Absorption, Distribution and Excretion
Local absorption was extremely low under simulated normal clinical use conditions. Dioctanol absorption was extremely low under simulated normal clinical use conditions. Of 209 plasma samples collected 24 hours after a multi-day trial in 10 subjects, only one sample had a dioctanol level above the limit of quantification (19 ng/mL). Long-chain alcohols were detected in the brains of developing rats, reaching their highest levels at 10 days of age (0.0109% of total lipids) and decreasing to 0.0036% at 40 days of age. They were primarily composed of hexadecyl alcohol, octadecyl alcohol, octadecenol, eicosanool, docosanool, and tetracosanool. A mixture of cis-9[1(-14)C]octadecenol and [1(-14)C]docosanool was injected into the brains of 19-day-old rats, and the radioactive material incorporation into brain lipids was measured at 3, 12, and 24 hours. Both alcohols are metabolized in the brain, but at different rates; they are both oxidized to their respective fatty acids, but oleic acid is more readily incorporated into polar lipids. Significant radioactive incorporation occurs in the 18:1 alkyl and 1-alkenyl moieties of ethanolamine phosphate glycerol and the 18:1 alkyl moietylate of choline phosphate glycerol. Even after the 18:1 alcohol disappears from the substrate mixture (12 hours), the 22:0 alcohol is not used to any measurable extent for the formation of alkylglycerols and 1-alkenylglycerols.

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Metabolism/Metabolites
The 22-carbon fatty alcohol docosanool exhibits antiviral activity against a variety of lipid-enveloped viruses (including herpes simplex virus types 1 and 2) in vitro, through a mechanism that interferes with the normal entry of viruses into target cells. We have previously reported that mammalian cells take up significant amounts of radiolabeled docosanool. In this paper, we report that cells extensively metabolize internalized fatty alcohols. This is confirmed by up to 60% incorporation of cell-associated radiolabels into phospholipids co-purified with phosphatidylcholine and phosphatidylethanolamine. Chemical (Vitride) reduction analysis revealed that a significant portion of n-docosanol was oxidized to n-docosanoic acid, which was then incorporated into polar lipids in the form of an acyl group. However, measurable radiolabels showed resistance to Vitride reduction, consistent with the incorporation of n-docosanol into ether lipids. The metabolic conversion rate and extent of n-docosanol varied with cell type and the surfactant used to suspend the compound. Furthermore, the anti-HSV activity of n-docosanol was quantitatively proportional to the observed metabolic amount. These findings suggest that the anti-HSV activity of n-docosanol involves cellular uptake and metabolism of the drug. A mixture of cis-9-[1(-14)C]octadecenol and [1(-14)C]docosanol was injected intracerebrally into the brains of 19-day-old rats. Both alcohols were metabolized in the brain, but at different rates; each compound was oxidized to the corresponding fatty acid. A significant amount of radioactive material was incorporated into the 18:1 alkyl and 1-alkenyl moieties of ethanolamine phosphate and the 18:1 alkyl moieties of choline phosphate.

[1]. Antiviral activity of 1-docosanol, an inhibitor of lipid-enveloped viruses including herpes simplex. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10825-9.

[2]. Clinical efficacy of topical docosanol 10% cream for herpes simplex labialis: A multicenter, randomized, placebo-controlled trial. J Am Acad Dermatol. 2001 Aug;45(2):222-30.

[3]. The toxicity of behenyl alcohol. I. Genotoxicity and subchronic toxicity in rats and dogs. Regul Toxicol Pharmacol. 2002 Aug;36(1):69-79.

Docosanoyl-1-ol is a long-chain primary fatty alcohol, a compound in which a hydroxyl group is substituted at the 1-position of docosanoyl. It is an over-the-counter drug approved by the U.S. Food and Drug Administration (FDA) for shortening the healing time of cold sores. It is both a plant metabolite and an antiviral drug. It is a long-chain primary fatty alcohol belonging to the docosanoyl alcohol class of compounds. Docosanoyl is a drug used for the topical treatment of recurrent herpes simplex virus cold sores (cold sores or pyogenic vesicles). Docosanoyl is a saturated 22-carbon fatty alcohol with antiviral activity against various lipid-enveloped viruses, including herpes simplex virus (HSV). Docosanoyl inhibits the fusion of the cell membrane with the HSV envelope, thereby preventing viral entry into cells and inhibiting its replication. Docosanoyl has been reported to be found in datura, hibiscus, and other organisms with relevant data. Docosanoyl is a saturated 22-carbon fatty alcohol with antiviral activity. Docosanool possesses a unique antiviral mechanism, inhibiting the fusion of the cell membrane with the herpes simplex virus envelope, thereby preventing viral entry into cells and inhibiting its activity and replication. Docosanool is used topically for the treatment of recurrent herpes simplex virus cold sores, relieving associated pain and potentially aiding in wound healing.

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Drug Indications
For the topical treatment of recurrent oral-facial herpes simplex virus cold sores (cold sores or pyogenic vesicles).
FDA LabelMechanism of Action
Docosanool works by inhibiting the fusion of the human cell membrane with the herpes simplex virus (HSV) envelope, thereby preventing viral entry into cells and subsequent viral replication. Unlike other antiviral drugs for cold sores, docosanool does not act directly on the virus, thus reducing the likelihood of developing resistant HSV mutants.
Cells treated with n-docosanool are resistant to infection by a variety of lipid-enveloped viruses, including herpesviruses. Previous studies on the mechanism of action have shown that n-docosanool inhibits events that occur before the expression of early intermediate gene products and after HSV attachment. This study reports that docosanool inhibits the fusion of the HSV envelope with the cell membrane. Evidence suggests that the antiviral activity requires time-dependent metabolic transformation of this compound. Cellular resistance to infection decreased after drug removal, with a half-life of approximately 3 hours. A 70% reduction in the expression of a constitutively promoter-regulated reporter gene inserted into the viral genome confirmed the decrease in viral gene expression in docosanool-treated cells. A 75% reduction in β-galactosidase expression in target cells carrying the stably transfected lacZ gene (controlled by the HSV early promoter) indicated that the release of virus particle-associated regulatory proteins (an event occurring immediately after viral entry into the cell) was inhibited in treated cells. Finally, the fusion-dependent dequenching of the lipophilic fluorescent probe inserted into the HSV envelope—octadecylrhodamine B chloride—was significantly inhibited in treated cells. Inhibition of the fusion between the cell membrane and the HSV envelope, and the subsequent absence of replication events, are likely the main mechanisms underlying the anti-HSV activity of docosanool.
Dosicosanol reduces viral replication and activity by effectively inhibiting the fusion between the plasma membrane and the herpes simplex virus envelope.

C22H46O

326.609

326.354

661-19-8

1-Docosanol-d45

12620

White to off-white solid powder

0.8±0.1 g/cm3

375.9±5.0 °C at 760 mmHg

65-72 °C(lit.)

142.5±5.2 °C

0.0±1.9 mmHg at 25°C

1.455

10.44

1

1

20

23

190

0

NOPFSRXAKWQILS-UHFFFAOYSA-N

InChI=1S/C22H46O/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20-21-22-23/h23H,2-22H2,1H3

docosan-1-ol

NAA 422 Abreva Nacol-22-97 Nacol 22 97NAA-422 DocosanolNacol2297

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)

Ethanol : ~50 mg/mL (~153.09 mM)
DMSO :< 1 mg/mL H2O : < 0.1 mg/mL

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.65 mM) (saturation unknown) in 10% EtOH + 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 EtOH + 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.)