Sembragiline

Sembragiline

Chemical structure of Sembragiline

Sembragiline (developmental code name RG1577) is a selective, irreversible monoamine oxidase B (MAO-B) inhibitor that was under investigation for the treatment of Alzheimer's disease. It was developed by Roche and reached phase II clinical trials before its development was discontinued.

Pharmacology

Sembragiline is designed to selectively inhibit the enzyme monoamine oxidase B (MAO-B). MAO-B is an enzyme that breaks down monoamines such as dopamine in the brain. By inhibiting MAO-B, sembragiline increases the levels of dopamine and other monoamines, which can help alleviate symptoms associated with neurodegenerative diseases like Alzheimer's disease and Parkinson's disease.

Mechanism of Action

Sembragiline binds irreversibly to the active site of MAO-B, preventing the enzyme from metabolizing its substrates. This leads to increased availability of monoamines, particularly dopamine, in the brain. The selective inhibition of MAO-B over monoamine oxidase A (MAO-A) is crucial, as MAO-A inhibition can lead to undesirable side effects such as hypertensive crisis when certain foods are consumed.

Clinical Development

Sembragiline was evaluated in clinical trials for its potential to treat symptoms of Alzheimer's disease. The trials aimed to assess its efficacy in improving cognitive function and slowing the progression of the disease. However, despite initial promise, the development of sembragiline was halted after phase II trials due to insufficient efficacy in achieving the desired clinical outcomes.

Chemical Properties

Sembragiline is a small molecule with a specific chemical structure that allows it to selectively bind to MAO-B. The chemical structure of sembragiline is depicted in the accompanying image.

Related Pages

• Monoamine oxidase inhibitor
• Alzheimer's disease
• Parkinson's disease
• Dopamine