4-Methoxyphenol

Absorption

The systemic exposure to mequinol was assessed in eight healthy subjects following two weeks of twice-daily topical treatment of a tretinoin and mequinol combination product . About dose of the product corresponding to about 37.3 ug/cm^2 of mequinol was applied to the subjects' backs . The mean Cmax for mequinol was 9.92 ng/mL (range between 4.22 and 23.62 ng/mL) and the Tmax was 2 hours (range between 1 to 2 hours) . The safety of mequinol in this combination formulation is supported by the low systemic exposures of the agent in the subjects .

Toxicity

If a mequinol and tretinoin combination topical product is applied excessively, some potential adverse effects like marked redness, peeling of skin, discomfort, discoloration, or hypopigmentation may occur . Such products are not indicated for oral ingestion .
MSDS data reports that chronic exposure to a dose of 25 UMOL/L in humans can result in mutagenic effects like DNA inhibition in lymphocytes .

The Uses of 4-Methoxyphenol

4-methoxyphenol may be used in the synthesis of butylated hydroxy anisoles via alkylation with methyl tert-butyl ether over a non-zeolitic solid acidic catalyst. This process is eco-friendly when compared to the Friedel-Crafts alkylation reaction. 4-MP may also react with aqueous nitrous acid to form 2-nitro-4-methoxyphenol and benzoquinone in varying ratios depending on the reaction conditions. 4-MP can be used as a building block in designing β-cyclodextrin 4-methoxyphenol conjugates that can be potential ligands for drug complexation.

Background

Mequinol is a phenol used in various applications. It is used as an inhibitor for acrylic monomers and acrylonitirles, as a stabilizer for chlorinated hydrocarbons and ethyl cellulose, as an ultraviolet inhibitor, as a chemical intermediate in the manufacture of antioxidants, pharmaceuticals, plasticizers, and dyestuffs . It is found as an active ingredient in topical drugs used for skin depigmentation indicated for the treatment of solar lentigines.

Indications

Mequinol is currently primarily available only as an active ingredient in combination products combined with tretinoin that are indicated for the treatment of solar lentigines and related hyperpigmented lesions resulting from chronic sun exposure .

Pharmacokinetics

Mequinol is in fact considered a melanocytotoxic chemical which when oxidized in melanocytes results in the formation of toxic entities like quinones . Such cytotoxic compounds subsequently have the potential to damage and destroy pigment cells, therefore causing skin depigmentation . In response, skin cells are naturally capable of protecting themselves against such cytotoxic agents with the help of endogenous intracellular glutathione and the detoxification action of glutathione S-transferase on the cytotoxic compounds . Regardless, it is consequently by way of this seemingly negative and damaging pharmacodynamic profile by which the mechanism of action of mequinol is sometimes described .

Metabolism

Urine samples from melanoma patients treated with mequinol were analyzed and various mequinol metabolites were identified, including 3,4-dihydroxyanisole, the two o-methyl derivatives 3-hydroxy-4-methoxyanisole and 4-hydroxy-3-methoxyanisole, and even hydroquinone which may have originated at least partly from mequinol . All these identified metabolites were excreted predominantly as sulphates and glucuronides - only a small portion of the substances were present in urine in an unconjugated form . Ultimately, the 3,4-dihydroxyanisole is considered the most important metabolite of mequinol .