Identification
- Generic Name
- Epicept NP-1
- DrugBank Accession Number
- DB05492
- Background
EpiCept NP-1 is a prescription topical analgesic cream designed to provide effective, long-term relief from the pain of peripheral neuropathies. Peripheral neuropathies are medical conditions caused by damage to the nerves in the peripheral nervous system. The peripheral nervous system includes nerves that run from the brain and spinal cord to the rest of the body. EpiCept NP-1 Cream is a patented formulation containing two FDA-approved drugs, amitriptyline (a widely-used antidepressant) and ketamine (an NMDA antagonist that is used as an anesthetic).
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Epicept NP-1 (DB05492)
- Weight
- Average: 209.245
Monoisotopic: 209.116426739 - Chemical Formula
- C10H15N3O2
- Synonyms
- Not Available
Pharmacology
- Indication
Investigated for use/treatment in neuropathy (diabetic) and pain (acute or chronic).
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EpiCept NP-1 is a prescription topical analgesic cream designed to provide effective, long-term relief from the pain of peripheral neuropathies. Peripheral neuropathies are medical conditions caused by damage to the nerves in the peripheral nervous system. The peripheral nervous system includes nerves that run from the brain and spinal cord to the rest of the body. It is estimated that these conditions affect more than 15 million people in the U.S. and is associated with conditions that injure peripheral nerves, including herpes zoster, or shingles, diabetes, chemotherapy, HIV and other diseases. Peripheral neuropathies can also be caused by trauma or may result from surgical procedures. EpiCept NP-1 Cream is a patented formulation containing two FDA-approved drugs, amitriptyline (a widely-used antidepressant) and ketamine (an NMDA antagonist that is used as an anesthetic).
- Mechanism of action
The mechanism(s) of action are unclear for Epicept. Both ketamine and amitriptyline inhibit N-methyl-D-aspartate receptors in neuronal preparations and may be involved in sensitization of tetrodotoxin-resistant Na+ currents in nociceptors by blocking Na+ channels. In producing antihyperalgesia with pretreatment, but not posttreatment, regimens, ketamine and amitriptyline resemble the profile of a µ-opioid receptor agonist. In addition to the above effects, amitriptyline also inhibits noradrenaline, 5-HT, and adenosine uptake; inter-acts with opioid mechanisms; blocks Ca2+ channels; and blocks cholinergic, histamine H1, 5-HT2, and {alpha}-adrenergic receptors. Accordingly there are many possible mechanisms at work.
Target Actions Organism UMu-type opioid receptor Not Available Humans U5-hydroxytryptamine receptor 2A Not Available Humans U5-hydroxytryptamine receptor 2B Not Available Humans U5-hydroxytryptamine receptor 2C Not Available Humans UAlpha-1A adrenergic receptor Not Available Humans UAlpha-1B adrenergic receptor Not Available Humans UAlpha-1D adrenergic receptor Not Available Humans UAlpha-2A adrenergic receptor Not Available Humans UAlpha-2B adrenergic receptor Not Available Humans UAlpha-2C adrenergic receptor Not Available Humans UHistamine H1 receptor Not Available Humans UNociceptin receptor Not Available Humans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Mild sensitivity at application site
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Not Available
Categories
- Drug Categories
- Not Available
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as nitrobenzenes. These are compounds containing a nitrobenzene moiety, which consists of a benzene ring with a carbon bearing a nitro group.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Nitrobenzenes
- Direct Parent
- Nitrobenzenes
- Alternative Parents
- Nitrotoluenes / Phenylalkylamines / Nitroaromatic compounds / Aniline and substituted anilines / Aminotoluenes / Secondary alkylarylamines / Propargyl-type 1,3-dipolar organic compounds / Organic oxoazanium compounds / Organopnictogen compounds / Organic zwitterions show 3 more
- Substituents
- Allyl-type 1,3-dipolar organic compound / Amine / Aminotoluene / Aniline or substituted anilines / Aromatic homomonocyclic compound / C-nitro compound / Hydrocarbon derivative / Nitroaromatic compound / Nitrobenzene / Nitrotoluene show 16 more
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- Not Available
- CAS number
- Not Available
- InChI Key
- FKZUPMCBVURANR-UHFFFAOYSA-N
- InChI
- InChI=1S/C10H15N3O2/c1-8-3-4-9(12-6-2-5-11)10(7-8)13(14)15/h3-4,7,12H,2,5-6,11H2,1H3
- IUPAC Name
- N1-(4-methyl-2-nitrophenyl)propane-1,3-diamine
- SMILES
- CC1=CC(=C(NCCCN)C=C1)[N+]([O-])=O
References
- General References
- Sandroni P, Davis MD: Combination gel of 1% amitriptyline and 0.5% ketamine to treat refractory erythromelalgia pain: a new treatment option? Arch Dermatol. 2006 Mar;142(3):283-6. [Article]
- Lynch ME, Clark AJ, Sawynok J, Sullivan MJ: Topical amitriptyline and ketamine in neuropathic pain syndromes: an open-label study. J Pain. 2005 Oct;6(10):644-9. [Article]
- Lynch ME, Clark AJ, Sawynok J, Sullivan MJ: Topical 2% amitriptyline and 1% ketamine in neuropathic pain syndromes: a randomized, double-blind, placebo-controlled trial. Anesthesiology. 2005 Jul;103(1):140-6. [Article]
