Identification

Name
Zucapsaicin
Accession Number
DB09120
Type
Small Molecule
Groups
Approved
Description

Zucapsaicin, the cis-isomer of capsaicin, is a topical analgesic used to treat osteoarthritis of the knee and other neuropathic pain. It is a modulator of transient receptor potential cation channel subfamily V member 1 (TRPV-1), also known as the vanilloid or capsaicin receptor 1, that reduces pain and improves articular functions. Zucapsaicin has also been tested for treatment of a variety of conditions associated with ongoing nerve pain. This includes herpes simplex infections; cluster headaches and migraine; and knee osteoarthritis. It was approved by the Health Canada in 2010 as topical cream marketed under the brand name Zuacta but currently not FDA-approved.

Structure
Thumb
Synonyms
  • (Z)-Capsaicin
  • cis-Capsaicin
  • Civamide
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ZuactaCream0.075 %TopicalSanofi Aventis2011-08-24Not applicableCanada
International/Other Brands
Civanex
Categories
UNII
15OX67P384
CAS number
25775-90-0
Weight
Average: 305.4119
Monoisotopic: 305.199093735
Chemical Formula
C18H27NO3
InChI Key
YKPUWZUDDOIDPM-VURMDHGXSA-N
InChI
InChI=1S/C18H27NO3/c1-14(2)8-6-4-5-7-9-18(21)19-13-15-10-11-16(20)17(12-15)22-3/h6,8,10-12,14,20H,4-5,7,9,13H2,1-3H3,(H,19,21)/b8-6-
IUPAC Name
(6Z)-N-[(4-hydroxy-3-methoxyphenyl)methyl]-8-methylnon-6-enamide
SMILES
COC1=C(O)C=CC(CNC(=O)CCCC\C=C/C(C)C)=C1

Pharmacology

Indication

Indicated to be used in conjunction with oral COX-2 inhibitors or NSAIDs for the relief of severe pain in adult patients with osteoarthritis of the knee, not controlled with oral COX-2 inhibitors or NSAIDs alone, for a duration of no more than three months.

Structured Indications
Pharmacodynamics

Zucapsaicin mediates an antinociceptive action via acting as an agonist at TRPV1. TRPV1 play an important physiological role of transducing chemical, mechanical and thermal stimuli as well as pain transduction, and participate in pain modulation and perception. They are mainly distributed in C sensory nerve fibers as well as Aẟ fibers to transmit sensory information involving inflammatory and neuropathic pain, and activation of these channels releasesomatostatin, calcitonin gene-related peptide (CGRP) and other neuropeptides (neurokinin A, kassinin), leading to neurogenic inflammation [1]. Zucapsaicin is also reported to affect the peptidergic afferent neurons via a desensitization mechanism to decrease the levels of dorsal root ganglia and sciatic calcitonin gene-related peptide (CGRP) and substance P (SP) [5].

Mechanism of action

Zucapsaicin excites and desensitizes C-fibers via agonist at TRPV1 on nociceptive neurons. It binds to intracellular sites and initially stimulates the channels, causing burning sensation. Activation of TRPV1 results in calcium influx and sodium, which leads to cell depolarization. Hypersensitization by zucapsaicin is then followed by reduced sensitivity and persistent desensitization (tachyphylaxis) of the channels via various pathways. Densentiziation is thought to be dependent on intraceullar levels of calcium [4]. Decreased TRPV1 channel action and release of inflammatory neuropeptides induces an analgesic effect, and pain relief [1, 2]. Zucapsaicin activates calcineurin and calcium-dependent protein kinase C isoforms which results in phosphorylation of TRPV1. Phosphorylation of TRPV1 enhances reponsivity to zucapsaicin by potentiating capsaicin- or proton-evoked responses and reducing the temperature threshold for TRPV1 activation [4]. Studies suggest that zucapsaicin is involved in activation of phospholipase C with the subsequent phosphatidylinositol 4,5-biphosphate (PIP2) hydrolysis, which results in TRPV1 inactivation [4]. Tachyphylaxis or persistent desensitization is reversible, and involves the downregulation of proalgesic substances (such as SP) and upregulation of analgesic peptides [1].

TargetActionsOrganism
ATransient receptor potential cation channel subfamily V member 1
agonist
activator
Human
Absorption

Zucapsaicin displays low systemic absorption and localizes at the area of application. In animal studies, systemic absorption is 0.075% [5].

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

In vitro studies demonstrates weak to moderate inhibitiory effects on various cytochrome P450 enzymes, although not clinically significant due to low systemic absorption.

Route of elimination

In rat studies, zucapsaicin and its metabolites are slowly excreted into urine and feces (up to 2/3), with minimal elimination via exhalation following dermal administration [5].

Half life

In rats, the elimination half life of zucapsaicin and its metabolites is approximately 7 to 11 hours [5].

Clearance
Not Available
Toxicity

Most common adverse effects involved application site reactions such as transient burning and warm sensation. Other adverse effects observed in clinical trials are eye irritation, arthralgia, aggravated osteoarthritis, burning sensation, headache, cough and sneezing. Oral LD50 in mouse is >87.5 mg/kg in male and <60 mg/kg in females. Oral LD50 in rats is >90 mg/kg in males and >60 mg/kg in females [5].

