Retinal degenerations and light-induced damages of the retina include diseases such as photoretinitis, retinitis pigmentosa, age-related maculopathy (ARM) and age-related macular degeneration (AMD).
Among these diseases, AMD is particularly important since it represents the leading cause of vision loss after 55 years of age in industrialized countries. The global prevalence of the disease is 8% after 50 and increases with age, from about 1 to 2% between 50 and 65, to 10% between 65 and 75, then to 25% between 75 and 85.
The etiology of AMD is unknown but several risk factors have been identified or are suspected, including age, smoking habits, arterial hypertension, the light color of the iris, antecedents of coronary events, and significant exposure to light. In addition, genetic factors also play a role in the onset of the disease.
There are several stages in AMD: early stages, which correspond to age-related maculopathy (ARM), as well as later stages, corresponding to AMD in the strict sense, which include non-exudative forms, also called dry forms, or atrophic forms in their advanced stage, and exudative forms, also called wet or neovascular forms.
In France, there is, at present, no drug treatment approved for the treatment of atrophic AMD. As for the exudative form of AMD, anti-VEGFs (Vascular Endothelial Growth Factor) administered by the intravitreal route are the only first-line treatment recommended by the High Authority of Health (HAS). It has thus been shown that ranibizumab, a Fab fragment of an anti-VEGF-A monoclonal antibody, monthly administered by intravitreal injections of 0.3 mg and 0.5 mg allows a visual acuity improvement of +8.1 and +10.7 letters respectively in patients suffering from neovascular (exudative) AMD, while a loss of visual acuity of 9.8 letters was observed in control patients treated with dynamic phototherapy (for review see Fong & Lai (2013) Clinical Interventions in Aging 8:467-483).
Accordingly, there is an unmet need in regard of the pharmacological management of the non-exudative form, in particular the atrophic form, of AMD. Furthermore, as for the exudative form, it would be useful to have a treatment for limiting, or even stopping, the use of intravitreal injections that are particularly uncomfortable for the patient.
In this context, given the protective action of phenyl-N-tert-butyl-nitrone in light-induced degeneration of the retina in rats after intraperitoneal injection (Ranchon et al. (2001) Investigative Ophthalmology & Visual Science 42:1375-1379), it has been proposed to use it in AMD treatment, in particular for its dry form. However, no clinical trials have been performed for this compound that could lead to its use in humans.
Etifoxine or 6-chloro-2-ethylamino-4-methyl-4-phenyl-4H-[3,1]benzoxazine hydrochloride belongs to the family of aminobenzoxazines. It promotes GABA transmission by binding to a site near the chloride channel coupled to GABAA receptor and is currently used as an anxiolytic. Few adverse events following its use are listed.

The synthesis of this compound is described in French patent n°1 571 287. Moreover, several active metabolites of etifoxine have been described, such as desethyl-etifoxine or 2-amino-6-chloro-4-methyl-4-phenyl-4H-[3,1]benzoxazine, 6-chloro-4-(4-hydroxyphenyl)-4-methyl-3,4-dihydro-1H-quinazolin-2-one or 6-chloro-3-ethyl-7-hydroxy-4-methyl-4-phenyl-3,4-dihydro-1H-quinazolin-2-one.