Nicoboxil is a medication used to treat acute back pain.
- Generic Name
- DrugBank Accession Number
Nicoboxil has been investigated for the treatment of Acute Low Back Pain, where it is typically considered an effective and safe therapeutic option. Nevertheless, it is predominantly found paired with nonivamide as a combination topical analgesic product where its proposed mechanism of action as a rubefacient is complementary and ultimately synergistic with nonivamide's capsaicin activity 5. Such combination topical analgesics are only available for purchase and use (for humans) in some parts of Europe and Asia, like Germany and Australia 5,7.
Despite topical nicoboxil/nonivamide topical analgesic medication being used since the 1950s, recent studies demonstrate continued interest in the medication(s) given its demonstrated efficacy, safety, and capability to be used as an alternative musculoskeletal pain therapy option with less systemic side effects when compared to the oral non-steroidal anti-inflammatory drugs and opioids that may be more typically prescribed 1,2.
- Small Molecule
- Approved, Investigational
- Average: 223.272
- Chemical Formula
- beta-Butoxyethyl nicotinate
The primary therapeutic use for which nicoboxil is currently indicated for is as an active ingredient in combination with the capsaicinoid nonivamide compound as a topical analgesic for the temporary relief of the pain of rheumatism, arthritis, lumbago, muscular aches, sprains and strains, sporting injuries, and other conditions where local warmth is beneficial 5.
Nevertheless, most of the available studies regarding the use of nicoboxil and nonivamide topical analgesics focus specifically on their efficacy and safety in treating acute non-specific low back pain, typically finding the combination analgesic to be an effective, safe, and well-tolerated medication for such an indication 1,2.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.
- 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
Topical applications consisting of the individual active ingredients of nicoboxil and nonivamide at doses considered to be therapeutic are generally not considered readily available commercially 1. Subsequently, the pharmacodynamics of nicoboxil are considered useful in commercially available combination products largely because they combine with those of nonivamide to offer a synergistic effect from the unique complementary actions of these two agents 5.
Subsequently, nonivamide is a synthetic capsaicin analog with analgesic properties which are assumed to result from the depletion of Substance P in the peripheral nociceptive C-fibres and A-delta nerve fibers upon repetitive topical application 5. Resultant stimulation of afferent nerve endings in the skin evidently causes a dilatory effect on the surrounding blood vessels accompanied by an intense, long-lasting sensation of warmth associated with the nonivamide use 5.
Given the proposed effect of nonivamide, it is believed that nicoboxil is a vitamin of the B complex 6 that possesses vasodilating properties facilitated by prostaglandin 5. The observed hyperaemic increased blood flow effect of nicoboxil occurs earlier and is described as being more intense than the nonivamide hyperaemic effect 5. Nicoboxil and nonivamide are consequently generally indicated as a combination product because the pharmacodynamics of nicoboxil are considered useful as a complement to those of nonivamide, and vice versa 5,1. In essence, both compounds induce vasodilation by different effects and therefore have complementary abilities inducing increased blood flow, thus hastening the hyperaemic skin reaction 7.
- Mechanism of action
In particular, nicoboxil is considered a rubefacient 5,1. However, the specific mechanism of action by which rubefacients like nicoboxil elicit pharmacologic effects has not yet been formally elucidated 3,4. Nevertheless, it is generally proposed that rubefacients cause irritation of the skin when applied topically, and are believed to alleviate pain in muscles, joints, tendons, and other musculoskeletal pains in the extremities by counter-irritation 3. This specific term, 'counter-irritant', derives from the fact that rubefacients can cause a reddening of the skin by causing the blood vessels of the skin to dilate, which gives a soothing feeling of warmth 3. In essence, the term largely refers to the notion that irritation of the sensory nerve endings alters or offsets pain in the underlying muscle or joints that are innervated by the same nerves 3.
In fact, the vasodilation effect of rubefacients like nicoboxil has been considered the result of nerve conduction mechanisms as early as the late 1950s when certain studies demonstrated that the concomitant application of xylocaine could counteract or prevent the vasolidator response to rubefacients in 50% of such related experiments 4.
