Identification

Name
Dezocine
Accession Number
DB01209  (APRD00912)
Type
Small Molecule
Groups
Approved, Investigational
Description

Dezocine is a partial opiate drug and is used for pain management. Dezocine is a very effective alternative to fentanyl when administered during outpatient laparoscopy, although is associated with an increased incidence of postoperative nausea.

Structure
Thumb
Synonyms
  • (-)-13beta-amino-5,6,7,8,9,10,11alpha,12-Octahydro-5alpha-methyl-5,11-methanobenzocyclodecen-3-ol
  • Dezocina
  • Dezocinum
External IDs
WY-16,225 / WY-16225
International/Other Brands
Dalgan
Categories
UNII
VHX8K5SV4X
CAS number
53648-55-8
Weight
Average: 245.3599
Monoisotopic: 245.177964363
Chemical Formula
C16H23NO
InChI Key
VTMVHDZWSFQSQP-VBNZEHGJSA-N
InChI
InChI=1S/C16H23NO/c1-16-8-4-2-3-5-12(15(16)17)9-11-6-7-13(18)10-14(11)16/h6-7,10,12,15,18H,2-5,8-9,17H2,1H3/t12-,15-,16+/m0/s1
IUPAC Name
(1R,9S,15S)-15-amino-1-methyltricyclo[7.5.1.0²,⁷]pentadeca-2,4,6-trien-4-ol
SMILES
[H][C@@]12CC3=CC=C(O)C=C3[C@@](C)(CCCCC1)[C@H]2N

Pharmacology

Indication

Indicated in the treatment of moderate to severe pain.

Pharmacodynamics

Dezocine is a parenteral narcotic analgesic possessing both agonist and antagonist activity. It is similar to morphine with respect to analgesic potency and onset and duration of action. The narcotic antagonist activity is greater than that of pentazocine.

Mechanism of action

Dezocine is a opioid analgesic drug of mixed agonist-antagonist type. It binds with stereospecific receptors at many sites within the central nervous system (CNS) to alter processes affecting both the perception of pain and the emotional response to pain. At least 2 of these types of receptors (mu and kappa) mediate analgesia. Mu receptors are widely distributed throughout the CNS, especially in the limbic system (frontal cortex, temporal cortex, amygdala, and hippocampus), thalamus, striatum, hypothalamus, and midbrain as well as laminae I, II, IV, and V of the dorsal horn in the spinal cord. Kappa receptors are localized primarily in the spinal cord and in the cerebral cortex.

TargetActionsOrganism
AMu-type opioid receptor
agonist
Human
AKappa-type opioid receptor
antagonist
Human
Absorption

Rapid and complete following intramuscular administration.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hepatic, via conjugation (glucuronidation).

Route of elimination
Not Available
Half life

Elimination half-life following intramuscular administration averages 2.2 hours. Elimination half-life following a 5mg intravenous dose averages 1.7 to 2.6 hours (range 0.6 to 4.4 hours) while a 10mg dose averages 2.4 to 2.6 hours (range 1.2 to 7.4 hours). In patients with hepatic cirrhosis, the half-life is increased by 30 to 50%.

Clearance
Not Available
Toxicity

Symptoms of overdose include cold and clammy skin, confusion, nervousness, or severe restlessness, convulsions (seizures), severe dizziness, severe drowsiness, low blood pressure, pinpoint pupils of eyes, slow heartbeat, slow or troubled breathing and severe weakness.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Dezocine Action PathwayDrug action
Dezocine Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may increase the analgesic activities of Dezocine.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may increase the analgesic activities of Dezocine.
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may increase the analgesic activities of Dezocine.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may increase the analgesic activities of Dezocine.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when Dezocine is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
AceprometazineThe risk or severity of adverse effects can be increased when Dezocine is combined with Aceprometazine.
AcetazolamideThe risk or severity of adverse effects can be increased when Dezocine is combined with Acetazolamide.
AclidiniumThe risk or severity of adverse effects can be increased when Aclidinium is combined with Dezocine.
AdipiplonThe risk or severity of adverse effects can be increased when Dezocine is combined with Adipiplon.
AgmatineThe risk or severity of adverse effects can be increased when Agmatine is combined with Dezocine.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015340
KEGG Drug
D00838
KEGG Compound
C08010
PubChem Compound
3033053
PubChem Substance
46508770
ChemSpider
2297867
BindingDB
50276568
ChEBI
4474
ChEMBL
CHEMBL1685
Therapeutic Targets Database
DAP001100
PharmGKB
PA164746059
Wikipedia
Dezocine
ATC Codes
N02AX03 — Dezocine

