Methyl nicotinate

Overview

Description
A medication used to treat muscle and joint pain.
Description
A medication used to treat muscle and joint pain.
DrugBank ID
DB13882
Type
Small Molecule
US Approved
NO
Other Approved
YES
Clinical Trials
Phase 0
0
Phase 1
0
Phase 2
1
Phase 3
1
Phase 4
0
Therapeutic Categories
  • Nicotinic Acids

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
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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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Symptomatic treatment ofGeneralized joint pain••• •••••
Symptomatic treatment ofLocalized muscle pain••• •••••
Symptomatic treatment ofMuscle ache••• •••••
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.

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

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
  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. [Article]
  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. [Article]
  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
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PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
2, 3CompletedDiagnosticSchizophrenia1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
GelTopical
CreamTopical
LotionTopical
Aerosol, sprayTopical
OintmentTopical
PatchTopical
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-MSsplash10-0a4i-2900000000-3915717ccabc67393833
GC-MS Spectrum - EI-BGC-MSsplash10-004i-9400000000-7c3a8027277de3a14a41
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4r-0900000000-220daa4bc44719961c0f
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-000i-0900000000-3d11cdc414527b2f51db
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-1900000000-1af564e8d8e7d9cbde49
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-9300000000-a412e71210b6bf749b7f
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0059-9100000000-2546a78df467352b49a4
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-9000000000-71dc3221e2e78e762230
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-127.346612
predicted
DarkChem Lite v0.1.0
[M-H]-126.913012
predicted
DarkChem Lite v0.1.0
[M-H]-127.683512
predicted
DarkChem Lite v0.1.0
[M-H]-127.212812
predicted
DarkChem Lite v0.1.0
[M-H]-124.40091
predicted
DeepCCS 1.0 (2019)
[M+H]+128.244512
predicted
DarkChem Lite v0.1.0
[M+H]+128.116512
predicted
DarkChem Lite v0.1.0
[M+H]+127.965012
predicted
DarkChem Lite v0.1.0
[M+H]+127.992512
predicted
DarkChem Lite v0.1.0
[M+H]+128.11902
predicted
DeepCCS 1.0 (2019)
[M+Na]+127.752712
predicted
DarkChem Lite v0.1.0
[M+Na]+127.702612
predicted
DarkChem Lite v0.1.0
[M+Na]+127.651612
predicted
DarkChem Lite v0.1.0
[M+Na]+137.24156
predicted
DeepCCS 1.0 (2019)

Drug created at September 06, 2017 19:35 / Updated at February 21, 2021 18:54