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
In vitro dermal flux in human skin (epidermis) was reported as 0.008 mg/sq cm/hr, suggesting a low rate of penetration.

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Metabolism / Metabolites
The primary aliphatic alcohols undergo two general reactions in vivo, namely oxidation to carboxylic acids and direct conjugation with glucuronic acid. The first reaction proceeds with the intermediate formation of an aldehyde, and the carboxylic acid from the aldehyde may be either oxidized completely to carbon dioxide or excreted as such or combined with glucuronic acid as an ester glucuronide. The extent to which an alcohol undergoes the second reaction, i.e. direct conjugation to an ether glucuronide, appears to depend upon the speed of the first reaction. Alcohols which are rapidly oxidized form very little ether glucuronide unless given in high doses.
The urinary metabolites of n-octane in Fischer 344 rats given the hydrocarbon by gavage included 2-octanol, 3-octanol, 5-oxohexanoic acid, and 6-oxoheptanoic acid. The sex of the animals influenced the relative amounts of metabolites formed. Analyses were performed by gas-liquid chromatography (GC) and gas-liquid chromatography/mass spectrometry (GC/MS). This is the first reported finding of keto acids in hydrocarbon oxidative metabolism. No kidney damage was found as a result of n-octane dosing although the 2,2,4-trimethylpentane (iso-octane) isomer does cause kidney lesions in male rats. /n-Octane/

Toxicity Summary
IDENTIFICATION AND USE: 1-Octanol is a colorless liquid used in the determination of partition coefficients, perfumery, cosmetics, organic synthesis, solvent manufacture of high-boiling esters, antifoaming agent, and as a flavoring agent. 1-octanol is registered for pesticide use in the USA but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses. It has been used as experimental medication to treat tremor in patients. HUMAN EXPOSURE AND TOXICITY: In a human patch test, 1-octanol in 2% petrolatum was neither a skin irritant nor a skin sensitizer. Octanol has caused transient injury of corneal epithelium, with recovery in 48 hr. Common signs of exposure to 1-octanol are CNS: headache, muscle weakness, giddiness, ataxia, confusion, delirium, coma. Gastrointestinal: nausea, vomiting, diarrhea (odor of the alcohol in excreta). Irritation of skin, eyes, throat from vapor or liquid with cough and dyspnea. The annoying odor of 1-octanol may mask sensory irritation and prevent subjects with enhanced chemical sensitivity from concentrating on performance in a demanding task. ANIMAL STUDIES: 1-Octanol was slightly irritating to the skin of rabbits and is considered an eye irritant using the EU criteria. n-Octanol (0.55 g/kg) produced the largest decrease in body temperature. No evidence of tumors in the lung adenoma study in which mice were injected intraperitoneally with 100 and 500 mg/kg 1-octanol three times a week for 8 weeks. Studies indicate that T-type calcium channels (T-channels) in the thalamus are cellular targets for general anesthetics. The study recorded T-currents and underlying low-threshold calcium spikes from neurons of nucleus reticularis thalami (nRT) in brain slices from young rats and investigated the mechanisms of their modulation by an anesthetic alcohol, 1-octanol. 1-Octanol inhibited native T-currents at subanesthetic concentrations with an IC(50) of approximately 4 uM. Inhibition of both native and recombinant T-currents was accompanied by a hyperpolarizing shift in steady-state inactivation, indicating that 1-octanol stabilized inactive states of the channel. In developmental studies in rats no treatment-related effects were observed in pregnant females, including frequency of resorptions, fetal weights, or skeletal/visceral malformations. 1-Octanol was negative in an Ames Salmonella assay with strains Ta 98, TA 100, TA 1535, TA 1537, and TA 1538 at concentrations ranging from 4 to 2500 ug/plate with and without metabolic activation.

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

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Interactions
... Whether 1-octanol (OCT) could inhibit Ethanol (ETOH) toxicity in cultured whole mouse embryos /was studied/. Embryos (3 to 5 somites) were cultured for 6 hours in the absence and presence of alcohols and transferred to control medium for an additional 20 hours. Somite pairs were counted after a total of 26 hours in culture ... Treatment with 3 uM OCT did not produce a delay in embryonic development, whereas 10 uM and 50 uM OCT caused increasing toxicity. Embryos cultured for 6 hours with 100 mM ETOH showed markedly delayed in vitro development (13.8 + or - 0.7 somite pairs after 26 hours, n = 15) as compared with control embryos (19.6 + or - 0.6 somite pairs, n = 5). The toxicity of 100 mM ETOH was significantly reduced by co-incubation with 3 uM OCT (16.9 + or - 0.6 somite pairs; n = 23, p less than 0.002). All of the control embryos and 60.9% of the ethanol/octanol-treated embryos had greater than or equal to 17 somite pairs; in contrast, only 13.4% of the embryos treated with ethanol alone had greater than or equal to 17 somite pairs. Conversely, while 33.3% of the embryos treated with ethanol alone had less than or equal to 12 somite pairs, none of the control embryos and only 4.3% of the embryos treated with ethanol plus octanol were this small.

