At sub-anesthetic doses, 1-Octanol suppresses native T currents with an IC50 of about 4 μM. By contrast, the inhibitory effect of 1-octanol on recombinant CaV3.3 T channels that were heterologously produced in human embryonic kidney cells was 30 times lower [1].

Absorption, Distribution and Excretion
The reported in vitro dermal flux in human skin (epidermis) is 0.008 mg/cm²/hr, indicating low permeability. Metabolism/Metabolites Primary fatty alcohols undergo two main reactions in vivo: oxidation to carboxylic acids and direct conjugation with glucuronic acid. The first reaction produces an intermediate aldehyde, from which the carboxylic acid may be completely oxidized to carbon dioxide, excreted as carbon dioxide, or conjugated with glucuronic acid to form ester glucuronides. The extent to which alcohols undergo the second reaction (i.e., direct conjugation with ether glucuronides) appears to depend on the rate of the first reaction. Rapidly oxidized alcohols rarely form ether glucuronides unless administered in high doses. Urinary metabolites following gavage administration of n-octane to Fischer 344 rats included 2-octanol, 3-octanol, 5-oxohexanoic acid, and 6-oxohepanoic acid. Animal sex affects the relative content of metabolites. Analysis was performed using gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS). This is the first report of keto acids in hydrocarbon oxidative metabolism. Although the 2,2,4-trimethylpentane (isooctane) isomer causes kidney damage in male rats, administration of n-octane did not result in kidney damage. /n-Octane/

Toxicity Summary
Identification and Uses: 1-Octanol is a colorless liquid used for determining partition coefficients, in fragrances, cosmetics, organic synthesis, the production of high-boiling-point ester solvents, as an antifoaming agent, and flavoring agent. 1-Octanol is registered as a pesticide in the United States, but its approved pesticide uses may change periodically; therefore, it is essential to consult federal, state, and local authorities for currently approved uses. It has been used as an experimental drug to treat tremors in patients. Human Exposure and Toxicity: In human patch tests, 1-Octanol in a 2% petrolatum solution did not irritate or sensitize the skin. Octanol may cause transient corneal epithelial damage, which recovers within 48 hours. Common symptoms of 1-Octanol exposure include central nervous system symptoms: headache, muscle weakness, dizziness, ataxia, confusion, delirium, and coma. Gastrointestinal Reactions: Nausea, vomiting, and diarrhea (with an alcoholic odor in the excrement). Inhalation of vapors or the liquid may irritate the skin, eyes, and throat, and may be accompanied by coughing and difficulty breathing. The pungent odor of 1-octanol may mask sensory stimuli and impair the concentration of subjects highly sensitive to chemicals to complete challenging tasks. Animal studies: 1-octanol is mildly irritating to the skin of rabbits and is considered an eye irritant according to EU standards. n-Octanol (0.55 g/kg) induced the greatest decrease in body temperature. In a lung adenoma study, mice were intraperitoneally injected three times weekly with 100 and 500 mg/kg of 1-octanol for 8 weeks without tumor development. Studies have shown that T-type calcium channels (T channels) in the thalamus are cellular targets of general anesthetics. This study recorded T-type currents and their potential low-threshold calcium spikes in neurons of the thalamic reticular nucleus (nRT) in brain slices of young mice and explored the mechanism by which the anesthetic alcohol 1-octanol modulates them. 1-Octanol inhibited native T-type currents at subanesthetic concentrations, with an IC50 of approximately 4 μM. Inhibition of both native and recombinant T-type currents was accompanied by a hyperpolarization shift leading to steady-state inactivation, indicating that 1-octanol stabilized the inactivation state of the channels. In developmental studies in rats, no treatment-related effects were observed in pregnant female rats, including embryo resorption rate, fetal weight, or skeletal/visceral malformations. At concentrations ranging from 4 to 2500 μg/plate (with or without metabolic activation), 1-octanol showed negative results in the Ames Salmonella assay against Ta 98, TA 100, TA 1535, TA 1537, and TA 1538 strains.

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Toxicity Data
LCLo (rat) = 5,600 mg/m³/4h

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Interactions
…The study investigated whether 1-octanol (OCT) could inhibit the toxicity of ethanol (ETOH) to cultured intact mouse embryos. Embryos (3 to 5 segments) were cultured for 6 hours in both alcohol-containing and alcohol-free media, then transferred to control media for an additional 20 hours. Somnolence counts were performed after 26 hours of in vitro culture… 3 μM OCT treatment did not cause delayed embryonic development, while 10 μM and 50 μM OCT gradually increased toxicity. Embryos cultured in 100 mM ETOH for 6 hours showed significantly delayed in vitro development compared to control embryos (19.6 ± 0.6 somnol pairs, n = 5) (13.8 ± 0.7 somnol pairs after 26 hours, n = 15). Co-incubation with 3 μM OCT significantly reduced the toxicity of 100 mM ETOH (16.9 ± 0.6 somnol pairs; n = 23, p < 0.002). All control embryos and 60.9% of embryos in the ethanol/octanol treatment group had ≥17 somnol pairs; in contrast, only 13.4% of embryos in the ethanol-treated group had ≥17 somnol pairs. Conversely, 33.3% of embryos in the ethanol-treated group had ≤12 somites, compared to none in the control group, and only 4.3% in the ethanol/octanol-treated group had ≤12 somites.

