Rationale for the use of Memantine in the Treatment of Chronic Glaucoma

William A. Hare OD, PhD

I. Glutamatergic Excitotoxicity and Neuronal Injury

- Types of glutamate receptors on Neurons (RGCs).

- Excessive activation of glutamate receptors results in irreversible neuronal injury.

- Evidence to support glutamatergic excitotoxic contribution to neuronal injury in models of CNS injury/disease.

II. Physiology of NMDA-gated glutamatergic receptors/channels.

- Ionic conductance.

- Voltage-dependent block by magnesium ions.

- Significance for synaptic signaling.

- Mechanism for excitotoxic neuronal injury.

III. Pharmacology of memantine

- "Open-channel" blocker.

- "Use dependence".

- Voltage-dependence of channel blockade.

- Binding and unbinding kinetics.

- Safety profile.

IV. Results from studies in animal models of injury to the retina and optic nerve.

- Acute retinal ischemia.

- Experimental glaucoma (rat)

- Experimental glaucoma (monkey)

V. Clinical trials using memantine

- Parkinson’s Disease

- Alzheimer’s Disease

- Chronic Glaucoma