Methyl nicotinate

Identification

Name
Methyl nicotinate
Accession Number
DB13882
Description

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
Thumb
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.

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

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.

Hover over products below to view reaction partners

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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Toxicity

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.

Affected organisms
Not Available
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

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Active Moieties
NameKindUNIICASInChI Key
Niacinunknown2679MF687A59-67-6PVNIIMVLHYAWGP-UHFFFAOYSA-N
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Arth ArrestMethyl nicotinate (0.5 g/100g) + Capsaicin (0.025 g/100g)CreamTopicalKey 2 Health, Inc.2011-02-11Not applicableUS flag
Arth RX Topical AnalgesicMethyl nicotinate (0.5 g/100g) + Capsaicin (0.025 g/100g)LotionTopicalHcd Sales2011-02-12Not applicableUS flag
Arthricare for Women Multi-actionMethyl nicotinate (0.25 %) + Capsaicin (0.025 %) + Levomenthol (1.25 %)CreamTopicalDel Pharmaceuticals Inc.1991-12-312005-06-20Canada flag
Arthricare for Women NighttimeMethyl nicotinate (0.25 %) + Levomenthol (1.25 %) + Methyl salicylate (30 %)CreamTopicalDel Pharmaceuticals Inc.1998-07-012003-07-21Canada flag
Arthricare Pain Relieving Rub Triple Medicated GelMethyl nicotinate (0.7 %) + Levomenthol (1.25 %) + Methyl salicylate (30 %)GelTopicalDel Pharmaceuticals Inc.1991-12-311999-08-05Canada flag
BiobalsamMethyl nicotinate (0.75 %) + Capsicum oleoresin (0.05 %)CreamTopicalBiopharmatech Inc.1997-06-111999-07-07Canada flag
Decontractyl BaumeMethyl nicotinate (1 %) + Mephenesin (10 %)OintmentTopicalRobert and Carriere Lab1962-12-311998-07-22Canada flag
MidalganMethyl nicotinate (1 g) + Capsicum (100 mg) + Glycol salicylate (10 g) + Histamine dihydrochloride (100 mg)OintmentTopicalWelcker Lyster Ltd., Division Of Technilab Inc.1948-12-311999-09-17Canada flag
Moor Balm - CrmMethyl nicotinate (.563 %) + Capsaicin (.0563 %)CreamTopicalGolden Moor1996-12-121999-06-21Canada flag
Ultraplast Analgesic SprayMethyl nicotinate (1.6 %) + Ethyl salicylate (4.8 %) + Glycol salicylate (4.8 %) + Methyl salicylate (.96 %)AerosolTopicalWallace, Cameron and Company Ltd.1985-12-312000-07-31Canada flag

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

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
  1. 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. [PubMed:14550884]
  2. 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. [PubMed:2317445]
  3. The European Agency Committee for Veterinary Medicinal Products: Methyl Nicotinate Summary Report [File]
  4. Norwegian Food Safety Authority (Mattilsynet): Methyl Nicotinate (MN) Risk Profile [File]
  5. Prostaglandins and nicotine-provoked increase in cutaneous blood flow [File]
Human Metabolome Database
HMDB0029806
PubChem Compound
7151
PubChem Substance
347829331
ChemSpider
21111785
RxNav
29900
ChEBI
134761
ChEMBL
CHEMBL379845
ZINC
ZINC000000001706
MSDS
Download (38.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2, 3CompletedDiagnosticSchizophrenia1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
CreamTopical
LotionTopical
GelTopical
Aerosol, sprayTopical5 % w/w
OintmentTopical
AerosolTopical
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)38-43MSDS
boiling point (°C)209MSDS
water solubilitySolubleNorwegian Food Safety Authority Methyl Nicotinate (MN) Risk Profile
logP0.8Norwegian Food Safety Authority Methyl Nicotinate (MN) Risk Profile
Predicted Properties
PropertyValueSource
Water Solubility193.0 mg/mLALOGPS
logP0.45ALOGPS
logP0.76ChemAxon
logS0.15ALOGPS
pKa (Strongest Basic)3.24ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area39.19 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity35.93 m3·mol-1ChemAxon
Polarizability13.23 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
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
GC-MS Spectrum - EI-BGC-MSsplash10-004i-9400000000-7c3a8027277de3a14a41
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-000i-0900000000-32eb9e18a26af57d26c5
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-000i-0900000000-5685ba3190b1d8797adb
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0zfr-9600000000-22a2e3fff8ba9d56edc0
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-000i-0900000000-e85db02b4f474d26b636
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-000i-0900000000-d9503a788323d33eecd9
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0zfr-9600000000-c54c379ee39a53af4ff8

Drug created on September 06, 2017 13:35 / Updated on June 12, 2020 10:53

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