Adrenergic agonists and antagonists as antiglaucoma agents: a literature and patent review (2013–2019)

ABSTRACT

Introduction: Glaucoma is a neurodegenerative disease of the eye characterized by selective retinal ganglion cell loss that provokes progressive defects in the visual field. Elevated intraocular pressure (IOP) is an important contributor for the progression of glaucoma. The current therapeutic arsenal for reducing IOP includes prostaglandin analogs, β-blockers, carbonic anhydrase inhibitors, α-adrenergic agonist, miotics, rho-kinase inhibitors and combinations thereof, generally administered as eye drops.

Areas covered: This manuscript reviews the state of art on adrenergic modulators for treating glaucoma. Both monotherapy and fixed-drugs combinations including α₂-adrenergic agonists and β-blockers are discussed as well as drug delivery systems where these classes of drugs are used. The review then covers the patent literature involving adrenoceptors modulators over the period 2013–2019.

Expert opinion: While the scientific community is moving forward novel targets and related modulators for treating glaucoma and ocular hypertension, adrenergic modulators held a prominent position in the therapy of glaucoma and related disorders. Indeed, though not embodying anymore the first-choice monotherapy, they are widely marketed worldwide ordinarily in combination with other drugs, are subjects of many studies for identifying new drug compositions and have been assessed as active ingredients in several innovative ocular drug delivery systems.

KEYWORDS:

• Glaucoma
• ocular hypertension
• α-adrenoceptor
• β-adrenoceptor
• modulator
• combination
• drug delivery system
• multi-target

Article highlights

• Glaucoma is characterized by damage to the optic nerve head and loss of peripheral visual field.

• The pharmacologic treatment of glaucoma includes various classes of drugs generally administered as eye drops.

• Soon after their introduction in the late 1970s, topical β-blockers became the agents of choice for treating glaucoma.

• To date, prostaglandin analogs (PGAs) are the first-line agents for most patients with glaucoma or ocular hypertension.

• Combination therapy is required for adequate IOP control in many patients.

• Adjunctive agents to a PGA typically include β-blockers, α₂-adrenergic agonists and topical carbonic anhydrase inhibitors.

• Many other combinations are used or have been investigated which include β-blockers and α₂-adrenergic agonists.

• Several studies have been carried out on new drug delivery systems including α₂-agonists or β-blockers as active ingredients for lowering IOP.

• Many patents in the period 2013–2019 claim adrenergic modulators for new compositions, combinations, and drug delivery systems for treating glaucoma.

• Multi-target strategies resulted to be effective for lowering IOP but are still in their infancy.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.