- Oatway M, Reid A, Sawynok J: Peripheral antihyperalgesic and analgesic actions of ketamine and amitriptyline in a model of mild thermal injury in the rat. Anesth Analg. 2003 Jul;97(1):168-73, table of contents. [Article]
- External Links
- PubChem Compound
- 5276854
- PubChem Substance
- 175427020
- ChemSpider
- 4440796
- BindingDB
- 50398244
- ChEMBL
- CHEMBL609728
- ZINC
- ZINC000028644947
- PDBe Ligand
- NP1
- PDB Entries
- 1wug
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Completed Supportive Care Neurologic toxicity / Pain / Peripheral neuropathy / Unspecified Adult Solid Tumor, Protocol Specific 1 2 Completed Treatment Diabetic Peripheral Neuropathy (DPN) / Neuropathic Pain 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.472 mg/mL ALOGPS logP 1.8 ALOGPS logP 1.81 Chemaxon logS -2.6 ALOGPS pKa (Strongest Acidic) 15.25 Chemaxon pKa (Strongest Basic) 9.82 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 81.19 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 60.43 m3·mol-1 Chemaxon Polarizability 22.52 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9629 Blood Brain Barrier + 0.787 Caco-2 permeable - 0.5109 P-glycoprotein substrate Non-substrate 0.5295 P-glycoprotein inhibitor I Non-inhibitor 0.7583 P-glycoprotein inhibitor II Non-inhibitor 0.8837 Renal organic cation transporter Non-inhibitor 0.7637 CYP450 2C9 substrate Non-substrate 0.8113 CYP450 2D6 substrate Non-substrate 0.7816 CYP450 3A4 substrate Non-substrate 0.6621 CYP450 1A2 substrate Inhibitor 0.8305 CYP450 2C9 inhibitor Non-inhibitor 0.5367 CYP450 2D6 inhibitor Non-inhibitor 0.8092 CYP450 2C19 inhibitor Non-inhibitor 0.547 CYP450 3A4 inhibitor Non-inhibitor 0.7969 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7156 Ames test AMES toxic 0.8628 Carcinogenicity Non-carcinogens 0.5464 Biodegradation Not ready biodegradable 0.9626 Rat acute toxicity 2.4866 LD50, mol/kg Not applicable hERG inhibition (predictor I) Strong inhibitor 0.5324 hERG inhibition (predictor II) Non-inhibitor 0.6512
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
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Virus receptor activity
- Specific Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodop...
- Gene Name
- HTR2A
- Uniprot ID
- P28223
- Uniprot Name
- 5-hydroxytryptamine receptor 2A
- Molecular Weight
- 52602.58 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Serotonin receptor activity
- Specific Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various ergot alkaloid derivatives and psychoactive substances. Ligand binding causes a conformation...
- Gene Name
- HTR2B
- Uniprot ID
- P41595
- Uniprot Name
- 5-hydroxytryptamine receptor 2B
- Molecular Weight
- 54297.41 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Serotonin receptor activity
- Specific Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-...
- Gene Name
- HTR2C
- Uniprot ID
- P28335
- Uniprot Name
- 5-hydroxytryptamine receptor 2C
- Molecular Weight
- 51820.705 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Protein heterodimerization activity
- Specific Function
- This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
- Gene Name
- ADRA1A
- Uniprot ID
- P35348
- Uniprot Name
- Alpha-1A adrenergic receptor
- Molecular Weight
- 51486.005 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Protein heterodimerization activity
- Specific Function
- This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
- Gene Name
- ADRA1B
- Uniprot ID
- P35368
- Uniprot Name
- Alpha-1B adrenergic receptor
- Molecular Weight
- 56835.375 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Alpha1-adrenergic receptor activity
- Specific Function
- This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
- Gene Name
- ADRA1D
- Uniprot ID
- P25100
- Uniprot Name
- Alpha-1D adrenergic receptor
- Molecular Weight
- 60462.205 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Thioesterase binding
- Specific Function
- 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 oxymetazo...
- Gene Name
- ADRA2A
- Uniprot ID
- P08913
- Uniprot Name
- Alpha-2A adrenergic receptor
- Molecular Weight
- 48956.275 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Epinephrine binding
- Specific Function
- 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 clonidine...
- Gene Name
- ADRA2B
- Uniprot ID
- P18089
- Uniprot Name
- Alpha-2B adrenergic receptor
- Molecular Weight
- 49565.8 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Protein homodimerization activity
- Specific Function
- Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
- Gene Name
- ADRA2C
- Uniprot ID
- P18825
- Uniprot Name
- Alpha-2C adrenergic receptor
- Molecular Weight
- 49521.585 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Histamine receptor activity
- Specific Function
- In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
- Gene Name
- HRH1
- Uniprot ID
- P35367
- Uniprot Name
- Histamine H1 receptor
- Molecular Weight
- 55783.61 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Nociceptin receptor activity
- Specific Function
- G-protein coupled opioid receptor that functions as receptor for the endogenous neuropeptide nociceptin. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-b...
- Gene Name
- OPRL1
- Uniprot ID
- P41146
- Uniprot Name
- Nociceptin receptor
- Molecular Weight
- 40692.775 Da
Drug created at November 18, 2007 18:25 / Updated at June 12, 2020 16:52