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Zucapsaicin.Approved
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Zucapsaicin.Approved
AdinazolamThe metabolism of Adinazolam can be decreased when combined with Zucapsaicin.Approved
AgomelatineThe serum concentration of Agomelatine can be increased when it is combined with Zucapsaicin.Approved, Investigational
AlbendazoleThe metabolism of Albendazole can be decreased when combined with Zucapsaicin.Approved, Vet Approved
AlmotriptanThe metabolism of Almotriptan can be decreased when combined with Zucapsaicin.Approved, Investigational
AlosetronThe metabolism of Alosetron can be decreased when combined with Zucapsaicin.Approved, Withdrawn
AmbrisentanThe metabolism of Ambrisentan can be decreased when combined with Zucapsaicin.Approved, Investigational
AminophenazoneThe metabolism of Aminophenazone can be decreased when combined with Zucapsaicin.Approved, Withdrawn
AminophyllineThe metabolism of Aminophylline can be decreased when combined with Zucapsaicin.Approved
AmiodaroneThe metabolism of Amiodarone can be decreased when combined with Zucapsaicin.Approved, Investigational
AmitriptylineThe metabolism of Amitriptyline can be decreased when combined with Zucapsaicin.Approved
AmoxicillinThe metabolism of Amoxicillin can be decreased when combined with Zucapsaicin.Approved, Vet Approved
AnagrelideThe metabolism of Anagrelide can be decreased when combined with Zucapsaicin.Approved
AntipyrineThe metabolism of Antipyrine can be decreased when combined with Zucapsaicin.Approved
ApixabanThe metabolism of Apixaban can be decreased when combined with Zucapsaicin.Approved
AprepitantThe metabolism of Aprepitant can be decreased when combined with Zucapsaicin.Approved, Investigational
ArformoterolThe metabolism of Arformoterol can be decreased when combined with Zucapsaicin.Approved, Investigational
ArtemetherThe metabolism of Artemether can be decreased when combined with Zucapsaicin.Approved
AsenapineThe metabolism of Asenapine can be decreased when combined with Zucapsaicin.Approved
AtomoxetineThe metabolism of Atomoxetine can be decreased when combined with Zucapsaicin.Approved
AtorvastatinThe risk or severity of adverse effects can be increased when Zucapsaicin is combined with Atorvastatin.Approved
AV650The metabolism of AV650 can be decreased when combined with Zucapsaicin.Approved, Investigational
AxitinibThe metabolism of Axitinib can be decreased when combined with Zucapsaicin.Approved, Investigational
AzelastineThe metabolism of Azelastine can be decreased when combined with Zucapsaicin.Approved
BendamustineThe metabolism of Bendamustine can be decreased when combined with Zucapsaicin.Approved, Investigational
BenzatropineThe metabolism of Benzatropine can be decreased when combined with Zucapsaicin.Approved
Benzyl alcoholThe metabolism of Benzyl alcohol can be decreased when combined with Zucapsaicin.Approved
BetaxololThe metabolism of Betaxolol can be decreased when combined with Zucapsaicin.Approved
BortezomibThe metabolism of Bortezomib can be decreased when combined with Zucapsaicin.Approved, Investigational
BrivaracetamThe metabolism of Brivaracetam can be decreased when combined with Zucapsaicin.Approved, Investigational
BromazepamThe metabolism of Bromazepam can be decreased when combined with Zucapsaicin.Approved, Illicit
BromocriptineThe risk or severity of adverse effects can be increased when Bromocriptine is combined with Zucapsaicin.Approved, Investigational
BrompheniramineThe metabolism of Brompheniramine can be decreased when combined with Zucapsaicin.Approved
BupivacaineThe metabolism of Bupivacaine can be decreased when combined with Zucapsaicin.Approved, Investigational
BupropionThe metabolism of Bupropion can be decreased when combined with Zucapsaicin.Approved
CabergolineThe risk or severity of adverse effects can be increased when Cabergoline is combined with Zucapsaicin.Approved
CaffeineThe metabolism of Caffeine can be decreased when combined with Zucapsaicin.Approved
CarbamazepineThe metabolism of Carbamazepine can be decreased when combined with Zucapsaicin.Approved, Investigational
CarbinoxamineThe metabolism of Carbinoxamine can be decreased when combined with Zucapsaicin.Approved
CarisoprodolThe metabolism of Carisoprodol can be decreased when combined with Zucapsaicin.Approved
CarmustineThe metabolism of Carmustine can be decreased when combined with Zucapsaicin.Approved
CarvedilolThe metabolism of Carvedilol can be decreased when combined with Zucapsaicin.Approved, Investigational
CerivastatinThe serum concentration of Cerivastatin can be increased when it is combined with Zucapsaicin.Withdrawn
ChloramphenicolThe metabolism of Chloramphenicol can be decreased when combined with Zucapsaicin.Approved, Vet Approved
ChlorpromazineThe metabolism of Chlorpromazine can be decreased when combined with Zucapsaicin.Approved, Vet Approved
ChlorpropamideThe metabolism of Chlorpropamide can be decreased when combined with Zucapsaicin.Approved
ChlorzoxazoneThe metabolism of Chlorzoxazone can be decreased when combined with Zucapsaicin.Approved
CilostazolThe serum concentration of Cilostazol can be increased when it is combined with Zucapsaicin.Approved
