Nitroxide Pharmaceutical Development for Age-Related Degeneration and Disease

Nitroxide small molecule agents, such as Tempol (TP), Tempol Hydroxylamine (TP-H), and TP-H prodrug (OT-551), were developed to prevent or treat age-related macular degeneration (AMD) and cardiovascular disease. These drugs addressed conditions induced by aging, smoking, diet, oxidative stress, and chronic inflammation. Studies showed that TP could reverse cutaneous microvascular dysfunction in smokers, prevent radiation-induced skin burns and hair loss in elderly cancer patients, and that OT-551 eye drops could prevent vision loss in AMD patients. The human data indicated that these nitroxide drugs were safe and effective, with TP and TP-H effectively penetrating skin and mucosa but not the cornea, while OT-551 penetrated the eye, preserving visual acuity in AMD patients. Various drug formulations, including topical, oral, and injectable, were discussed.