Specific investigations on absorption of dermally applied nicoboxil in laboratory animals or target species were not available 6. Published data for nicotinate esters related to nicoboxil indicated however, that members of this class of compounds are in principle able to penetrate skin .
Regardless, there is interest in the studies that demonstrate nicoboxil and nonivamide combination topical applications as effective and safe analgesic products precisely because such topical formulations are expected to have much lower systemic absorption - and thus less exposure to systemic side effects (ie. like gastrointestinal upset, drowsiness, etc.) - than the oral non-steroidal anti-inflammatory drugs, opioids, muscle relaxants, and steroids that may be more commonly prescribed over a rubefacient like nicoboxil 1,2.
Nevertheless, despite the fact that topical nicoboxil and nonivamide products been available to use in some parts of Europe since the 1950s to treat discomfort of the muscuoskeletal system, the effects of nicoboxil and nonivamide have not been investigated in detail and a lack of detailed studies on nicoboxil pharmacodynamics and pharmacokinetics remains ongoing 1.
- Volume of distribution
Despite the fact that topical nicoboxil and nonivamide products been available to use in some parts of Europe since the 1950s to treat discomfort of the muscuoskeletal system, the effects of nicoboxil and nonivamide have not been investigated in detail and a lack of detailed studies on nicoboxil pharmacodynamics and pharmacokinetics remains ongoing 1. Readily accessible data regarding the volume of distribution of nicoboxil is subsequently not available.
- Protein binding
Despite the fact that topical nicoboxil and nonivamide products been available to use in some parts of Europe since the 1950s to treat discomfort of the muscuoskeletal system, the effects of nicoboxil and nonivamide have not been investigated in detail and a lack of detailed studies on nicoboxil pharmacodynamics and pharmacokinetics remains ongoing 1. Readily accessible data regarding the protein binding of nicoboxil is subsequently not available.
Any systemically absorbed nicoboxil is expected to be hydrolyzed to nicotinic acid and 2-butoxyethanol in blood plasma 6. In vitro it is reported that such hydrolysis reactions are catalyzed by esterase-like activity of serum albumin and by plasma esterases 6. The nicotinic acid metabolite is also capable of vascular dilatation 6. In humans, the urinary elimination of 2-butoxyethanol's metabolite, 2-butoxyacetic acid was also reported 6.
The metabolism of nicoboxil is considered to be rapid 6.
Hover over products below to view reaction partners
- Route of elimination
Following ester cleavage, the nicotinic acid metabolite is expected to enter the endogenous metabolic pool as a part of the vitamin B complex 6. The 2-butoxyethanol metabolite is believed to be mainly excreted primarily in the urine and to a certain extent, in exhaled air 6. In humans, the urinary elimination of 2-butoxyethanol's metabolite, 2-butoxyacetic acid was also reported 6.
The half-life of ester hydrolysis was found to be very short in the presence of human serum albumin - less than 15 minutes, 50uM 6.
The elimination of nicoboxil is considered to be rapid 6.
Despite the fact that topical nicoboxil and nonivamide products been available to use in some parts of Europe since the 1950s to treat discomfort of the muscuoskeletal system, the effects of nicoboxil and nonivamide have not been investigated in detail and a lack of detailed studies on nicoboxil pharmacodynamics and pharmacokinetics remains ongoing 1. Readily accessible data regarding the clearance of nicoboxil is subsequently 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.
Nicoboxil is of low acute toxicity 6. No adverse side effects were reported in humans after therapeutic use of the combination of nicoboxil/nonivamide 6. In a study using dermal application of nicoboxil/nonivamide in over 1000 patients, no allergic reactions were observed 6.
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
- 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.
Drug Interaction Tenofovir alafenamide The serum concentration of Tenofovir alafenamide can be increased when it is combined with Nicoboxil.Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more
- Food Interactions
- No interactions found.
- 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.