CinacalcetThe metabolism of Cinacalcet can be decreased when combined with Zucapsaicin.Approved
CinnarizineThe metabolism of Cinnarizine can be decreased when combined with Zucapsaicin.Approved
CisaprideThe metabolism of Cisapride can be decreased when combined with Zucapsaicin.Approved, Investigational, Withdrawn
CitalopramThe serum concentration of Citalopram can be increased when it is combined with Zucapsaicin.Approved
ClarithromycinThe metabolism of Clarithromycin can be decreased when combined with Zucapsaicin.Approved
ClenbuterolThe metabolism of Clenbuterol can be decreased when combined with Zucapsaicin.Approved, Vet Approved
ClevidipineThe metabolism of Clevidipine can be decreased when combined with Zucapsaicin.Approved
ClobazamThe metabolism of Clobazam can be decreased when combined with Zucapsaicin.Approved, Illicit
clomethiazoleThe metabolism of clomethiazole can be decreased when combined with Zucapsaicin.Investigational
ClomipramineThe metabolism of Clomipramine can be decreased when combined with Zucapsaicin.Approved, Vet Approved
ClonidineThe metabolism of Clonidine can be decreased when combined with Zucapsaicin.Approved
ClopidogrelThe serum concentration of the active metabolites of Clopidogrel can be reduced when Clopidogrel is used in combination with Zucapsaicin resulting in a loss in efficacy.Approved, Nutraceutical
ClotiazepamThe metabolism of Clotiazepam can be decreased when combined with Zucapsaicin.Approved, Illicit
ClozapineThe metabolism of Clozapine can be decreased when combined with Zucapsaicin.Approved
Conjugated estrogensThe metabolism of Conjugated estrogens can be decreased when combined with Zucapsaicin.Approved
CyclobenzaprineThe metabolism of Cyclobenzaprine can be decreased when combined with Zucapsaicin.Approved
CyclophosphamideThe metabolism of Cyclophosphamide can be decreased when combined with Zucapsaicin.Approved, Investigational
DacarbazineThe metabolism of Dacarbazine can be decreased when combined with Zucapsaicin.Approved, Investigational
DapagliflozinThe metabolism of Dapagliflozin can be decreased when combined with Zucapsaicin.Approved
DapsoneThe metabolism of Dapsone can be decreased when combined with Zucapsaicin.Approved, Investigational
DasatinibThe metabolism of Dasatinib can be decreased when combined with Zucapsaicin.Approved, Investigational
DaunorubicinThe metabolism of Daunorubicin can be decreased when combined with Zucapsaicin.Approved
DesipramineThe metabolism of Desipramine can be decreased when combined with Zucapsaicin.Approved
DeutetrabenazineThe metabolism of Deutetrabenazine can be decreased when combined with Zucapsaicin.Approved, Investigational
DexfenfluramineThe metabolism of Dexfenfluramine can be decreased when combined with Zucapsaicin.Approved, Illicit, Withdrawn
DexlansoprazoleThe metabolism of Dexlansoprazole can be decreased when combined with Zucapsaicin.Approved
DextromethorphanThe metabolism of Dextromethorphan can be decreased when combined with Zucapsaicin.Approved
DiazepamThe metabolism of Diazepam can be decreased when combined with Zucapsaicin.Approved, Illicit, Vet Approved
DiclofenacThe metabolism of Diclofenac can be decreased when combined with Zucapsaicin.Approved, Vet Approved
DihydroergocornineThe risk or severity of adverse effects can be increased when Dihydroergocornine is combined with Zucapsaicin.Approved
DihydroergocristineThe risk or severity of adverse effects can be increased when Dihydroergocristine is combined with Zucapsaicin.Experimental
DihydroergocryptineThe risk or severity of adverse effects can be increased when Dihydroergocryptine is combined with Zucapsaicin.Experimental
DihydroergotamineThe risk or severity of adverse effects can be increased when Dihydroergotamine is combined with Zucapsaicin.Approved
DiltiazemThe metabolism of Diltiazem can be decreased when combined with Zucapsaicin.Approved
DinoprostoneThe metabolism of Dinoprostone can be decreased when combined with Zucapsaicin.Approved
DiphenhydramineThe metabolism of Diphenhydramine can be decreased when combined with Zucapsaicin.Approved
DomperidoneThe metabolism of Domperidone can be decreased when combined with Zucapsaicin.Approved, Investigational, Vet Approved
DopamineThe metabolism of Dopamine can be decreased when combined with Zucapsaicin.Approved
DoxazosinThe metabolism of Doxazosin can be decreased when combined with Zucapsaicin.Approved
DoxepinThe metabolism of Doxepin can be decreased when combined with Zucapsaicin.Approved
DronabinolThe metabolism of Dronabinol can be decreased when combined with Zucapsaicin.Approved, Illicit
DuloxetineThe metabolism of Duloxetine can be decreased when combined with Zucapsaicin.Approved
EletriptanThe metabolism of Eletriptan can be decreased when combined with Zucapsaicin.Approved, Investigational
EltrombopagThe metabolism of Eltrombopag can be decreased when combined with Zucapsaicin.Approved
EnasidenibThe metabolism of Enasidenib can be decreased when combined with Zucapsaicin.Approved
EnfuvirtideThe metabolism of Enfuvirtide can be decreased when combined with Zucapsaicin.Approved, Investigational
