Tolnaftate was first synthesized by Japan Soda and first described as a topical antimycotic in 1962. Tolnaftate is stable under normal storage conditions, but schould be protected from light. 

Synthesis

Tolnaftate is synthesized from β-naphthol, thiophosgene, and N-methl-mtolulidine by the following pathway. Another route, which does not use thiophosgene, has been described.

Antimycotic Properties

In vitro, tolnaftate has a narrow activity spectrum with fungistatic effect on towards dermatophytes and a few moulds such as some isolates of selected Aspergillus species. The MIC values range between 0.1 and 3 μg/mL for susceptible fungi. Isolates of susceptible species showing primary resistance or developing secondary resistance are rarely observed. Tolnaftate is almost ineffective against yeasts and moulds.

Indications

The indications for tolnaftate are defined by its narrow spectrum and limited to the treatment of dermatophytoses. Tolnaftate is effective when topically administered several times daily over a period of several weeks. Because of its inadequate penetration into nail keratin, tolnaftate is unlikely to be effective for the treatment of onychomycoses. On the average, the efficacy of tolnaftate in topical therapy of dermatomycoses is lower than that of most other antimycotics for topical treatment.