisting of benzene.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassNot Available
Direct ParentBenzene and substituted derivatives
Alternative Parents
Substituents
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Imidazole
  • Azole
  • Azacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
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
PropertyValueProbability
Human Intestinal Absorption+0.9928
Blood Brain Barrier+0.9663
Caco-2 permeable+0.5471
P-glycoprotein substrateNon-substrate0.7118
P-glycoprotein inhibitor INon-inhibitor0.8925
P-glycoprotein inhibitor IINon-inhibitor0.9845
Renal organic cation transporterNon-inhibitor0.824
CYP450 2C9 substrateNon-substrate0.8067
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.7558
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 substrateInhibitor0.5083
CYP450 2D6 substrateNon-inhibitor0.8218
CYP450 2C19 substrateInhibitor0.8564
CYP450 3A4 substrateInhibitor0.5684
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6714
Ames testNon AMES toxic0.6167
CarcinogenicityNon-carcinogens0.9178
BiodegradationNot ready biodegradable0.948
Rat acute toxicity2.4712 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9581
hERG inhibition (predictor II)Non-inhibitor0.9236
Pharmacoeconomics
Manufacturers
  • Hospira inc
Packagers
Dosage forms
FormRouteStrength
Injection, solutionintravenous4 ug/mL
Injection, solution, concentrateintravenous100 ug/mL
Solutionintravenous100 µg
Prices
Unit descriptionCostUnit
Precedex 200 mcg/2 ml vial41.32USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
Canada13376591995-11-282012-11-28
Canada23263392008-12-232019-03-31
United States53448401994-09-062011-09-06
United States67168671999-03-312019-03-31
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubilityFreely soluble in waterNot Available
logP2.8Not Available
pKa7.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.174 mg/mLALOGPS
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 Area28.68 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity62.98 m3·mol-1ChemAxon
Polarizability23.32 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
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
ATC CodesN05CM18
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (43.9 KB)
MSDSNot Available
Interactions
Drug InteractionsNot Available
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