ErgonovineThe risk or severity of adverse effects can be increased when Ergonovine is combined with Zucapsaicin.Approved
ErgotamineThe metabolism of Ergotamine can be decreased when combined with Zucapsaicin.Approved
ErlotinibThe metabolism of Erlotinib can be decreased when combined with Zucapsaicin.Approved, Investigational
EscitalopramThe metabolism of Escitalopram can be decreased when combined with Zucapsaicin.Approved, Investigational
EsomeprazoleThe metabolism of Esomeprazole can be decreased when combined with Zucapsaicin.Approved, Investigational
EstradiolThe metabolism of Estradiol can be decreased when combined with Zucapsaicin.Approved, Investigational, Vet Approved
EstroneThe metabolism of Estrone can be decreased when combined with Zucapsaicin.Approved
Estrone sulfateThe metabolism of Estrone sulfate can be decreased when combined with Zucapsaicin.Approved
EthanolThe metabolism of Ethanol can be decreased when combined with Zucapsaicin.Approved
EtizolamThe metabolism of Etizolam can be decreased when combined with Zucapsaicin.Approved
EtoposideThe metabolism of Etoposide can be decreased when combined with Zucapsaicin.Approved
EtoricoxibThe metabolism of Etoricoxib can be decreased when combined with Zucapsaicin.Approved, Investigational
EtravirineThe metabolism of Etravirine can be decreased when combined with Zucapsaicin.Approved
FamotidineThe metabolism of Famotidine can be decreased when combined with Zucapsaicin.Approved
FesoterodineThe serum concentration of the active metabolites of Fesoterodine can be increased when Fesoterodine is used in combination with Zucapsaicin.Approved
FlunarizineThe metabolism of Flunarizine can be decreased when combined with Zucapsaicin.Approved
FlunitrazepamThe metabolism of Flunitrazepam can be decreased when combined with Zucapsaicin.Approved, Illicit
FluorouracilThe metabolism of Fluorouracil can be decreased when combined with Zucapsaicin.Approved
FluoxetineThe metabolism of Fluoxetine can be decreased when combined with Zucapsaicin.Approved, Vet Approved
FlutamideThe metabolism of Flutamide can be decreased when combined with Zucapsaicin.Approved
FluvastatinThe serum concentration of Fluvastatin can be increased when it is combined with Zucapsaicin.Approved
FluvoxamineThe metabolism of Fluvoxamine can be decreased when combined with Zucapsaicin.Approved, Investigational
FormoterolThe metabolism of Formoterol can be decreased when combined with Zucapsaicin.Approved, Investigational
FosphenytoinThe metabolism of Fosphenytoin can be decreased when combined with Zucapsaicin.Approved
FrovatriptanThe metabolism of Frovatriptan can be decreased when combined with Zucapsaicin.Approved, Investigational
GenisteinThe metabolism of Genistein can be decreased when combined with Zucapsaicin.Investigational
GliclazideThe metabolism of Gliclazide can be decreased when combined with Zucapsaicin.Approved
GlucosamineThe metabolism of Glucosamine can be decreased when combined with Zucapsaicin.Approved
GlyburideThe metabolism of Glyburide can be decreased when combined with Zucapsaicin.Approved
GrepafloxacinThe metabolism of Grepafloxacin can be decreased when combined with Zucapsaicin.Withdrawn
GuanabenzThe metabolism of Guanabenz can be decreased when combined with Zucapsaicin.Approved
GuanfacineThe metabolism of Guanfacine can be decreased when combined with Zucapsaicin.Approved, Investigational
HaloperidolThe metabolism of Haloperidol can be decreased when combined with Zucapsaicin.Approved
HesperetinThe metabolism of Hesperetin can be decreased when combined with Zucapsaicin.Approved
HexobarbitalThe metabolism of Hexobarbital can be decreased when combined with Zucapsaicin.Approved
IbuprofenThe metabolism of Ibuprofen can be decreased when combined with Zucapsaicin.Approved
IcotinibThe metabolism of Icotinib can be decreased when combined with Zucapsaicin.Approved, Investigational
IfosfamideThe metabolism of Ifosfamide can be decreased when combined with Zucapsaicin.Approved
IloperidoneThe metabolism of Iloperidone can be decreased when combined with Zucapsaicin.Approved
ImatinibThe metabolism of Imatinib can be decreased when combined with Zucapsaicin.Approved
ImipramineThe metabolism of Imipramine can be decreased when combined with Zucapsaicin.Approved
ImiquimodThe metabolism of Imiquimod can be decreased when combined with Zucapsaicin.Approved, Investigational
IndomethacinThe metabolism of Indomethacin can be decreased when combined with Zucapsaicin.Approved, Investigational
IxazomibThe metabolism of Ixazomib can be decreased when combined with Zucapsaicin.Approved
KetobemidoneThe metabolism of Ketobemidone can be decreased when combined with Zucapsaicin.Approved
LansoprazoleThe metabolism of Lansoprazole can be decreased when combined with Zucapsaicin.Approved, Investigational
LapatinibThe metabolism of Lapatinib can be decreased when combined with Zucapsaicin.Approved, Investigational
LeflunomideThe metabolism of Leflunomide can be decreased when combined with Zucapsaicin.Approved, Investigational
LevobupivacaineThe metabolism of Levobupivacaine can be decreased when combined with Zucapsaicin.Approved
