Introduction: Glaucoma is one of the main leading causes of irreversible blindness in the world. The treatment of this disease relies on the use of drugs able to reduce/control the intraocular pressure (IOP), one of the main risk factors for glaucoma. Current therapies are based on the use of compounds belonging to well-established categories (prostaglandin analogs, β-adrenergic blockers, α-adrenergic agonists, carbonic anhydrase inhibitors, Rho kinase inhibitors, and cholinergic agonists). However, even if they are effective in reducing IOP, important side effects impair patient compliance, accounting for the necessity of novel therapy approaches. Therefore, new targets are emerging as alternative and more complete routes to fight glaucoma disease. Areas covered: This review provides a comprehensive update on the development state of innovative strategies against glaucoma describing results, administration routes, pharmaceutical compositions, structures, and SARs as well as the related shortcomings within the 2013-2019 range. Expert opinion: New innovative pharmacological targets have been explored in the last six years, allowing a broader therapeutic arsenal against glaucoma and IOP-related pathologies. The endocannabinoid system and FAAH inhibitors were the most investigated from a medicinal chemistry point of view.
Keywords: FAAH inhibitors; Glaucoma; RNA interference; adenosine receptor; endocannabinoids; melatonin receptor agonists.