Antipsychotic drugs—used to treat the large numbers of individuals in the U.S. with schizophrenia—have a bunch of terrible side effects. Additionally, the drugs do not work well for many people. Better drugs must be developed immediately.
Another finding from Northwestern Medication researchers opens another road to fostering more viable medications to treat the incapacitating side effects of schizophrenia. Generally, specialists have screened antipsychotic drug competitors by assessing their impacts on mouse behavior; however, the methodology utilized by a Northwestern lab beats these customary methodologies as far as foreseeing viability in patients.
The review found that antipsychotic drugs—which restrain the overactive dopamine causing the side effects of schizophrenia—connect with something altogether different than researchers initially accepted.
“This is a significant discovery that fundamentally alters how we perceive the brain underpinnings of psychosis and opens up new avenues for its treatment.”
lead investigator Jones Parker, assistant professor of neuroscience at Northwestern University Feinberg School of Medicine.
“This is a milestone finding that totally updates how we might interpret the brain reason for psychosis and graphs another way for growing new medicines for it,” said lead examiner Jones Parker, collaborator and teacher of neuroscience at Northwestern College Feinberg Institute of Medication. “It opens new choices to foster medications that have fewer unfavorable incidental effects than the ongoing ones.”
The review was recently distributed in Nature Neuroscience.
The striatum, a part of the brain, has higher levels of dopamine in people with schizophrenia. This locale has two essential sorts of particular synapses called neurons: those that have D1 dopamine receptors and those that have D2 dopamine receptors.
Receptors on neurons resemble locks waiting for the key that turns them on. Consider two distinct populations of neurons: D1 receptors, which express locks, and D2 receptors, which do not. Dopamine is a key for the two receptors; however, antipsychotics just block the D2 receptor locks. In this manner, specialists have expected these medications to specifically follow up on neurons that express the D2 receptor. However, in actuality, the other brain cells—those in the striatum that are adjacent and have D1 receptors—were the ones that responded to antipsychotic medications in a way that predicted the clinical effect.
“The authoritative opinion has been that antipsychotic medications specially influence striatal neurons that express D2 dopamine receptors,” Parker said. ” However, when this concept was put to the test by our group, we discovered that the degree to which a drug alters the activity of D2 receptor-expressing striatal neurons has little bearing on whether or not it is an antipsychotic in humans. All things considered, a medication’s impact on the other striatal neuron type, the one that communicates D1 dopamine receptors, is more prescient of whether they really work.”
Schizophrenia is a weakening mind problem that influences roughly 1 out of 100 individuals (more than 2.5 million individuals in the U.S.). While existing antipsychotics are successful for the trademark side effects of schizophrenia, for example, fantasies and fancies, they are insufficient for other side effects of schizophrenia, like deficiencies in mental and social capability.
In addition, current antipsychotics are totally insufficient for over 30% of patients with treatment-safe schizophrenia (in excess of 750,000 individuals in the U.S.). These drugs’ side effects, such as tardive dyskinesia (uncontrollable body movements) and parkinsonism (rigidity, tremors, and slow movement), also limit their use.
The new study found for the first time how antipsychotic drugs affect the brain region thought to be responsible for psychosis in living animals.
“Our review uncovered our lack of understanding of how these medications work and revealed new helpful techniques for growing more powerful antipsychotics,” Parker said.
Other Northwestern creators include first creator Seongsik Yun, Ben Yang, Justin Anair, Madison Martin, Stefan Fleps, Arin Pamukcu, Nai-Hsing Yeh, Anis Project Worker, and Ann Kennedy.
The title of the article is “Antipsychotic drug viability corresponds with the tweak of D1 instead of D2 receptor-communicating striatal projection neurons.”
More information: Seongsik Yun et al, Antipsychotic drug efficacy correlates with the modulation of D1 rather than D2 receptor-expressing striatal projection neurons, Nature Neuroscience (2023). DOI: 10.1038/s41593-023-01390-9
