| Targets |
(S)-Linalool interacts with several molecular targets. It acts as a positive modulator of GABAA receptors (specifically the alpha1beta2gamma2 subtype), contributing to its anxiolytic and sedative effects. It also inhibits the NMDA receptor and voltage-gated sodium channels, which may underlie its analgesic and anticonvulsant activities. Additionally, it activates TRPA1 and TRPV1 channels, leading to anti-inflammatory and local analgesic effects. It also has antioxidant properties by scavenging reactive oxygen species.
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| ln Vitro |
In vitro, (S)-linalool (10-500 uM) inhibits nitric oxide (NO) production and reduces pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6) in LPS-stimulated macrophages. It protects neuronal cells against glutamate-induced excitotoxicity and oxidative stress by reducing calcium influx and ROS levels. It also suppresses the proliferation of certain cancer cell lines (e.g., breast cancer MCF-7, colon cancer HCT116) with IC50 values of 100-300 uM. It enhances GABAA receptor-mediated chloride currents in patch-clamp recordings. It is non-cytotoxic to normal cells at concentrations up to 500 uM.
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| ln Vivo |
In vivo, (S)-linalool exhibits anxiolytic effects in rodent behavioral tests (elevated plus maze, open field) at oral doses of 25-100 mg/kg. It also reduces pain in formalin-induced nociception and chronic constriction injury models. It has anti-inflammatory activity in carrageenan-induced paw edema (ED50 ~50 mg/kg). Inhalation of (S)-linalool vapors (0.5-2%) reduces stress and improves sleep quality in mice. It also shows neuroprotective effects in models of cerebral ischemia and Alzheimer's disease. It is rapidly metabolized and does not cause significant toxicity at therapeutic doses.
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| Enzyme Assay |
For GABAA receptor binding assays, rat brain cortical membranes are prepared. (S)-Linalool (0.1-1000 uM) is incubated with [3H]flunitrazepam (1 nM) in 50 mM Tris-citrate buffer (pH 7.4) at 4degC for 60 minutes. Non-specific binding is determined with 10 uM diazepam. Samples are filtered and counted. For chloride flux assays, CHO cells expressing alpha1beta2gamma2 GABAA receptors are loaded with a fluorescent chloride indicator (MEQ) and treated with linalool; fluorescence changes are recorded. For TRP channel assays, HEK293 cells expressing TRPA1 or TRPV1 are used in calcium imaging.
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| Cell Assay |
For anti-inflammatory assays, RAW264.7 macrophages are cultured in DMEM with 10% FBS. Cells are pre-treated with (S)-linalool (10-500 uM) for 1 hour, then stimulated with LPS (1 ug/mL) for 24 hours. NO is measured by Griess reagent. TNF-alpha and IL-6 are measured by ELISA. Cell viability is assessed by MTT. For neuroprotection, SH-SY5Y cells are treated with linalool (10-200 uM) for 1 hour, then exposed to 1 mM glutamate for 24 hours; cell viability is measured, and ROS is detected by DCFH-DA. For anti-proliferation, cancer cells are treated for 48 hours, and MTT assay is performed.
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| Animal Protocol |
For anxiety studies, male Swiss mice (25-30 g) are administered (S)-linalool orally (25-100 mg/kg) or intraperitoneally (10-50 mg/kg) in saline with 0.5% Tween 80. After 30-60 minutes, mice are placed in an elevated plus maze (EPM): the time spent in open arms and number of entries are recorded for 5 minutes. Diazepam (2 mg/kg) is used as a positive control. For pain studies, formalin (2.5%, 20 uL) is injected into the hind paw, and licking time is measured in two phases (0-5 min and 15-30 min). For inflammation, carrageenan (1%) is injected into the paw, and paw volume is measured by plethysmometer at 1-4 hours.
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| ADME/Pharmacokinetics |
(S)-Linalool is lipophilic (logP ~2.8) and is rapidly absorbed after oral administration. In rats, oral bioavailability is approximately 30-50% due to first-pass metabolism. After oral dosing (50-100 mg/kg), Tmax is 0.5-1.5 hours, and Cmax is 1-5 ug/mL. It is extensively metabolized in the liver by CYP450 enzymes (CYP2B6, CYP2C19, CYP3A4) to hydroxylated metabolites (e.g., 8-hydroxylinalool) and their glucuronides. The elimination half-life is 1-2 hours. It is excreted in urine. Linalool does not accumulate in tissues. Inhalation leads to rapid absorption through the lungs.
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| Toxicity/Toxicokinetics |
(S)-Linalool has low acute toxicity. The oral LD50 in rats is >2000 mg/kg. It is not a skin irritant but may cause mild eye irritation. It is not mutagenic in Ames tests. In a 90-day feeding study in rats, no adverse effects were observed at doses up to 500 mg/kg/day. It is not classified as a carcinogen. However, high concentrations ( >1000 mg/kg) may cause ataxia and sedation due to CNS depression. The compound is considered safe for use as a flavor and fragrance ingredient (GRAS, FEMA No. 2635).
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| References | |
| Additional Infomation |
(S)-Linalool is a widely used natural fragrance and flavoring agent. It is found in over 200 essential oils, including lavender, bergamot, and coriander. It has been studied for its anxiolytic, analgesic, anti-inflammatory, and neuroprotective properties. It is not approved as a drug but is used in aromatherapy and traditional medicine. The (S)-enantiomer may have different biological activity compared to the (R)-enantiomer, with (S)-linalool often reported to have higher GABAA receptor affinity. It is a research compound for studying CNS and inflammatory disorders.
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| Exact Mass |
154.136
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|---|---|
| CAS # |
126-90-9
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| PubChem CID |
67179
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| Appearance |
Liquid
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| Hydrogen Bond Donor Count |
1
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
11
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| Complexity |
154
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| Defined Atom Stereocenter Count |
1
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| InChi Key |
CDOSHBSSFJOMGT-SNVBAGLBSA-N
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| InChi Code |
InChI=1S/C10H18O/c1-5-10(4,11)8-6-7-9(2)3/h5,7,11H,1,6,8H2,2-4H3/t10-/m1/s1
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| Chemical Name |
(3S)-3,7-dimethylocta-1,6-dien-3-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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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) |
DMSO : ~200 mg/mL (~1296.60 mM; with sonication)
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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.) |
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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