Levallorphan
Identification
- Name
- Levallorphan
- Accession Number
- DB00504 (APRD00733)
- Type
- Small Molecule
- Groups
- Approved
- Description
An opioid antagonist with properties similar to those of naloxone; in addition it also possesses some agonist properties. It should be used cautiously; levallorphan reverses severe opioid-induced respiratory depression but may exacerbate respiratory depression such as that induced by alcohol or other non-opioid central depressants. (From Martindale, The Extra Pharmacopoeia, 30th ed, p683)
- Structure
- Synonyms
- Levallofano
- Levallorphan
- Lévallorphane
- Levallorphanum
- Levalorfano
- External IDs
- HSDB 2148 / Ro-1-7700
- Product Ingredients
Ingredient UNII CAS InChI Key Levallorphan tartrate U0VSF7HTN0 71-82-9 FWMLYVACGDQRFU-ZTMWJVNESA-N - International/Other Brands
- Lorfan (Takeda)
- Categories
- UNII
- 353613BU4U
- CAS number
- 152-02-3
- Weight
- Average: 283.4079
Monoisotopic: 283.193614427 - Chemical Formula
- C19H25NO
- InChI Key
- OZYUPQUCAUTOBP-QXAKKESOSA-N
- InChI
- InChI=1S/C19H25NO/c1-2-10-20-11-9-19-8-4-3-5-16(19)18(20)12-14-6-7-15(21)13-17(14)19/h2,6-7,13,16,18,21H,1,3-5,8-12H2/t16-,18+,19+/m0/s1
- IUPAC Name
- (1R,9R,10R)-17-(prop-2-en-1-yl)-17-azatetracyclo[7.5.3.0¹,¹⁰.0²,⁷]heptadeca-2(7),3,5-trien-4-ol
- SMILES
- [H][C@@]12CCCC[C@@]11CCN(CC=C)[C@@H]2CC2=C1C=C(O)C=C2
Pharmacology
- Indication
For the complete or partial reversal of narcotic depression, including respiratory depression, induced by opioids.
- Pharmacodynamics
Levallorphan, an opioid antagonist similar to naloxone, is used to treat drug overdoses. Levallorphan differs from naloxone in that it also possesses some agonist properties. It is an analogue of levelorphanol that counteracts the actions of narcotic analgesics such as morphine. It is used especially in the treatment of respiratory depression due to narcotic overdoses. Levallorphan prevents or reverses the effects of opioids including respiratory depression, sedation and hypotension. Also, it can reverse the psychotomimetic and dysphoric effects of agonist-antagonists such as pentazocine.
- Mechanism of action
Levallorphan antagonizes opioid effects by competing for the same receptor sites. It binds to the opioid mu receptor and the nicotinic acetylcholine receptor alpha2/alpha3.
Target Actions Organism AMu-type opioid receptor partial agonistHumans - Absorption
Rapidly absorbed.
- Volume of distribution
- Not Available
- Protein binding
- Not Available
- Metabolism
Hepatic.
- Route of elimination
- Not Available
- Half life
1 hour
- Clearance
- Not Available
- Toxicity
Oral, rat LD50: 109±4 mg/kg
- Affected organisms
- Humans and other mammals
- Pathways
Pathway Category Levallorphan Action Pathway Drug action - Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
Drug Interaction Alfentanil The therapeutic efficacy of Alfentanil can be decreased when used in combination with Levallorphan. Alphacetylmethadol The therapeutic efficacy of Alphacetylmethadol can be decreased when used in combination with Levallorphan. Alphaprodine The therapeutic efficacy of Alphaprodine can be decreased when used in combination with Levallorphan. Bezitramide The therapeutic efficacy of Bezitramide can be decreased when used in combination with Levallorphan. Buprenorphine The therapeutic efficacy of Buprenorphine can be decreased when used in combination with Levallorphan. Butorphanol The therapeutic efficacy of Butorphanol can be decreased when used in combination with Levallorphan. Carfentanil The therapeutic efficacy of Carfentanil can be decreased when used in combination with Levallorphan. Codeine The therapeutic efficacy of Codeine can be decreased when used in combination with Levallorphan. Dextromoramide The therapeutic efficacy of Dextromoramide can be decreased when used in combination with Levallorphan. Dextropropoxyphene The therapeutic efficacy of Dextropropoxyphene can be decreased when used in combination with Levallorphan. - Food Interactions
- Not Available
References
- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0014647
- KEGG Compound
- C07069
- PubChem Compound
- 5359371
- PubChem Substance
- 46505682
- ChemSpider
- 10481920
- BindingDB
- 50326673
- ChEBI
- 6431
- ChEMBL
- CHEMBL1254682
- Therapeutic Targets Database
- DAP000348
- PharmGKB
- PA164749284