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Actinac Pwr Nicoboxil (24 mg / g) + Allantoin (24 mg / g) + Chloramphenicol (40 mg / g) + Hydrocortisone acetate (40 mg / g) + Octasulfur (320 mg / g) Powder Topical Roussel Canada Inc. 1978-12-31 1996-09-09 Actinac Pws Nicoboxil (24 mg / g) + Allantoin (24 mg / g) + Chloramphenicol (40 mg / g) + Hydrocortisone acetate (40 mg / g) + Octasulfur (320 mg / g) Powder, for solution Topical Hoechst Roussel Canada Inc. 1994-12-31 2001-07-20 Finalgon - Salbe Nicoboxil (25 mg) + Nonivamide (4 mg) Ointment Topical Zentiva K.S. 1953-12-07 Not applicable Nonivamid + Nicoboxil Zentiva 4 mg/g + 25 mg/g Salbe Nicoboxil (25 mg/g) + Nonivamide (4 mg/g) Ointment Cutaneous Zentiva 2018-04-17 Not applicable
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- This compound belongs to the class of organic compounds known as pyridinecarboxylic acids. These are compounds containing a pyridine ring bearing a carboxylic acid group.
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Pyridines and derivatives
- Sub Class
- Pyridinecarboxylic acids and derivatives
- Direct Parent
- Pyridinecarboxylic acids
- Alternative Parents
- Heteroaromatic compounds / Carboxylic acid esters / Monocarboxylic acids and derivatives / Dialkyl ethers / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives
- Aromatic heteromonocyclic compound / Azacycle / Carboxylic acid derivative / Carboxylic acid ester / Dialkyl ether / Ether / Heteroaromatic compound / Hydrocarbon derivative / Monocarboxylic acid or derivatives / Organic nitrogen compound
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- pyridines, aromatic carboxylic acid (CHEBI:32322)
- Affected organisms
- Humans and other mammals
- CAS number
- InChI Key
- IUPAC Name
- 2-butoxyethyl pyridine-3-carboxylate
- General References
- Gaubitz M, Schiffer T, Holm C, Richter E, Pisternick-Ruf W, Weiser T: Efficacy and safety of nicoboxil/nonivamide ointment for the treatment of acute pain in the low back - A randomized, controlled trial. Eur J Pain. 2016 Feb;20(2):263-73. doi: 10.1002/ejp.719. Epub 2015 Apr 30. [Article]
- Blahova Z, Holm JC, Weiser T, Richter E, Trampisch M, Akarachkova E: Nicoboxil/nonivamide cream effectively and safely reduces acute nonspecific low back pain - a randomized, placebo-controlled trial. J Pain Res. 2016 Dec 14;9:1221-1230. doi: 10.2147/JPR.S118329. eCollection 2016. [Article]
- Matthews P, Derry S, Moore RA, McQuay HJ: Topical rubefacients for acute and chronic pain in adults. Cochrane Database Syst Rev. 2009 Jul 8;(3):CD007403. doi: 10.1002/14651858.CD007403.pub2. [Article]
- FULTON GP, FARBER EM, MORECI AP: The mechanism of action of rubefacients. J Invest Dermatol. 1959 Dec;33:317-25. [Article]
- Finalgon Cream (nonivamide and butoxyethyl nicotinate) Label [File]
- European Agency for the Evaluation of Medicinal Products Veterinary Medicines Evaluation Unit: Committee for Veterinary Medicinal Products Nicoboxil Summary Report [File]
- Bundesinstitut fur Arzneimittel und Medizinprodukte Decentralised Procedure Public Assessment Report: Finalgon 4 mg/g + 25 mg/g Salbe Nonivamide, Nicoboxil [File]
- Download (34.7 KB)
- Clinical Trials
Phase Status Purpose Conditions Count 3 Completed Treatment Acute Low Back Pain 1 3 Completed Treatment Back Pain Lower Back 1
- Not Available
- Not Available
- Dosage Forms
Form Route Strength Powder Topical Powder, for solution Topical Ointment Topical Ointment Cutaneous
- Not Available
- Not Available
- Not Available
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 6.1 mg/mL ALOGPS logP 1.99 ALOGPS logP 2.04 Chemaxon logS -1.6 ALOGPS pKa (Strongest Basic) 3.24 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 48.42 Å2 Chemaxon Rotatable Bond Count 8 Chemaxon Refractivity 60.84 m3·mol-1 Chemaxon Polarizability 25.03 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
- Mass Spec (NIST)
- Not Available
Spectrum Spectrum Type Splash Key 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
Drug created at October 21, 2016 01:12 / Updated at June 12, 2021 10:54