The study of live mouse brains indicates For nearly 70 years We’ve Been The design of our product targets the wrong neurons Antipsychotic drugs
To unravel the complex web of brain cells to determine how drugs affect them is not an easy task. Researchers led by Northwestern University Neuroscientist Seongsik Yun used fluorescent tags and a mini-microscope to find that the most effective antipsychotics cling more closely to a specific type of cell in the brain than was originally thought.
Like research has suggested You can also check out our other blog posts. There might not be any chemical imbalanceSerotonin levels and our understanding of them schizophreniaIf antipsychotics used widely target different neurons from what is expected, then treatment may need to change.
Yun, Yun’s colleagues and others: “There is urgent need to know the neural circuits which drive psychosis and their effects by antipsychotic drug.” Write on their published paper.
Jones Parker, a senior neuroscientist and author of a study, is an expert in this field. Tell them to get on with it Wired’s Max G. Levy, most antipsychotic medications – including the first one approved in 1954, chlorpromazine – have been discovered serendipitously. “We don’t even know what the drugs do to your brain.”
Scientists noticed that these drugs suppressed Common symptoms of schizophrenia, such as Dopamine, the brain’s main dopamine receptor, was thought to be responsible for mania, delusions and hallucinations.
They learned that these antipsychotics stifled the transmission of dopamine between brain cells. The most potent were compatible with one particular type D2 dopamine receptor.
Spiny projection neurons are brain cells that pack into and extend from the cortex. striatumD1 and D2 receptors are expressed in the brain. D1 receptors stimulate the dopaminergic system in the brain. D2 receptors quieten it.
In schizophrenia, the D2 receptors were linked to antipsychotic drug potency. This led to the belief that the striatum is the culprit. Awash in dopamine, a chemistry imbalance that antipsychotics correct.
There are new drugs designed specifically to target D2 Receptors Did little to relieve psychosis. It was not known whether the antipsychotics used in animal models for psychosis bind more preferentially to D2 receptors.
Yun and Parker’s team used mice to study the effects of four different drugs that treat psychotic illnesses. They observed their behavior and brain cell responses.
Haloperidol (an older, effective antipsychotic) and olanzapine (a newer, less efficacious antipsychotic) had some effect on the D2 spiny neuron, but interactions with these drugs were mainly at D1 cells.
Clozapine was a more powerful antipsychotic drug with fewer adverse effects. Clozapine suppressed the D1 cells and avoided D2 neurones, which “could explain its clinical superiority in particular for schizophrenia resistant to treatment,” researchers said. Say this:.
MP-10, the drug candidate that failed to pass in Clinical trialsThe D2 neurons remained glued for schizophrenia. MP-10 made the abnormal D1 activity even worse.
In other words, a drug’s clinical efficacy was closely related to its interaction with D1 neurons; those which normalized overactive D1 neurons relieved psychosis best – a finding which flips our understanding of these drugs on its head.
Researchers say that “These findings offer a novel explanation of antipsychotic drug effectiveness.” Writer. The researchers suggest D1 spiny neuron cells and not D2-expressing D2 cells “may be the key driver of psychosis”, with normalizing D1 spiny neuron activity being “a key indicator for antipsychotic effectiveness.”
The findings are a blow for decades of research but they help explain why some antipsychotics like Clozapine work and others don’t. But we must also remember dopamine It’s not the only neurotransmitterLink to psychosis
Researchers can use the new findings to improve schizophrenia treatments. The treatments are needed now.
The study has appeared in Nature Neuroscience.
