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Identification
NameEpicept NP-1
Accession NumberDB05492  (DB08290)
TypeSmall Molecule
GroupsInvestigational
Description

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).

Structure
Thumb
SynonymsNot Available
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
CategoriesNot Available
UNIINot Available
CAS numberNot Available
WeightAverage: 209.245
Monoisotopic: 209.116426739
Chemical FormulaC10H15N3O2
InChI KeyInChIKey=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
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassNitrobenzenes
Direct ParentNitrobenzenes
Alternative Parents
Substituents
  • Nitrobenzene
  • Aminotoluene
  • Phenylalkylamine
  • Substituted aniline
  • Toluene
  • Secondary aliphatic/aromatic amine
  • Aniline
  • Organic nitro compound
  • Organic nitrite
  • C-nitro compound
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Allyl-type 1,3-dipolar organic compound
  • Secondary amine
  • Organic oxoazanium
  • Hydrocarbon derivative
  • Organic salt
  • Primary amine
  • Organonitrogen compound
  • Primary aliphatic amine
  • Amine
  • Organic zwitterion
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationInvestigated for use/treatment in neuropathy (diabetic) and pain (acute or chronic).
PharmacodynamicsEpiCept 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 actionThe 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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityMild sensitivity at application site
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9629
Blood Brain Barrier+0.787
Caco-2 permeable-0.5109
P-glycoprotein substrateNon-substrate0.5295
P-glycoprotein inhibitor INon-inhibitor0.7583
P-glycoprotein inhibitor IINon-inhibitor0.8837
Renal organic cation transporterNon-inhibitor0.7637
CYP450 2C9 substrateNon-substrate0.8113
CYP450 2D6 substrateNon-substrate0.7816
CYP450 3A4 substrateNon-substrate0.6621
CYP450 1A2 substrateInhibitor0.8305
CYP450 2C9 inhibitorNon-inhibitor0.5367
CYP450 2D6 inhibitorNon-inhibitor0.8092
CYP450 2C19 inhibitorNon-inhibitor0.547
CYP450 3A4 inhibitorNon-inhibitor0.7969
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7156
Ames testAMES toxic0.8628
CarcinogenicityNon-carcinogens0.5464
BiodegradationNot ready biodegradable0.9626
Rat acute toxicity2.4866 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.5324
hERG inhibition (predictor II)Non-inhibitor0.6512
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.472 mg/mLALOGPS
logP1.8ALOGPS
logP1.81ChemAxon
logS-2.6ALOGPS
pKa (Strongest Acidic)13.99ChemAxon
pKa (Strongest Basic)9.82ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area83.87 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity61.43 m3·mol-1ChemAxon
Polarizability22.54 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. 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. [PubMed:16549702 ]
  2. 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. [PubMed:16202956 ]
  3. 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. [PubMed:15983466 ]
  4. 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. [PubMed:12818961 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
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. Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociati...
Gene Name:
OPRM1
Uniprot ID:
P35372
Molecular Weight:
44778.855 Da
Kind
Protein
Organism
Human
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-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates...
Gene Name:
HTR2A
Uniprot ID:
P28223
Molecular Weight:
52602.58 Da
Kind
Protein
Organism
Human
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 change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins ...
Gene Name:
HTR2B
Uniprot ID:
P41595
Molecular Weight:
54297.41 Da
Kind
Protein
Organism
Human
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-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modul...
Gene Name:
HTR2C
Uniprot ID:
P28335
Molecular Weight:
51820.705 Da
Kind
Protein
Organism
Human
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) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1A
Uniprot ID:
P35348
Molecular Weight:
51486.005 Da
Kind
Protein
Organism
Human
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) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1B
Uniprot ID:
P35368
Molecular Weight:
56835.375 Da
Kind
Protein
Organism
Human
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
Molecular Weight:
60462.205 Da
Kind
Protein
Organism
Human
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 oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianser...
Gene Name:
ADRA2A
Uniprot ID:
P08913
Molecular Weight:
48956.275 Da
Kind
Protein
Organism
Human
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 > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phent...
Gene Name:
ADRA2B
Uniprot ID:
P18089
Molecular Weight:
49565.8 Da
Kind
Protein
Organism
Human
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
Molecular Weight:
49521.585 Da
Kind
Protein
Organism
Human
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 catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.
Gene Name:
HRH1
Uniprot ID:
P35367
Molecular Weight:
55783.61 Da
Kind
Protein
Organism
Human
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-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling via G proteins mediates inhibition of adenylate cyclase activity and calcium channel activity. Arrestins mod...
Gene Name:
OPRL1
Uniprot ID:
P41146
Molecular Weight:
40692.775 Da
Comments
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Drug created on November 18, 2007 11:25 / Updated on August 17, 2016 12:24