- Wikipedia
- Levallorphan
Clinical Trials
Pharmacoeconomics
- Manufacturers
- Hoffmann la roche inc
- Packagers
- Not Available
- Dosage forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 181 °C PhysProp water solubility 633 mg/L Not Available logP 3.48 HANSCH,C ET AL. (1995) - Predicted Properties
Property Value Source Water Solubility 0.0252 mg/mL ALOGPS logP 3.91 ALOGPS logP 3.76 ChemAxon logS -4 ALOGPS pKa (Strongest Acidic) 10.36 ChemAxon pKa (Strongest Basic) 9.41 ChemAxon Physiological Charge 1 ChemAxon Hydrogen Acceptor Count 2 ChemAxon Hydrogen Donor Count 1 ChemAxon Polar Surface Area 23.47 Å2 ChemAxon Rotatable Bond Count 2 ChemAxon Refractivity 87.24 m3·mol-1 ChemAxon Polarizability 32.68 Å3 ChemAxon Number of Rings 4 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule Yes ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET features
Property Value Probability Human Intestinal Absorption + 0.9691 Blood Brain Barrier + 0.9948 Caco-2 permeable + 0.7313 P-glycoprotein substrate Substrate 0.7698 P-glycoprotein inhibitor I Inhibitor 0.6659 P-glycoprotein inhibitor II Inhibitor 0.6439 Renal organic cation transporter Inhibitor 0.7978 CYP450 2C9 substrate Non-substrate 0.8101 CYP450 2D6 substrate Substrate 0.5731 CYP450 3A4 substrate Substrate 0.5438 CYP450 1A2 substrate Non-inhibitor 0.5676 CYP450 2C9 inhibitor Non-inhibitor 0.8877 CYP450 2D6 inhibitor Inhibitor 0.8931 CYP450 2C19 inhibitor Non-inhibitor 0.8743 CYP450 3A4 inhibitor Non-inhibitor 0.8409 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5908 Ames test Non AMES toxic 0.7723 Carcinogenicity Non-carcinogens 0.9563 Biodegradation Not ready biodegradable 0.9973 Rat acute toxicity 2.5065 LD50, mol/kg Not applicable hERG inhibition (predictor I) Strong inhibitor 0.6508 hERG inhibition (predictor II) Non-inhibitor 0.5385
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Taxonomy
- Description
- This compound belongs to the class of organic compounds known as morphinans. These are polycyclic compounds with a four-ring skeleton with three condensed six-member rings forming a partially hydrogenated phenanthrene moiety, one of which is aromatic while the two others are alicyclic.
- Kingdom
- Organic compounds
- Super Class
- Alkaloids and derivatives
- Class
- Morphinans
- Sub Class
- Not Available
- Direct Parent
- Morphinans
- Alternative Parents
- Phenanthrenes and derivatives / Benzazocines / Tetralins / Aralkylamines / 1-hydroxy-2-unsubstituted benzenoids / Piperidines / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds show 1 more
- Substituents
- Morphinan / Phenanthrene / Benzazocine / Tetralin / 1-hydroxy-2-unsubstituted benzenoid / Aralkylamine / Piperidine / Benzenoid / Tertiary aliphatic amine / Tertiary amine show 10 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- morphinane alkaloid (CHEBI:6431)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Partial 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
- Picker MJ, Benyas S, Horwitz JA, Thompson K, Mathewson C, Smith MA: Discriminative stimulus effects of butorphanol: influence of training dose on the substitution patterns produced by Mu, Kappa and Delta opioid agonists. J Pharmacol Exp Ther. 1996 Dec;279(3):1130-41. [PubMed:8968334]
- Traynor JR, Nahorski SR: Modulation by mu-opioid agonists of guanosine-5'-O-(3-[35S]thio)triphosphate binding to membranes from human neuroblastoma SH-SY5Y cells. Mol Pharmacol. 1995 Apr;47(4):848-54. [PubMed:7723747]
- Selley DE, Sim LJ, Xiao R, Liu Q, Childers SR: mu-Opioid receptor-stimulated guanosine-5'-O-(gamma-thio)-triphosphate binding in rat thalamus and cultured cell lines: signal transduction mechanisms underlying agonist efficacy. Mol Pharmacol. 1997 Jan;51(1):87-96. [PubMed:9016350]
- Emmerson PJ, Clark MJ, Mansour A, Akil H, Woods JH, Medzihradsky F: Characterization of opioid agonist efficacy in a C6 glioma cell line expressing the mu opioid receptor. J Pharmacol Exp Ther. 1996 Sep;278(3):1121-7. [PubMed:8819494]
- Morgan D, Picker MJ: The mu opioid irreversible antagonist beta-funaltrexamine differentiates the discriminative stimulus effects of opioids with high and low efficacy at the mu opioid receptor. Psychopharmacology (Berl). 1998 Nov;140(1):20-8. [PubMed:9862398]
Drug created on June 13, 2005 07:24 / Updated on January 01, 2019 11:03