LevomilnacipranThe metabolism of Levomilnacipran can be decreased when combined with Zucapsaicin.Approved
LidocaineThe metabolism of Lidocaine can be decreased when combined with Zucapsaicin.Approved, Vet Approved
LisurideThe risk or severity of adverse effects can be increased when Lisuride is combined with Zucapsaicin.Approved
LomefloxacinThe metabolism of Lomefloxacin can be decreased when combined with Zucapsaicin.Approved
LorcaserinThe metabolism of Lorcaserin can be decreased when combined with Zucapsaicin.Approved
LovastatinThe serum concentration of Lovastatin can be increased when it is combined with Zucapsaicin.Approved, Investigational
LumiracoxibThe metabolism of Lumiracoxib can be decreased when combined with Zucapsaicin.Approved, Investigational
Lysergic Acid DiethylamideThe risk or severity of adverse effects can be increased when Lysergic Acid Diethylamide is combined with Zucapsaicin.Illicit, Withdrawn
MacitentanThe metabolism of Macitentan can be decreased when combined with Zucapsaicin.Approved
MalathionThe metabolism of Malathion can be decreased when combined with Zucapsaicin.Approved, Investigational
MaprotilineThe metabolism of Maprotiline can be decreased when combined with Zucapsaicin.Approved
MelatoninThe metabolism of Melatonin can be decreased when combined with Zucapsaicin.Approved, Nutraceutical, Vet Approved
MenadioneThe metabolism of Menadione can be decreased when combined with Zucapsaicin.Approved, Nutraceutical
MephenytoinThe metabolism of Mephenytoin can be decreased when combined with Zucapsaicin.Investigational, Withdrawn
MeprobamateThe metabolism of Meprobamate can be decreased when combined with Zucapsaicin.Approved, Illicit
MetergolineThe risk or severity of adverse effects can be increased when Metergoline is combined with Zucapsaicin.Experimental
MethadoneThe metabolism of Methadone can be decreased when combined with Zucapsaicin.Approved
MethoxyfluraneThe metabolism of Methoxyflurane can be decreased when combined with Zucapsaicin.Approved, Vet Approved
MethsuximideThe metabolism of Methsuximide can be decreased when combined with Zucapsaicin.Approved
MethylergometrineThe risk or severity of adverse effects can be increased when Methylergometrine is combined with Zucapsaicin.Approved
MethylphenobarbitalThe metabolism of Methylphenobarbital can be decreased when combined with Zucapsaicin.Approved
MethysergideThe risk or severity of adverse effects can be increased when Methysergide is combined with Zucapsaicin.Approved
MetoprololThe serum concentration of Metoprolol can be increased when it is combined with Zucapsaicin.Approved, Investigational
MevastatinThe serum concentration of Mevastatin can be increased when it is combined with Zucapsaicin.Experimental
MexiletineThe metabolism of Mexiletine can be decreased when combined with Zucapsaicin.Approved
MianserinThe metabolism of Mianserin can be decreased when combined with Zucapsaicin.Approved
MirtazapineThe metabolism of Mirtazapine can be decreased when combined with Zucapsaicin.Approved
MoclobemideThe metabolism of Moclobemide can be decreased when combined with Zucapsaicin.Approved
muraglitazarThe metabolism of muraglitazar can be decreased when combined with Zucapsaicin.Investigational
NabumetoneThe metabolism of Nabumetone can be decreased when combined with Zucapsaicin.Approved
NaproxenThe metabolism of Naproxen can be decreased when combined with Zucapsaicin.Approved, Vet Approved
NelfinavirThe metabolism of Nelfinavir can be decreased when combined with Zucapsaicin.Approved
NicergolineThe risk or severity of adverse effects can be increased when Nicergoline is combined with Zucapsaicin.Approved
NicotineThe metabolism of Nicotine can be decreased when combined with Zucapsaicin.Approved
NifedipineThe metabolism of Nifedipine can be decreased when combined with Zucapsaicin.Approved
NilutamideThe metabolism of Nilutamide can be decreased when combined with Zucapsaicin.Approved
Nitric OxideThe metabolism of Nitric Oxide can be decreased when combined with Zucapsaicin.Approved
NortriptylineThe metabolism of Nortriptyline can be decreased when combined with Zucapsaicin.Approved
OlanzapineThe metabolism of Olanzapine can be decreased when combined with Zucapsaicin.Approved, Investigational
OmeprazoleThe metabolism of Omeprazole can be decreased when combined with Zucapsaicin.Approved, Investigational, Vet Approved
OndansetronThe metabolism of Ondansetron can be decreased when combined with Zucapsaicin.Approved
OspemifeneThe metabolism of Ospemifene can be decreased when combined with Zucapsaicin.Approved
OxaliplatinThe metabolism of Oxaliplatin can be decreased when combined with Zucapsaicin.Approved, Investigational
OxiconazoleThe metabolism of Oxiconazole can be decreased when combined with Zucapsaicin.Approved
OxtriphyllineThe metabolism of Oxtriphylline can be decreased when combined with Zucapsaicin.Approved
PalonosetronThe metabolism of Palonosetron can be decreased when combined with Zucapsaicin.Approved, Investigational
PantoprazoleThe metabolism of Pantoprazole can be decreased when combined with Zucapsaicin.Approved
PazopanibThe metabolism of Pazopanib can be decreased when combined with Zucapsaicin.Approved
