Ethosuximide and Phenobarbital Promote Wound Healing via Enhancing Collagenization

The fact that ethosuximide (ETO), phenobarbital (PHO), and barbituric acid (BARB) share structural and pharmacophoric homologies with phenytoin and allantoin, both known to have significant wound-healing properties, prompted us to evaluate them as wound-healing agents. Accordingly, ETO-, PHO-, and BARB-containing ointments were applied onto full-thickness excision and incision wounds created on the dorso-lumbar region of experimental rats. ETO-and PHO-treated incision wounds illustrated significant enhancement in breaking strengths (1380 +/- 61 and 1240 +/- 42 g, respectively) compared to vehicle controls (1070 +/- 18 g) and BARB (1080 +/- 45 g). Moreover, biochemical analyses revealed significant increase in hydroxyproline contents in ETO- and PHO-treated wounds compared to vehicle controls. Histological evaluation revealed that both ETO and PHO promoted collagen synthesis and deposition. This is the first time to describe the significant wound-healing merits of ETO and PHO as potential clinical agents for treatment of chronic wounds.