Molecules blocking a receptor found in the brain called 5-HT6R could potentially be used to treat Alzheimer’s disease, according to two studies led by researchers at Moscow Institute of Physics and Technology (MIPT), according to a news release.
The first study “AVN-211, Novel and Highly Selective 5-HT6 Receptor Small Molecule Antagonist, for the Treatment of Alzheimer’s Disease,” published in the scientific journal Molecular Pharmaceutics, describes the effects of a molecule called AVN-211 in cells grown in the laboratory as well as in animal models of the disease.
The researchers first demonstrated that AVN-211 is indeed capable of blocking the 5-HT6R receptor in cells. They found that the compound was able to block the receptor more selectively and effectively than other compounds, even those that are currently in clinical trials. They then analyzed how the compound is metabolized and with which other molecules it interacts.
The researchers then moved onto animal experiments where they observed the pharmacokinetics, or concentration changes of the compound in the blood of the animals. They also tested the toxicity of the compound and found that it was low.
Finally, they conducted memory disorder stress tests and showed that AVN-211 may be able to improve memory function in mice and rats. First, they trained the animals to find an exit from a maze while they were under the influence of drugs causing memory loss. When they gave these animals AVN-211, the researchers saw that they were able to find the exit to the maze faster. Similarly, animals that were not given a memory loss drug also did better in learning and memory tests when given AVN-211.
The authors concluded that AVN-211 could also combat memory loss in people with Alzheimer’s disease.
The second study tested another compound, which also blocks the 5-HT6R receptor called AVN-322. Published in the scientific journal Current Alzheimer Research, the study, “Preclinical evaluation of AVN-322, novel and highly selective 5-HT6 receptor antagonist, for the treatment of Alzheimer’s disease” showed that AVN-322 was a highly effective molecule blocking the activity of 5-HT6R.
The team conducted experiments similar to AVN-211 on learning and memory in mice and found that AVN-322 also improved the performance of the animals.
The researchers analyzed the pharmacokinetics of AVN-322 in mice, rats, dogs, and monkeys and found that the compound had generally low toxicity. Adverse side effects included a slowing of the heart rate and low blood pressure in rats after three months, but this was less serious than with other existing drugs.
The researchers concluded that AVN-322 has a good pharmacokinetic profile, that it is very digestible and that it passes well through the blood-brain barrier.
As a next step, the researchers are hoping to test the safety and effectiveness of the two compounds in human clinical trials.
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