Identification
- Summary
Methyl nicotinate is a methyl ester of niacin used to treat muscle and joint pain.
- Generic Name
- Methyl nicotinate
- DrugBank Accession Number
- DB13882
- Background
Methyl nicotinate is the methyl ester of Niacin that is used as an active ingredient as a rubefacient in over-the-counter topical preparations indicated for muscle and joint pain. The action of methyl nicotinate as a rubefacient is thought to involve peripheral vasodilation. For veterinary purposes, methyl nicotinate is used to treat respiratory diseases, vascular disorders, rheumatoid arthritis, and muscle and joint pains 4.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Methyl nicotinate (DB13882)
- Weight
- Average: 137.136
Monoisotopic: 137.047678473 - Chemical Formula
- C7H7NO2
- Synonyms
- 3-(Carbomethoxy)pyridine
- 3-(Methoxycarbonyl)pyridine
- 3-pyridinecarboxylic acid methyl ester
- Heat spray
- Methyl 3-pyridinecarboxylate
- Methyl nicotinate
- Methyl-nicotinate
- Methylnicotinate
- Nicotinic acid, methyl ester
Pharmacology
- Indication
Indicated for the temporary relief of aches and pains in muscles, tendons, and joints.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Symptomatic treatment of Generalized joint pain ••• ••••• Symptomatic treatment of Localized muscle pain ••• ••••• Symptomatic treatment of Muscle ache ••• ••••• - Contraindications & Blackbox Warnings
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Following topical administration, methyl nicotinate acts as a peripheral vasodilator to enhance local blood flow at the site of application. It induced vasodilation of the peripheral blood capillaries which are located in the dermal papillae of upper dermis layers adjacent to the epidermis–dermis junction 1. During tissue penetration at the dermis, methyl nicotinate is hydrolyzed to nicotinic acid 1. In human volunteers, topical administration of methyl nicotinate caused vasodilation-induced generalized cutaneous erythema 1.
- Mechanism of action
While the mechanism of action of methyl nicotinate and other topically-administered nicotinic acid esters is not clear, it is thought that methyl nicotinate promotes the release of prostaglandin D2 that is strictly locally-acting due to its short half-life 1. It was demonstrated in human subjects that the local cutaneous vascular response to methyl nicotinic was suppressed by inhibitors of prostaglandin biosynthesis, indicating that the effect of methyl nicotinate on vascular smooth muscles may be mediated by the release of local prostaglandins 5. Prostaglandins released from the skin and blood vessels induce cutaneous vasodilation 5.
- Absorption
The presence of methyl group facilitates the penetration of methyl nicotinate through the skin with good lipophilicity, allowing rapid absorption following topical administration 4. In vitro, about 80-90% of the polar compounds methyl nicotinate rapidly penetrated the skin 4. It was demonstrated in excised skin of hairless mice that methyl nicotinate can effectively bypass the stratum corneum layer of the skin 4. In humans, nicotinic acid and nicotinamide were shown to be rapidly absorbed from the stomach and intestine via a sodium carrier-mediated mechanism at low concentrations 4.
- Volume of distribution
According to the animal studies, nicotinic acid is mainly concentrated in the liver, kidneys, and adipose tissue 4.
- Protein binding
No pharmacokinetic data available.
- Metabolism
Methyl nicotinate undergoes ester hydrolysis to form nicotinic acid and methanol 4. The hydrolysis is thought to be mediated by nonspecific α-naphthylacetate-esterase at the dermis layer of the skin 1.
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- Route of elimination
Following epicutaneous administration of small radiolabelled dose of methyl nicotinate in human volunteers, approximately 15% of the dose was recovered in the urine within 108 hours after treatment 3. The excretion of nicotinic acid mainly takes place in the kidneys 3.
- Half-life
In vitro, the half-life of methyl nicotinate in the dermis was 3 to 10 minutes 2.
- Clearance
No pharmacokinetic data available.
- Adverse Effects
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The acute subcutaneous LD50 of structurally-related nicotinamide and nicotinic acid in rats were 1.68 and 5.0 g/kg bw, respectively 3. In humans, oral ingestion of 3-9 g of nicotinic acid per day resulted in "niacin hepatitis", gout, and impaired glucose intolerance within a short period of time 3.
