| Targets |
(+)-Neoisomenthol has no defined therapeutic target. As a menthol analog, it is a chemical agonist of the transient receptor potential melastatin 8 (TRPM8) channel, also known as the cold and menthol receptor (CMR1). Activation of TRPM8 by neoisomenthol generates a sensation of cooling and has analgesic effects. It also has antibacterial properties, likely due to disruption of the bacterial cell membrane. It may also interact with GABA_A receptors. It does not significantly inhibit COX-1 or COX-2.
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| ln Vitro |
In vitro, (+)-Neoisomenthol exhibits antibacterial activity against oral pathogens, including Streptococcus mutans and Porphyromonas gingivalis. The Minimum Inhibitory Concentration (MIC) for S. mutans is 0.5-1.0 mg/mL. In a TRPM8-expressing HEK293 cell assay, (+)-Neoisomenthol elicits a concentration-dependent increase in intracellular calcium with an EC₅0 of approximately 10-50 uM, similar to menthol. It also exhibits moderate antioxidant activity in DPPH and ABTS radical scavenging assays. It is not cytotoxic to human gingival fibroblasts.
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| ln Vivo |
In vivo, (+)-Neoisomenthol is used as a flavoring agent. It produces a cooling sensation when applied to the skin or oral mucosa due to TRPM8 activation. In animal models, it may exhibit mild analgesic effects in the hot plate test (antinociceptive). It has been shown to inhibit the growth of oral bacteria in a rat model of dental caries when included in toothpaste. It is used as a fragrance ingredient in cosmetics and as a flavoring agent in chewing gum and candy. It has no central nervous system depressant activity at normal doses.
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| Enzyme Assay |
In vitro antibacterial activity (MIC determination): Oral pathogens (S. mutans, P. gingivalis, F. nucleatum) are cultured in BHI or Brucella broth anaerobically. Bacteria are adjusted to 1-5×10⁵ CFU/mL. (+)-Neoisomenthol is dissolved in DMSO and serially diluted in 96-well plates (0.125-8 mg/mL). Plates are incubated at 37degC under anaerobic conditions for 24-48 h. The MIC is the lowest concentration with no visible growth. For TRPM8 activation assay, HEK293 cells stably expressing human TRPM8 are loaded with Fluo-4 AM fluorescent calcium indicator. Various concentrations of (+)-Neoisomenthol (1-1000 uM) are added, and fluorescence (λex 488 nm, λem 520 nm) is measured. The EC₅0 is calculated.
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| Cell Assay |
(+)-Neoisomenthol is not used in standard cell-based assays for drug discovery. For toxicity screening, HepG2 or HEK293 cells are seeded in 96-well plates (1×10⁴ cells/well) and treated with (+)-Neoisomenthol (1-5000 uM) for 24-72 h. Cell viability is measured by MTT assay. The CC₅0 is expected to be >2000 uM, indicating very low cytotoxicity. For anti-inflammatory activity, RAW 264.7 macrophages are pretreated with (+)-Neoisomenthol (50-500 uM) for 1 h, then stimulated with LPS (1 ug/mL). TNF-alpha and IL-6 levels in the supernatant are measured by ELISA. No significant inhibition is observed.
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| Animal Protocol |
For evaluation of oral antimicrobial activity, a rat caries model is used. Specific-pathogen-free (SPF) rats (21 days old, n=20/group) are infected with Streptococcus sobrinus. The rats are fed a high-sucrose diet (Diet 2000). A toothpaste containing 0.5-1% (+)-Neoisomenthol is applied to the teeth daily for 5 weeks. The control group receives placebo toothpaste. At termination, the jaws are removed, and the caries score (Keyes scoring method) is calculated. A reduction in caries score indicates antimicrobial activity. For toxicokinetics, rats are administered (+)-Neoisomenthol orally (100-500 mg/kg), and plasma and urine are collected.
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| ADME/Pharmacokinetics |
(+)-Neoisomenthol is lipophilic (LogP 3.0). It is readily absorbed from the gastrointestinal tract following oral ingestion. It undergoes extensive Phase II metabolism via glucuronidation and sulfation of the hydroxyl group. It may also undergo Phase I oxidation (e.g., hydroxylation of the isopropyl group). The half-life in the body is short (2-4 h). It is excreted in the urine as conjugated metabolites (glucuronides and sulfates). It does not bioaccumulate in tissues. It is generally recognized as safe (GRAS) as a flavoring agent.
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| Toxicity/Toxicokinetics |
For (+)-Neoisomenthol, hazard statements: H315 (Causes skin irritation), H319 (Causes serious eye irritation), H335 (May cause respiratory irritation). Signal word: Warning. Precautionary statements: P261 (Avoid breathing dust/fume/gas/mist/vapors/spray), P280 (Wear protective gloves/protective clothing/eye protection/face protection), P305+P351+P338 (IF IN EYES: Rinse cautiously with water for several minutes). The compound is flammable (flash point 91degC). Storage: at 2-8degC in a tightly sealed container, protected from light.
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| References |
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| Additional Infomation |
(+)-Neoisomenthol ((1R,2R,5R)-2-isopropyl-5-methylcyclohexan-1-ol; CAS# 20752-34-5) is a research-grade flavoring agent and fragrance standard. It is not an FDA-approved drug. It is used as a reference standard for the analysis of monoterpenes in essential oils and as a tool for TRPM8 channel research. For research use only, not for diagnostic or therapeutic applications.
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| Molecular Formula |
C10H20O
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|---|---|
| Molecular Weight |
156.27
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| Exact Mass |
156.151
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| CAS # |
20752-34-5
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| Related CAS # |
(±)-Neoisomenthol
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| PubChem CID |
19244
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| Appearance |
Typically exists as solids at room temperature
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| Melting Point |
100 °F (NTP, 1992)
; -8 °C
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| Hydrogen Bond Donor Count |
1
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
11
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| Complexity |
120
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| Defined Atom Stereocenter Count |
3
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| SMILES |
C[C@@H]1CC[C@@H]([C@@H](C1)O)C(C)C
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| InChi Key |
NOOLISFMXDJSKH-OPRDCNLKSA-N
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| InChi Code |
InChI=1S/C10H20O/c1-7(2)9-5-4-8(3)6-10(9)11/h7-11H,4-6H2,1-3H3/t8-,9-,10-/m1/s1
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| Chemical Name |
(1R,2R,5R)-5-methyl-2-propan-2-ylcyclohexan-1-ol
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 6.3992 mL | 31.9959 mL | 63.9918 mL | |
| 5 mM | 1.2798 mL | 6.3992 mL | 12.7984 mL | |
| 10 mM | 0.6399 mL | 3.1996 mL | 6.3992 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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