KarXTa drug recently approved to treat schizophrenia, is generating high expectations about its potential to also treat Alzheimer’s disease. This drug represents a significant advance in psychiatry, as it targets muscarinic receptors in the brain, allowing it to have both antipsychotic and cognitive effects.
This innovation has revived research in muscarinic drugsa class of medications that had taken a back seat in the treatment of brain disorders.
The development of KarXT began with research into xanomeline, a compound that, in the 1990s, was shown to reduce psychotic symptoms in people with Alzheimer’s. However, xanomeline caused side effects such as nausea and vomiting due to its action on muscarinic receptors throughout the body. To avoid these effects, the company Karuna Therapeutics combined xanomeline with trospium, a compound that blocks these receptors outside the brain, minimizing side effects in the body.
This approach, known as KarXT, has been shown to offer antipsychotic and cognitive benefits in patients with schizophrenia, with fewer adverse effects than the original treatment, report an article in ‘Nature‘.
The approval of this drug in the USA meant, for Eduard Vieta, Researcher at the Biomedical Research Center in Mental Health Network (CIBERSAM). Head of Psychiatry and Psychology Service of the Hospital Clínic of Barcelona and professor at the University of Barcelona«an important advance in the treatment of schizophrenia, since it is the first medication that does not act directly on dopaminergic receptors, but on muscarinic ones. In statements to Science Media CenterVieta said that this sense, although acetylcholine and dopamine are interconnected, involves a very relevant innovation since it represents a mechanism of action from the current drugs and a profile of adverse effects that is also different, which may constitute a good alternative for patients who do not tolerate the drugs currently used.
Furthermore, the effect size in the acute phase and the results of the extension study regarding long-term safety and effectiveness are also positive. After its approval, clinical experience will show to what extent it has represented a true advance for clinical practice in this disease so in need of new approaches.
The success of KarXT has renewed interest in muscarinic drugswhich are known to influence cognition and reward circuits in the brain. Researchers have noted that the drug could have applications beyond schizophrenia, especially in treating psychosis associated with Alzheimer’s disease and disorders such as bipolar.
In addition, M1 muscarinic receptors, related to cognition, are being investigated to treat cognitive impairment in patients with Alzheimer’s. It is hoped that drugs that target these receptors can slow the progression of the neurodegenerative disease.
Despite the enthusiasm that KarXT has generated, researchers warn that developing new drugs is a long and challenging process.
Thus, for José García-Valdecasas, deputy secretary of the Board of the Spanish Association of Neuropsychiatry“a new drug comes out with a novel mechanism of action, which in principle is fine, but in these cases we must avoid conveying an image of excessive effectiveness or excessive hope in the face of the novelty. Just because something is new doesn’t necessarily mean it’s better.. “You have to focus on the studies and the available data.”
Same as placebo
For example, a recent clinical trial of the drug emraclidineanother muscarinic drug for schizophrenia, failed to outperform placebo, raising questions about the effectiveness of other similar drugs. Scientists are investigating allosteric modulators, which affect muscarinic receptors more specifically, with the goal of reducing side effects and improving efficacy.
The future of KarXT and other muscarinic drugs remains uncertain. While clinical trials have shown promising results, the true test of these drugs will be their performance in the real worldwhere patients are not isolated in controlled environments. Researchers continue to observe the effects of KarXT in outpatients with schizophrenia and are also studying its impact on Alzheimer’s disease.
Although the development of these treatments is still in its early stages, progress in the use of muscarinic drugs to treat brain disorders offers new hope in the treatment of complex diseases such as schizophrenia and Alzheimer’s.
However, the Scientists stress the need for more research to understand how these drugs affect patients in the long term and whether they can actually slow or stop the progression of diseases such as Alzheimer’s.
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