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Non-human toxicity values
Rats oral LD50 >5 g/kg
Mice oral LD50 1,800 mg/kg
Rabbit skin LD50 >5 g/kg
Mice intravenous LD50 69 mg/kg
Guinea pig skin LD50 >500 mg/kg

[1]. Mechanisms of inhibition of T-type calcium current in the reticular thalamic neurons by 1-octanol: implication of the protein kinase C pathway. Mol Pharmacol. 2010 Jan;77(1):87-94.

[2]. Microbial production of 1-octanol: A naturally excreted biofuel with diesel-like properties. Metab Eng Commun. 2014 Nov 13;2:1-5.

Octyl alcohol is a clear, colorless liquid with a pungent, aromatic odor. It is insoluble in water and floats on water. Its vapor is heavier than air. The vapor can irritate the eyes, nose, and respiratory system. Oct-1-ol is an octanol with a hydroxyl group at the 1-position. It is a plant metabolite, antifungal agent, pheromone, fuel additive, and bacterial metabolite. It is an octanol and a primary alcohol. Octyl alcohol has been used in trials investigating the treatment of essential tremor. 1-Octanol has been reported in Senegalia berlandieri, Alpinia latilabris, and several other organisms with relevant data. Oct-1-ol is a metabolite found or produced in Saccharomyces cerevisiae. A colorless, slightly viscous liquid, it can be used as an antifoaming agent or wetting agent. It is also used as a solvent for protective coatings, waxes, and oils, and as a raw material for plasticizers. (Excerpted from McGraw-Hill Dictionary of Scientific and Technical Terminology, 5th Edition)
See also: C6-12 alcohols (note moved to); C8-18 and C18 unsaturated alcohols (note moved to).

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Mechanism of Action
This study investigated the effects of various alkanols on the central nervous system using a rat brain synaptosome membrane as an in vitro model. The activity and membrane fluidity of (Ca2+/Mg2+)ATPase were measured. The molar inhibitory effect of n-alkanols on ATPase activity increased with increasing carbon chain length, up to 1-octanol. The effects of 1-octanol and 1-decanol on ATPase activity were biphasic, depending on the alkanol concentration; while 1-dodecylol stimulated ATPase activity. All alkanols studied resulted in increased membrane fluidity… These results suggest that the effect of alkanols on ATPase activity depends on changes in the boundary layer between the membrane and the surrounding medium, as well as the binding of alkanols to enzyme molecules… The bidirectional effects of 1-octanol and 1-decanol, and the stimulatory effect of 1-dodecylol, indicate that more mechanisms are involved… Changes in membrane fluidity do not appear to be a necessary condition for ATPase inhibition. … Studies have shown that T-type calcium channels (T channels) in the thalamus are cellular targets of general anesthetics. This study recorded T-type currents and their associated low-threshold calcium spikes in thalamic reticular nucleus (nRT) neurons in brain slices from young rats and explored the mechanism by which the anesthetic alcohol 1-octanol regulates them. We found that subanesthetic concentrations of 1-octanol inhibited native T-type currents, with an IC50 of approximately 4 μM. In contrast, 1-octanol showed an inhibitory potency of up to 30-fold less on recombinant Ca(V)3.3 T-type channels heterologously expressed in human embryonic kidney cells. Inhibition of both native and recombinant T-type currents was accompanied by a hyperpolarization shift leading to steady-state inactivation, indicating that 1-octanol stabilized the inactivated state of the channels. To investigate the mechanism by which 1-octanol inhibits native nRT T currents, we tested the effects of the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) and PKC inhibitors. We found that PMA slightly increased T currents, while the inactive PMA analog 4α-PMA had no effect on T currents in nRT neurons. Conversely, the calcium-dependent PKC inhibitor 12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole (Go 6976) reduced the baseline T current amplitude in nRT cells and eliminated the effect of subsequently applied 1-octanol. The effect of 1-octanol was also eliminated by the chelation of intracellular calcium ions by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid. In summary, these results suggest that inhibition of calcium-dependent protein kinase C (PKC) signaling may be the molecular basis for 1-octanol's regulation of T-channels in nRT neurons.

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Therapeutic Use
MeSH Title: Pharmacological Action: Solvent
EXPL THER 1-Octanol (an octane alcohol currently used as a food flavoring agent) is known to inhibit tremor at doses far lower than ethanol in animal models of essential tremor (ET). This study conducted a preliminary, randomized, placebo-controlled trial in 12 ET patients with a single oral dose of 1 mg/kg of 1-octanol. No significant side effects or signs of toxicity were observed. 1-Octanol significantly reduced tremor amplitude, with the effect lasting up to 90 minutes. These results indicate that 1-octanol is a well-tolerated and safe potential treatment for ET.

C₈H₁₈O

130.23

130.136

111-87-5

1-Octanol-d17;153336-13-1;1-Octanol-d2;78510-02-8

957

Colorless to light yellow liquid

0.827 g/mL at 25 °C(lit.)

196 °C(lit.)

−15 °C(lit.)

178 °F

0.14 mm Hg ( 25 °C)

n20/D 1.429(lit.)

2.339

1

1

6

9

43.8

0

O([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H]

KBPLFHHGFOOTCA-UHFFFAOYSA-N

InChI=1S/C8H18O/c1-2-3-4-5-6-7-8-9/h9H,2-8H2,1H3

octan-1-ol

1Octanol; 1 Octanol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~767.87 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (19.20 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (19.20 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (19.20 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)