- 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
- 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.- Active Moieties
Name Kind UNII CAS InChI Key Niacin unknown 2679MF687A 59-67-6 PVNIIMVLHYAWGP-UHFFFAOYSA-N - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Arth Arrest Methyl nicotinate (0.5 g/100g) + Capsaicin (0.025 g/100g) Cream Topical Key 2 Health, Inc. 2011-02-11 Not applicable US 
Arth RX Topical Analgesic Methyl nicotinate (0.5 g/100g) + Capsaicin (0.025 g/100g) Lotion Topical Hcd Sales 2011-02-12 Not applicable US Arthricare for Women Multi-action Methyl nicotinate (0.25 %) + Capsaicin (0.025 %) + Levomenthol (1.25 %) Cream Topical Del Pharmaceuticals Inc. 1991-12-31 2005-06-20 Canada 
Arthricare for Women Nighttime Methyl nicotinate (0.25 %) + Levomenthol (1.25 %) + Methyl salicylate (30 %) Cream Topical Del Pharmaceuticals Inc. 1998-07-01 2003-07-21 Canada Arthricare Pain Relieving Rub Triple Medicated Gel Methyl nicotinate (0.7 %) + Levomenthol (1.25 %) + Methyl salicylate (30 %) Gel Topical Del Pharmaceuticals Inc. 1991-12-31 1999-08-05 Canada
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- 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.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Pyridines and derivatives
- Sub Class
- Pyridinecarboxylic acids and derivatives
- Direct Parent
- Pyridinecarboxylic acids
- Alternative Parents
- Methyl esters / Heteroaromatic compounds / Monocarboxylic acids and derivatives / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives
- Substituents
- Aromatic heteromonocyclic compound / Azacycle / Carboxylic acid derivative / Carboxylic acid ester / Heteroaromatic compound / Hydrocarbon derivative / Methyl ester / Monocarboxylic acid or derivatives / Organic nitrogen compound / Organic oxide
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 7B1AVU9DJN
- CAS number
- 93-60-7
- InChI Key
- YNBADRVTZLEFNH-UHFFFAOYSA-N
- InChI
- InChI=1S/C7H7NO2/c1-10-7(9)6-3-2-4-8-5-6/h2-5H,1H3
- IUPAC Name
- methyl pyridine-3-carboxylate
- SMILES
- COC(=O)C1=CN=CC=C1
References
- General References
- Muller B, Kasper M, Surber C, Imanidis G: Permeation, metabolism and site of action concentration of nicotinic acid derivatives in human skin. Correlation with topical pharmacological effect. Eur J Pharm Sci. 2003 Oct;20(2):181-95. [Article]
- Roskos KV, Bircher AJ, Maibach HI, Guy RH: Pharmacodynamic measurements of methyl nicotinate percutaneous absorption: the effect of aging on microcirculation. Br J Dermatol. 1990 Feb;122(2):165-71. [Article]
- The European Agency Committee for Veterinary Medicinal Products: Methyl Nicotinate Summary Report [File]
- Norwegian Food Safety Authority (Mattilsynet): Methyl Nicotinate (MN) Risk Profile [File]
- Prostaglandins and nicotine-provoked increase in cutaneous blood flow [File]
- External Links
- Human Metabolome Database
- HMDB0029806
- PubChem Compound
- 7151
- PubChem Substance
- 347829331
- ChemSpider
- 21111785
- 29900
- ChEBI
- 134761
- ChEMBL
- CHEMBL379845
- ZINC
- ZINC000000001706
- MSDS
- Download (38.2 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 2, 3 Completed Diagnostic Schizophrenia 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Gel Topical Cream Topical Lotion Topical Aerosol, spray Topical Ointment Topical Patch Topical Aerosol Topical - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 38-43 MSDS boiling point (°C) 209 MSDS water solubility Soluble Norwegian Food Safety Authority Methyl Nicotinate (MN) Risk Profile logP 0.8 Norwegian Food Safety Authority Methyl Nicotinate (MN) Risk Profile - Predicted Properties
Property Value Source Water Solubility 193.0 mg/mL ALOGPS logP 0.45 ALOGPS logP 0.76 Chemaxon logS 0.15 ALOGPS pKa (Strongest Basic) 3.24 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 39.19 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 35.93 m3·mol-1 Chemaxon Polarizability 13.23 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule Yes 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]- 127.346612 predictedDarkChem Lite v0.1.0 [M-H]- 126.913012 predictedDarkChem Lite v0.1.0 [M-H]- 127.683512 predictedDarkChem Lite v0.1.0 [M-H]- 127.212812 predictedDarkChem Lite v0.1.0 [M-H]- 124.40091 predictedDeepCCS 1.0 (2019) [M+H]+ 128.244512 predictedDarkChem Lite v0.1.0 [M+H]+ 128.116512 predictedDarkChem Lite v0.1.0 [M+H]+ 127.965012 predictedDarkChem Lite v0.1.0 [M+H]+ 127.992512 predictedDarkChem Lite v0.1.0 [M+H]+ 128.11902 predictedDeepCCS 1.0 (2019) [M+Na]+ 127.752712 predictedDarkChem Lite v0.1.0 [M+Na]+ 127.702612 predictedDarkChem Lite v0.1.0 [M+Na]+ 127.651612 predictedDarkChem Lite v0.1.0 [M+Na]+ 137.24156 predictedDeepCCS 1.0 (2019)
Drug created at September 06, 2017 19:35 / Updated at February 21, 2021 18:54