The brain chemical acetylcholine binds to muscarinic receptors on nerve cells in the brain, causing the brain to send messages to the body that slow the inflammatory response. The receptors can be stimulated though a number of mechanisms, including by use of drugs that mimic the effect of acetylcholine, by blocking an enzyme that naturally destroys acetylcholine, or by provoking the nerve cells to release more acetylcholine. The researchers also tested muscarinic receptors in other parts of the body, but unlike the central receptors in the brain, they do not play an essential role in controlling the inflammatory response.
"Medications in a class of drugs called centrally acting cholinergic agents are already available on the U.S. market, approved by the Food and Drug Administration (FDA) for treating Alzheimer's disease," said Dr. Tracey, who is also Director and Chief Executive Officer of The Feinstein. "Our next step will be to conduct a clinical trial with one of these drugs as an anti-inflammatory agent to evaluate its effect on inflammatory measures in healthy people."
The research team plans to test galantamine, a drug whose active ingredient was first extracted from a plant and is now synthesized in the laboratory, which works primarily by blocking the enzyme that destroys acetylcholine. The drug allows the nerve cells in the brain to communicate their anti-inflammatory signals to the rest of the body. The FDA approved galantamine for mild to moderate Alzheimer's dementia in 2001. Galantamine was approved with the trade name Reminyl and is now known as Razadyne.
"In addition to stopping the natural breakdown of acetylcholine, galantamine stimulates nerve cells in the brain to release more of the chemical messenger," said Dr. Pavlov. "This secondary mechanism of action is unique in this class of drugs."
Before being approved in the United States, galantamine was commercially available in Europe under the trade name Nivalin and used for decades in the fields of anesthesiology, neurology, ophthalmology, gastroenterology, cardiology and others.