Absorption, Distribution and Excretion
Topical absorption has been shown to be minimal under conditions reflecting normal clinical use.
Absorption of docosanol has been shown to be minimal under conditions reflecting normal clinical use. Of 209 plasma samples taken from ten subjects 24 hours after a multi-day test, only one had a docosanol level above the quantitation limits (19 nanograms/mL).
Long chain alcohols were detected in developing rat brain at their highest level of 0.0109% of the total lipids at the age of 10 days and decreased to 0.0036% at the age of 40 days. They consited mainly of hexadecanol, octadecanol, octadecenol, eicosanol, docosanol, and tetracosanol.
A mixture of cis-9[1(-14)C] octadecenol and [1(-14)C] docosanol was injected into the brains of 19-day-old rats, and incorporation of radioactivity into brain lipids was determined after 3, 12, and 24 hr. Both alcohols were metabolized by the brain but at different rates; each was oxidized to the corresponding fatty acid, but oleic acid was more readily incorporated into polar lipids. Substantial amounts of radioactivity were incorporated into 18:1 alkyl and alk-1-enyl moieties of the ethanolamine phosphoglycerides and into 18:1 alkyl moieties of the choline phosphoglycerides. Even after the disappearance of the 18:1 alcohol from the substrate mixture (12 hr), the 22:0 alcohol was not used to any measurable extent for alkyl and alk-1-enylglycerol formation.

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Metabolism / Metabolites
The 22-carbon fatty alcohol, n-docosanol, exhibits in vitro antiviral activity against several lipid-enveloped viruses including herpes simplex viruses 1 and 2 by a mechanism that interferes with normal viral entry into target cells. We previously reported that mammalian cells incorporate significant quantities of radiolabeled n-docosanol. Herein, we report that cells extensively metabolize the internalized fatty alcohol. This is evidenced by incorporation of up to 60% of cell-associated radiolabel into phospholipids that copurify with phosphatidylcholine and phosphatidylethanolamine. Analysis by chemical (Vitride) reduction suggests that a significant portion of n-docosanol is oxidized to n-docosanoic acid and then incorporated as an acyl group on polar lipids. A measurable amount of radiolabel, however, is resistant to Vitride reduction, consistent with incorporation of n-docosanol into ether lipids. The rate and extent of metabolic conversion of n-docosanol vary with the cell type and surfactant used to suspend the compound. Furthermore, the anti-HSV activity of n-docosanol is quantitatively proportional to the amount of metabolism observed. 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 into the brains of 19-day-old rats. Both alcohols were metabolized by the brain but at different rates; each was oxidized to the corresponding fatty acid. Substantial amounts of radioactivity were incorporated into 18:1 alkyl and alk-1-enyl moieties of the ethanolamine phosphoglycerides and into 18:1 alkyl moieties of the choline phosphoglycerides.

[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.

Docosan-1-ol is a long-chain primary fatty alcohol that is docosane substituted by a hydroxy group at position 1. It is a non-prescription medicine approved by the FDA to shorten healing time of cold sores. It has a role as a plant metabolite and an antiviral drug. It is a long-chain primary fatty alcohol and a docosanol.
Docosanol is a drug used for topical treatment for recurrent herpes simplex labialis episodes (episodes of cold sores or fever blisters). A saturated 22-carbon aliphatic alcohol, docosanol exhibits antiviral activity against many lipid enveloped viruses including herpes simplex virus (HSV). Docosanol inhibits fusion between the plasma membrane and the herpes simplex virus (HSV) envelope, thereby preventing viral entry into cells and subsequent viral replication.
Docosanol has been reported in Mandragora autumnalis, Hibiscus cannabinus, and other organisms with data available.
Docosanol is a saturated 22-carbon aliphatic alcohol with antiviral activity. Docosanol has a distinct mechanism of action and inhibits fusion between the plasma membrane and the herpes simplex virus envelope, thereby preventing viral entry into cells and subsequent viral activity and replication. Docosanol is used topically in the treatment of recurrent herpes simplex labialis episodes and relieves associated pain and may help heal sores faster.

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Drug Indication
For the topical treatment of recurrent oral-facial herpes simplex episodes (cold sores or fever blisters).
FDA Label

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Mechanism of Action
Docosanol works by inhibiting fusion between the human cell plasma membrane and the herpes simplex virus (HSV) envelope, thereby preventing viral entry into cells and subsequent viral replication. Unlike other cold-sore antivirals, docosanol does not act directly on the virus, and as such it is unlikely it will produce drug resistant mutants of HSV.
n-Docosanol-treated cells resist infection by a variety of lipid-enveloped viruses including the herpesviruses. Previous studies of the mechanism of action demonstrated that n-docosanol inhibits an event prior to the expression of intermediate early gene products but subsequent to HSV attachment. The studies reported here indicate that n-docosanol inhibits fusion of the HSV envelope with the plasma membrane. Evidence suggests that antiviral activity requires a time-dependent metabolic conversion of the compound. Cellular resistance to infection declines after removal of the drug with a t1/2 of approximately 3 h. Reduced expression of viral genes in n-docosanol-treated cells was confirmed by a 70% reduction in expression of a reporter gene regulated by a constitutive promoter inserted into the viral genome. Inhibited release in treated cells of virion-associated regulatory proteins--an immediate post entry event--was indicated by a 75% reduction in the expression of beta-galactosidase in target cells carrying a stably transfected lacZ gene under control of an HSV immediate--early promoter. Finally, the fusion-dependent dequenching of a lipophilic fluorescent probe, octadecyl rhodamine B chloride, inserted into the HSV envelope was significantly inhibited in treated cells. Inhibition of fusion between the plasma membrane and the HSV envelope, and the subsequent lack of replicative events, may be the predominant mechanism for the anti-HSV activity of n-docosanol.
Docosanol 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.)