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Non-Human Toxicity Values
LD50 Rat oral >5 g/kg
LD50 Mouse oral 1,800 mg/kg
LD50 Rabbit dermal >5 g/kg
LD50 Mouse iv 69 mg/kg
LD50 Guinea pig dermal >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.

Octanol appears as a clear colorless liquid with a penetrating aromatic odor. Insoluble in water and floats on water. Vapors heavier than air. Vapors may irritate the eyes, nose, and respiratory system.
Octan-1-ol is an octanol carrying the hydroxy group at position 1. It has a role as a plant metabolite, an antifungal agent, a kairomone, a fuel additive and a bacterial metabolite. It is an octanol and a primary alcohol.
Caprylic alcohol has been used in trials studying the treatment of Essential Tremor.
1-Octanol has been reported in Senegalia berlandieri, Alpinia latilabris, and other organisms with data available.
octan-1-ol is a metabolite found in or produced by Saccharomyces cerevisiae.
A colorless, slightly viscous liquid used as a defoaming or wetting agent. It is also used as a solvent for protective coatings, waxes, and oils, and as a raw material for plasticizers. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)
See also: Alcohols, C6-12 (annotation moved to); Alcohols, C8-18 and C18-unsatd. (annotation moved to).

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Mechanism of Action
The effect of various alkanols on the central nervous system was studied by using rat brain synaptosomal membranes as an in vitro model. The activity of (Ca2+/Mg2+)ATPase and the membrane fluidity were determined. The n-alkanols exhibited an increased molar inhibition of the ATPase activity with an increase in the carbon chain length up to 1-octanol. 1-octanol and 1-decanol caused a biphasic effect on the ATPase activity depending on the alkanol concentration, whereas 1-dodecanol caused a stimulation of the ATPase activity. All alkanols studied caused an increased fluidity of the membrane ... /These/ results indicate that the effect of alkanols on the ATPase activity depends on changes in the border layer between the membrane and the surrounding medium and on a binding of the alkanols to the enzyme molecule ... The two-way effect of 1-octanol and 1-decanol and the stimulatory effect of 1-dodecanol indicate that more mechanisms are involved ... Changes in the membrane fluidity do not seem to be a prerequisite of the ATPase inhibition.
... Studies indicate that T-type calcium channels (T-channels) in the thalamus are cellular targets for general anesthetics. Here, we recorded T-currents and underlying low-threshold calcium spikes from neurons of nucleus reticularis thalami (nRT) in brain slices from young rats and investigated the mechanisms of their modulation by an anesthetic alcohol, 1-octanol. We found that 1-octanol inhibited native T-currents at subanesthetic concentrations with an IC(50) of approximately 4 muM. In contrast, 1-octanol was up to 30-fold less potent in inhibiting recombinant Ca(V)3.3 T-channels heterologously expressed in human embryonic kidney cells. Inhibition of both native and recombinant T-currents was accompanied by a hyperpolarizing shift in steady-state inactivation, indicating that 1-octanol stabilized inactive states of the channel. To explore the mechanisms underlying higher 1-octanol potency in inhibiting native nRT T-currents, we tested the effect of the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) and PKC inhibitors. We found that PMA caused a modest increase of T-current, whereas the inactive PMA analog 4alpha-PMA failed to affect T-current in nRT neurons. In contrast, 12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo(2,3-a)pyrrolo(3,4-c)-carbazole (Go 6976), an inhibitor of calcium-dependent PKC, decreased baseline T-current amplitude in nRT cells and abolished the effects of subsequently applied 1-octanol. The effects of 1-octanol were also abolished by chelation of intracellular calcium ions with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid. Taken together, these results suggest that inhibition of calcium-dependent PKC signaling is a possible molecular substrate for modulation of T-channels in nRT neurons by 1-octanol.

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Therapeutic Uses
Mesh Heading: Pharm. Action: Solvents
EXPL THER 1-Octanol (an 8-C alcohol currently used as a food-flavoring agent) is known to inhibit tremor in essential tremor (ET) animal models at a much lower dose than ethyl alcohol. The /study/ conducted a randomized, placebo-controlled pilot trial of a single oral dose of 1 mg/kg of 1-octanol in 12 patients with ET. No significant side effects or signs of intoxication were observed. 1-Octanol significantly decreased tremor amplitude for up to 90 minutes. The results suggest 1-octanol as 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.)