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedPreventionCatheter Related Bladder Discomfort1
4RecruitingHealth Services ResearchAnalgesia, Patient-Controlled1
4RecruitingPreventionAwake Tracheal Intubation1
Not AvailableCompletedPreventionAdverse Effects1
Not AvailableUnknown StatusTreatmentBronchoscopy; / Central Airway Stenosis / Interventional; / Noninvasive Positive Pressure Ventilation / Sedation therapy1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP3.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.014 mg/mLALOGPS
logP3.77ALOGPS
logP3.23ChemAxon
logS-4.2ALOGPS
pKa (Strongest Acidic)10.43ChemAxon
pKa (Strongest Basic)9.67ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area46.25 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity74.19 m3·mol-1ChemAxon
Polarizability28.49 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9932
Blood Brain Barrier+0.9403
Caco-2 permeable+0.6275
P-glycoprotein substrateSubstrate0.6181
P-glycoprotein inhibitor INon-inhibitor0.9556
P-glycoprotein inhibitor IINon-inhibitor0.8905
Renal organic cation transporterNon-inhibitor0.7672
CYP450 2C9 substrateNon-substrate0.7337
CYP450 2D6 substrateNon-substrate0.6473
CYP450 3A4 substrateSubstrate0.5845
CYP450 1A2 substrateInhibitor0.5521
CYP450 2C9 inhibitorNon-inhibitor0.7985
CYP450 2D6 inhibitorNon-inhibitor0.8933
CYP450 2C19 inhibitorNon-inhibitor0.7939
CYP450 3A4 inhibitorNon-inhibitor0.7701
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5
Ames testNon AMES toxic0.7561
CarcinogenicityNon-carcinogens0.8934
BiodegradationNot ready biodegradable0.9865
Rat acute toxicity2.4549 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8997
hERG inhibition (predictor II)Inhibitor0.6053
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as tetralins. These are polycyclic aromatic compounds containing a tetralin moiety, which consists of a benzene fused to a cyclohexane.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Tetralins
Sub Class
Not Available
Direct Parent
Tetralins
Alternative Parents
Aralkylamines / 1-hydroxy-2-unsubstituted benzenoids / Organopnictogen compounds / Organooxygen compounds / Monoalkylamines / Hydrocarbon derivatives
Substituents
Tetralin / 1-hydroxy-2-unsubstituted benzenoid / Aralkylamine / Organic nitrogen compound / Organic oxygen compound / Organopnictogen compound / Hydrocarbon derivative / Primary amine / Organooxygen compound / Organonitrogen compound
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
phenols, primary amino compound (CHEBI:4474)

Targets

Details
1. Mu-type opioid receptor
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Voltage-gated calcium channel activity
Specific Function
Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone...
Gene Name
OPRM1
Uniprot ID
P35372
Uniprot Name
Mu-type opioid receptor
Molecular Weight
44778.855 Da
References
  1. Picker MJ: Discriminative stimulus effects of the mixed-opioid agonist/antagonist dezocine: cross-substitution by mu and delta opioid agonists. J Pharmacol Exp Ther. 1997 Dec;283(3):1009-17. [PubMed:9399970]
  2. Barrett AC, Cook CD, Terner JM, Craft RM, Picker MJ: Importance of sex and relative efficacy at the mu opioid receptor in the development of tolerance and cross-tolerance to the antinociceptive effects of opioids. Psychopharmacology (Berl). 2001 Nov;158(2):154-64. [PubMed:11702089]
  3. Cook CD, Barrett AC, Roach EL, Bowman JR, Picker MJ: Sex-related differences in the antinociceptive effects of opioids: importance of rat genotype, nociceptive stimulus intensity, and efficacy at the mu opioid receptor. Psychopharmacology (Berl). 2000 Jul;150(4):430-42. [PubMed:10958085]
  4. Gharagozlou P, Demirci H, David Clark J, Lameh J: Activity of opioid ligands in cells expressing cloned mu opioid receptors. BMC Pharmacol. 2003 Jan 4;3:1. Epub 2003 Jan 4. [PubMed:12513698]
  5. Morgan D, Cook CD, Smith MA, Picker MJ: An examination of the interactions between the antinociceptive effects of morphine and various mu-opioids: the role of intrinsic efficacy and stimulus intensity. Anesth Analg. 1999 Feb;88(2):407-13. [PubMed:9972766]
  6. Jacobs AM, Youngblood F: Opioid receptor affinity for agonist-antagonist analgesics. J Am Podiatr Med Assoc. 1992 Oct;82(10):520-4. [PubMed:1361946]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Opioid receptor activity
Specific Function
G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synt...
Gene Name
OPRK1
Uniprot ID
P41145
Uniprot Name
Kappa-type opioid receptor
Molecular Weight
42644.665 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Gharagozlou P, Hashemi E, DeLorey TM, Clark JD, Lameh J: Pharmacological profiles of opioid ligands at kappa opioid receptors. BMC Pharmacol. 2006 Jan 25;6:3. [PubMed:16433932]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on June 13, 2005 07:24 / Updated on August 02, 2018 04:33