Identification
- Summary
Zucapsaicin is a topical analgesic used as an adjunct to relieve severe pain of osteoarthritis of the knee in selected adult patients.
- Generic Name
- Zucapsaicin
- DrugBank Accession Number
- DB09120
- Background
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 evaluated for the management of several conditions manifested by chronic nerve pain. These conditions include herpes simplex (HSV) infections, cluster headaches, migraine, and osteoarthritis of the knee. Zucapsaicin was approved by the Health Canada in 2010 as topical cream marketed under the brand name Zuacta but currently not FDA-approved.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Zucapsaicin (DB09120)
- Weight
- Average: 305.4119
Monoisotopic: 305.199093735 - Chemical Formula
- C18H27NO3
- Synonyms
- (Z)-Capsaicin
- cis-Capsaicin
- Civamide
- Zucapsaicin
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.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Adjunct therapy in treatment of Severe pain •••••••••••• ••••• Adjunct therapy in treatment of Severe pain •••••••••••• ••••• Used in combination to treat Severe pain •••••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- 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.
Target Actions Organism ATransient receptor potential cation channel subfamily V member 1 agonistactivatorHumans - 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
- Adverse Effects
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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.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareBelzutifan The serum concentration of Belzutifan can be increased when it is combined with Zucapsaicin. Clobazam The serum concentration of Clobazam can be increased when it is combined with Zucapsaicin. Fezolinetant The serum concentration of Fezolinetant can be increased when it is combined with Zucapsaicin. Mavacamten The serum concentration of Mavacamten can be increased when it is combined with Zucapsaicin. Pirfenidone The metabolism of Pirfenidone can be decreased when combined with Zucapsaicin. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Civanex
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Zuacta Cream 0.075 % w/w Topical Sanofi Aventis 2011-08-24 2020-07-17 Canada 
Categories
- ATC Codes
- M02AB02 — Zucapsaicin
- Drug Categories
- Alkaloids
- Alkenes
- Alkynes
- Amides
- Analgesics
- Benzene Derivatives
- Capsaicin and Similar Agents
- Catechols
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors (moderate)
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 Inhibitors (moderate)
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (weak)
- Cytochrome P-450 CYP2E1 Inhibitors
- Cytochrome P-450 CYP2E1 Inhibitors (weak)
- Cytochrome P-450 Enzyme Inhibitors
- Fatty Acids
- Fatty Acids, Monounsaturated
- Fatty Acids, Unsaturated
- Hydrocarbons, Acyclic
- Lipids
- Musculo-Skeletal System
- Other Nonsteroidal Anti-inflammatory Agents
- Phenols
- Polyunsaturated Alkamides
- Solanaceous Alkaloids
- Topical Products for Joint and Muscular Pain
- Chemical TaxonomyProvided by Classyfire
- 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
- 1-hydroxy-2-unsubstituted benzenoid / Alkyl aryl ether / Anisole / Aromatic homomonocyclic compound / Carbonyl group / Carboxamide group / Carboxylic acid derivative / Ether / Fatty acyl / Fatty amide show 14 more
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 15OX67P384
- CAS number
- 25775-90-0
- 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
References
- Synthesis Reference
- 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.
- Kaga H, Miura M, Orito K: A facile procedure for synthesis of capsaicin. J. Org. Chem., 1989, 54 (14), pp 3477–3478.
- General References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Rosenbaum T, Simon SA: TRPV1 Receptors and Signal Transduction . [Article]
- Health Canada Product Monograph: Zuacta (zucapsaicin) topical cream [Link]
- External Links
- PubChem Compound
- 1548942
- PubChem Substance
- 310265037
- ChemSpider
- 1265956
- ChEBI
- 135952
- ChEMBL
- CHEMBL313971
- ZINC
- ZINC000004468952
- Wikipedia
- Zucapsaicin
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Completed Treatment Episodic Cluster Headache 2 3 Completed Treatment Osteoarthritis of the Knee 2 3 Not Yet Recruiting Prevention Episodic Cluster Headache 1 2 Completed Treatment Dry Eyes 1 2 Completed Treatment Postherpetic Neuralgia 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Cream Topical 0.075 % w/w - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 71.5-74.5 Product monograph water solubility Insoluble Product monograph - Predicted Properties
Property Value Source Water Solubility 0.00841 mg/mL ALOGPS logP 3.8 ALOGPS logP 3.75 Chemaxon logS -4.6 ALOGPS pKa (Strongest Acidic) 9.93 Chemaxon pKa (Strongest Basic) -1.4 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 58.56 Å2 Chemaxon Rotatable Bond Count 9 Chemaxon Refractivity 90.32 m3·mol-1 Chemaxon Polarizability 35.34 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
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 201.799676 predictedDarkChem Lite v0.1.0 [M-H]- 180.55632 predictedDeepCCS 1.0 (2019) [M+H]+ 202.371676 predictedDarkChem Lite v0.1.0 [M+H]+ 183.1008 predictedDeepCCS 1.0 (2019) [M+Na]+ 201.807676 predictedDarkChem Lite v0.1.0 [M+Na]+ 190.95708 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AgonistActivator
- 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
- 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. [Article]
- 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. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- 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
- Health Canada Product Monograph: Zuacta (zucapsaicin) topical cream [Link]
- Kind
- Protein
- Organism
- Humans
- 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
- Zuacta Monograph [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Enzyme action is based on in vitro data. There is limited information in the literature supporting this enzyme action, however, the monograph indicates this enzyme action.
- 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
- Zuacta Monograph [File]
- Kind
- Protein
- Organism
- Humans
- 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
Drug created at September 22, 2015 21:09 / Updated at February 20, 2024 23:55