From the early to the early 1960s, scopolamine was used as an analgesic for maternal delivery. Scopolamine traps people in a semi-anesthetic state, leaving the patient awake while losing the ability to sense pain.
However, during the course of medication, doctors found an interesting phenomenon: After giving medication, the mothers will completely forget their own delivery process. No one knows the cause of this phenomenon, but scientists are well aware that scopolamine interferes with the acetylcholine signaling pathway in the nervous system.
In the 1970s, Per Anderson and Terje Lomo proposed the Long term potentiation theory of memory formation. Combining the role of acetylcholine in nerve signal transduction, scientists began to wonder whether the loss of acetylcholine was the key to memory loss in Alzheimer's patients.
However, to verify this issue, there are a series of other issues that have yet to be resolved. First, the presence of acetylcholine deficiency in the patient's brain. After a series of studies in the brain after the death of the patient, the answer is undoubtedly determined.
Another question is whether acetylcholine signaling pathways that impede healthy human brains actually affect memory? To answer this question, researchers at Southwestern University in the United States recruited a group of healthy volunteers in 1974 to take scopolamine. The results showed that compared with placebo group, the short-term memory of volunteers in the medication group did significantly decline. Once again, the answer is unquestionable.
The next most important question is whether improving the level of acetylcholine in the patient's brain will improve their memory. The simplest way is to verify it through diet. Neurons need choline for the synthesis of acetylcholine, and choline has a very rich food source, including eggs, beef, fish, and more.
From 1978 to 1982, Europe and the United States conducted a series of clinical studies to verify the therapeutic effects of dietary choline on Alzheimer's disease. However, none of these tests failed. Therefore, scientists speculate that a more reasonable explanation is that neurons may have stopped synthesizing acetylcholine during the onset of Alzheimer's disease. Choline supplementation does not increase acetylcholine levels in the brain. So is it feasible to maintain the level of acetylcholine present in the brain?
William Summers, a neuroscientist in the United States, proposed a strategy in 1981 that uses drugs to inhibit the activity of acetylcholinesterase, thereby maintaining acetylcholine levels. And Summers has a special liking for tacrine.
Tacrine was synthesized in the course of the development of anti-infective drugs before World War II and was put on hold after the discovery of penicillin. But in animal experiments, scientists discovered that tacrine can relieve anesthesia in experimental animals.
Later, an Australian psychiatrist Sam Gershon discovered that the effect was due to its pharmacological inhibition of acetylcholinesterase. In fact, Tarcine's mechanism of action is similar to that of the nerve gas Sarin, but its risk is lower.
So Summers started clinical research and published preliminary clinical trial data in the New England Journal of Medicine in 1986. The article immediately caused a huge sensation, the results show that tacrine can indeed improve the patient's memory and cognitive function.
Although it cannot be cured, it is undoubtedly the dawn of victory for millions of patients and desperate families. FDA approved tacrine on September 10, 1993, making it the first drug to treat Alzheimer's disease. However, due to the side effects of the drug, it was withdrawn from the US market in May 2012.
Up to now, there are five drugs approved by the FDA for the treatment of Alzheimer's disease. Memantine, as an NMDA receptor inhibitor, is similar to the mechanism of cholinesterase inhibitors. The efficacy of these drugs is actually not very good, although it can improve patients' memory and cognitive function to some extent, but it can not delay the progression of the disease.
So how can we actually slow the development of the disease and even cure Alzheimer's disease? In order to solve this problem, we have to return to basic research on the disease itself.