PentamidineThe metabolism of Pentamidine can be decreased when combined with Zucapsaicin.Approved
PentobarbitalThe metabolism of Pentobarbital can be decreased when combined with Zucapsaicin.Approved, Vet Approved
PentoxifyllineThe metabolism of Pentoxifylline can be decreased when combined with Zucapsaicin.Approved, Investigational
PergolideThe risk or severity of adverse effects can be increased when Pergolide is combined with Zucapsaicin.Approved, Vet Approved, Withdrawn
PerphenazineThe metabolism of Perphenazine can be decreased when combined with Zucapsaicin.Approved
PethidineThe metabolism of Pethidine can be decreased when combined with Zucapsaicin.Approved
PhenacetinThe metabolism of Phenacetin can be decreased when combined with Zucapsaicin.Withdrawn
PhenobarbitalThe metabolism of Phenobarbital can be decreased when combined with Zucapsaicin.Approved
PhenytoinThe metabolism of Phenytoin can be decreased when combined with Zucapsaicin.Approved, Vet Approved
PimozideThe metabolism of Pimozide can be decreased when combined with Zucapsaicin.Approved
PipotiazineThe metabolism of Pipotiazine can be decreased when combined with Zucapsaicin.Approved
PirfenidoneThe serum concentration of Pirfenidone can be increased when it is combined with Zucapsaicin.Investigational
PitavastatinThe serum concentration of Pitavastatin can be increased when it is combined with Zucapsaicin.Approved
PodofiloxThe metabolism of Podofilox can be decreased when combined with Zucapsaicin.Approved
PomalidomideThe metabolism of Pomalidomide can be decreased when combined with Zucapsaicin.Approved
PrasugrelThe metabolism of Prasugrel can be decreased when combined with Zucapsaicin.Approved
PravastatinThe serum concentration of Pravastatin can be increased when it is combined with Zucapsaicin.Approved
PraziquantelThe metabolism of Praziquantel can be decreased when combined with Zucapsaicin.Approved, Vet Approved
PrimaquineThe metabolism of Primaquine can be decreased when combined with Zucapsaicin.Approved
PrimidoneThe metabolism of Primidone can be decreased when combined with Zucapsaicin.Approved, Vet Approved
ProgesteroneThe metabolism of Progesterone can be decreased when combined with Zucapsaicin.Approved, Vet Approved
ProguanilThe metabolism of Proguanil can be decreased when combined with Zucapsaicin.Approved
PromazineThe metabolism of Promazine can be decreased when combined with Zucapsaicin.Approved, Vet Approved
PropafenoneThe metabolism of Propafenone can be decreased when combined with Zucapsaicin.Approved
PropofolThe metabolism of Propofol can be decreased when combined with Zucapsaicin.Approved, Investigational, Vet Approved
PropranololThe metabolism of Propranolol can be decreased when combined with Zucapsaicin.Approved, Investigational
PyrazinamideThe metabolism of Pyrazinamide can be decreased when combined with Zucapsaicin.Approved
QuazepamThe metabolism of Quazepam can be decreased when combined with Zucapsaicin.Approved, Illicit
QuetiapineThe metabolism of Quetiapine can be decreased when combined with Zucapsaicin.Approved
QuinineThe metabolism of Quinine can be decreased when combined with Zucapsaicin.Approved
RabeprazoleThe metabolism of Rabeprazole can be decreased when combined with Zucapsaicin.Approved, Investigational
RamelteonThe metabolism of Ramelteon can be decreased when combined with Zucapsaicin.Approved, Investigational
RanitidineThe metabolism of Ranitidine can be decreased when combined with Zucapsaicin.Approved
RasagilineThe metabolism of Rasagiline can be decreased when combined with Zucapsaicin.Approved
ResveratrolThe metabolism of Resveratrol can be decreased when combined with Zucapsaicin.Experimental, Investigational
RifabutinThe metabolism of Rifabutin can be decreased when combined with Zucapsaicin.Approved
RiluzoleThe metabolism of Riluzole can be decreased when combined with Zucapsaicin.Approved, Investigational
RitonavirThe metabolism of Ritonavir can be decreased when combined with Zucapsaicin.Approved, Investigational
RizatriptanThe metabolism of Rizatriptan can be decreased when combined with Zucapsaicin.Approved
RofecoxibThe metabolism of Rofecoxib can be decreased when combined with Zucapsaicin.Investigational, Withdrawn
RomidepsinThe metabolism of Romidepsin can be decreased when combined with Zucapsaicin.Approved, Investigational
RopiniroleThe metabolism of Ropinirole can be decreased when combined with Zucapsaicin.Approved, Investigational
RopivacaineThe metabolism of Ropivacaine can be decreased when combined with Zucapsaicin.Approved
RosuvastatinThe metabolism of Rosuvastatin can be decreased when combined with Zucapsaicin.Approved
RotigotineThe metabolism of Rotigotine can be decreased when combined with Zucapsaicin.Approved
RucaparibThe metabolism of Rucaparib can be decreased when combined with Zucapsaicin.Approved, Investigational
RupatadineThe metabolism of Rupatadine can be decreased when combined with Zucapsaicin.Approved
SelegilineThe metabolism of Selegiline can be decreased when combined with Zucapsaicin.Approved, Investigational, Vet Approved
SeratrodastThe metabolism of Seratrodast can be decreased when combined with Zucapsaicin.Approved
SertralineThe metabolism of Sertraline can be decreased when combined with Zucapsaicin.Approved
SildenafilThe metabolism of Sildenafil can be decreased when combined with Zucapsaicin.Approved, Investigational
SimvastatinThe serum concentration of Simvastatin can be increased when it is combined with Zucapsaicin.Approved
StiripentolThe metabolism of Stiripentol can be decreased when combined with Zucapsaicin.Approved
TacrineThe metabolism of Tacrine can be decreased when combined with Zucapsaicin.Withdrawn
TamoxifenThe metabolism of Tamoxifen can be decreased when combined with Zucapsaicin.Approved
TapentadolThe metabolism of Tapentadol can be decreased when combined with Zucapsaicin.Approved
TelithromycinThe metabolism of Telithromycin can be decreased when combined with Zucapsaicin.Approved
TemafloxacinThe metabolism of Temafloxacin can be decreased when combined with Zucapsaicin.Withdrawn
TemazepamThe metabolism of Temazepam can be decreased when combined with Zucapsaicin.Approved
TeniposideThe metabolism of Teniposide can be decreased when combined with Zucapsaicin.Approved
TerbinafineThe metabolism of Terbinafine can be decreased when combined with Zucapsaicin.Approved, Investigational, Vet Approved
TergurideThe risk or severity of adverse effects can be increased when Terguride is combined with Zucapsaicin.Experimental
TestosteroneThe metabolism of Testosterone can be decreased when combined with Zucapsaicin.Approved, Investigational
ThalidomideThe metabolism of Thalidomide can be decreased when combined with Zucapsaicin.Approved, Investigational, Withdrawn
TheobromineThe metabolism of Theobromine can be decreased when combined with Zucapsaicin.Approved
TheophyllineThe metabolism of Theophylline can be decreased when combined with Zucapsaicin.Approved
ThiabendazoleThe metabolism of Thiabendazole can be decreased when combined with Zucapsaicin.Approved, Vet Approved
ThioridazineThe serum concentration of Thioridazine can be increased when it is combined with Zucapsaicin.Withdrawn
ThiothixeneThe metabolism of Thiothixene can be decreased when combined with Zucapsaicin.Approved
TiclopidineThe metabolism of Ticlopidine can be decreased when combined with Zucapsaicin.Approved
TimololThe metabolism of Timolol can be decreased when combined with Zucapsaicin.Approved
TipranavirThe metabolism of Tipranavir can be decreased when combined with Zucapsaicin.Approved, Investigational
TizanidineThe serum concentration of Tizanidine can be increased when it is combined with Zucapsaicin.Approved
TofacitinibThe metabolism of Tofacitinib can be decreased when combined with Zucapsaicin.Approved, Investigational
TolbutamideThe metabolism of Tolbutamide can be decreased when combined with Zucapsaicin.Approved
TolterodineThe metabolism of Tolterodine can be decreased when combined with Zucapsaicin.Approved, Investigational
ToremifeneThe metabolism of Toremifene can be decreased when combined with Zucapsaicin.Approved, Investigational
TrabectedinThe metabolism of Trabectedin can be decreased when combined with Zucapsaicin.Approved, Investigational
TriamtereneThe metabolism of Triamterene can be decreased when combined with Zucapsaicin.Approved
TrifluoperazineThe metabolism of Trifluoperazine can be decreased when combined with Zucapsaicin.Approved
TrimethadioneThe metabolism of Trimethadione can be decreased when combined with Zucapsaicin.Approved
TrimipramineThe metabolism of Trimipramine can be decreased when combined with Zucapsaicin.Approved
TroglitazoneThe metabolism of Troglitazone can be decreased when combined with Zucapsaicin.Withdrawn
UbidecarenoneThe serum concentration of Ubidecarenone can be increased when it is combined with Zucapsaicin.Experimental
UlipristalThe metabolism of Ulipristal can be decreased when combined with Zucapsaicin.Approved
VadimezanThe metabolism of Vadimezan can be decreased when combined with Zucapsaicin.Investigational
Valproic AcidThe metabolism of Valproic Acid can be decreased when combined with Zucapsaicin.Approved, Investigational
VenlafaxineThe metabolism of Venlafaxine can be decreased when combined with Zucapsaicin.Approved
VerapamilThe metabolism of Verapamil can be decreased when combined with Zucapsaicin.Approved
VoriconazoleThe metabolism of Voriconazole can be decreased when combined with Zucapsaicin.Approved, Investigational
VortioxetineThe metabolism of Vortioxetine can be decreased when combined with Zucapsaicin.Approved
VoxilaprevirThe metabolism of Voxilaprevir can be decreased when combined with Zucapsaicin.Approved
WarfarinThe metabolism of Warfarin can be decreased when combined with Zucapsaicin.Approved
ZidovudineThe metabolism of Zidovudine can be decreased when combined with Zucapsaicin.Approved
ZileutonThe metabolism of Zileuton can be decreased when combined with Zucapsaicin.Approved, Investigational, Withdrawn
ZiprasidoneThe metabolism of Ziprasidone can be decreased when combined with Zucapsaicin.Approved
ZolmitriptanThe metabolism of Zolmitriptan can be decreased when combined with Zucapsaicin.Approved, Investigational
ZolpidemThe metabolism of Zolpidem can be decreased when combined with Zucapsaicin.Approved
Food Interactions
Not Available

References

Synthesis Reference
  1. Gannett PM, Nagel DL, Reilly PJ, Lawson T, Sharpe J, Toth B: The Capsaicinoids: Their Separation, Synthesis, and Mutagenicity. J. Org. Chem., 1988, 53 (5), pp 1064–1071.
  2. Kaga H, Miura M, Orito K: A facile procedure for synthesis of capsaicin. J. Org. Chem., 1989, 54 (14), pp 3477–3478.
General References
  1. Salat K, Jakubowska A, Kulig K: Zucapsaicin for the treatment of neuropathic pain. Expert Opin Investig Drugs. 2014 Oct;23(10):1433-40. doi: 10.1517/13543784.2014.956079. Epub 2014 Aug 29. [PubMed:25171227]
  2. Derry S, Lloyd R, Moore RA, McQuay HJ: Topical capsaicin for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD007393. doi: 10.1002/14651858.CD007393.pub2. [PubMed:19821411]
  3. Studer M, McNaughton PA: Modulation of single-channel properties of TRPV1 by phosphorylation. J Physiol. 2010 Oct 1;588(Pt 19):3743-56. doi: 10.1113/jphysiol.2010.190611. Epub 2010 Aug 6. [PubMed:20693293]
  4. Rosenbaum T, Simon SA: TRPV1 Receptors and Signal Transduction . [PubMed:21204507]
  5. Sanofi Canada: ZUACTA (zucapsaicin cream) product monograph [Link]
External Links
PubChem Compound
1548942
PubChem Substance
310265037
ChemSpider
1265956
ChEBI
135952
ChEMBL
CHEMBL313971
ATC Codes
M02AB02 — Zucapsaicin
AHFS Codes
  • 28:08.04.92 — Other Nonsteroidal Antiimflammatory Agents

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceHealthy Volunteers1
1TerminatedBasic ScienceHealthy Volunteers1
2CompletedTreatmentPostherpetic Neuralgia1
3CompletedTreatmentEpisodic Cluster Headache2
3CompletedTreatmentOsteoarthritis of the Knees2
3Not Yet RecruitingPreventionEpisodic Cluster Headache1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
CreamTopical0.075 %
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)71.5-74.5Product monograph
water solubilityInsolubleProduct monograph
Predicted Properties
PropertyValueSource
Water Solubility0.00841 mg/mLALOGPS
logP3.8ALOGPS
logP3.75ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)9.93ChemAxon
pKa (Strongest Basic)-0.52ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area58.56 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity90.32 m3·mol-1ChemAxon
Polarizability35.34 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

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
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000i-1900000000-b2bcbe6ef314218a9fca

Taxonomy

Description
This compound belongs to the class of organic compounds known as methoxyphenols. These are compounds containing a methoxy group attached to the benzene ring of a phenol moiety.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Phenols
Sub Class
Methoxyphenols
Direct Parent
Methoxyphenols
Alternative Parents
Phenoxy compounds / Methoxybenzenes / Anisoles / Alkyl aryl ethers / 1-hydroxy-2-unsubstituted benzenoids / N-acyl amines / Secondary carboxylic acid amides / Organopnictogen compounds / Organonitrogen compounds / Organic oxides
show 2 more
Substituents
Methoxyphenol / Phenoxy compound / Anisole / Methoxybenzene / Phenol ether / Alkyl aryl ether / 1-hydroxy-2-unsubstituted benzenoid / Monocyclic benzene moiety / Fatty acyl / Fatty amide
show 14 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
Activator
General Function
Transmembrane signaling receptor activity
Specific Function
Ligand-activated non-selective calcium permeant cation channel involved in detection of noxious chemical and thermal stimuli. Seems to mediate proton influx and may be involved in intracellular aci...
Gene Name
TRPV1
Uniprot ID
Q8NER1
Uniprot Name
Transient receptor potential cation channel subfamily V member 1
Molecular Weight
94955.33 Da
References
  1. Yang F, Xiao X, Cheng W, Yang W, Yu P, Song Z, Yarov-Yarovoy V, Zheng J: Structural mechanism underlying capsaicin binding and activation of the TRPV1 ion channel. Nat Chem Biol. 2015 Jul;11(7):518-24. doi: 10.1038/nchembio.1835. Epub 2015 Jun 8. [PubMed:26053297]
  2. Smutzer G, Devassy RK: Integrating TRPV1 Receptor Function with Capsaicin Psychophysics. Adv Pharmacol Sci. 2016;2016:1512457. doi: 10.1155/2016/1512457. Epub 2016 Jan 14. [PubMed:26884754]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Sanofi Canada: ZUACTA (zucapsaicin cream) product monograph [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Sanofi Canada: ZUACTA (zucapsaicin cream) product monograph [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Sanofi Canada: ZUACTA (zucapsaicin cream) product monograph [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Sanofi Canada: ZUACTA (zucapsaicin cream) product monograph [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Sanofi Canada: ZUACTA (zucapsaicin cream) product monograph [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Sanofi Canada: ZUACTA (zucapsaicin cream) product monograph [Link]

Drug created on September 22, 2015 15:09 / Updated on October 21, 2017 09:34