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Neurotoxicity of antipsychotics

M

Memantine

Bluelighter
Joined
May 16, 2015
Messages
304
Hi,

I want to know why some neuroleptic drugs are concidered neurotoxic and others neuroprotective(for example haloperidol vs risperidone).

Does anyone know a list of neurotoxic antipsychotics? Can you tell by the drugs pharmacology/binding profile whether it is neurotoxic or not?
 
I believe that most of the theorie of neurotoxic damage seems to be related to animal studies. You shouldn't compare animals with human beings in that regard, because we differ in many regards. The noticeable damage seen on MRI's etc. are probably the effects of neuroplasticity, which works in both ways: creating and "disconnecting" connections between neurons. If you lose a finger for example the brain maps will change and use the free space for other functions(calculation). Even though I don't know pretty much anything about neuroscience, I believe that there might be hyper active areas, which are "forced" to disconnect by said drugs to lessen the symptoms of schizophrenia. Correct me if I am wrong, I am still a noob on here.
 
Hmmmm I wasn't aware that anti-psychotics were actually "neurotoxic", some of the older typicals like Haldol strongly inhibit dopamine sometimes to the point of Parkinsonism and things like this might be harmful to the brain in the sense that your brain might trim neurons that you're not using (plasticity) but other than that things like tardive dyskinesia which at a glance might be thought of as neurotoxicity are very likely a sensitization of dopamine and are not caused by cell death. The older typicals that block dopamine strongly are usually associated with tardive dyskinesia.

The newer atypical antipsychotics that usually antagonize 5-HT2A as well as dopamine have a lot less side effects and you might consider them less toxic. Drugs that inhibit excitatory neurons like 5-HT2A might help reduce excitotoxicity and could be thought of as neuroprotective in that manner (a lot of 5-HT2A connects to glutamate and glutamate is usually concerned when talking about
excitotoxicity).

Sometimes toxicity of a drug is from the metabolism of the drug and not necessarily its intended binding in the brain, don't know if this applies to antipsychotics much.
 
Hmmmm that's very interesting, these studies suggest that the EPS are indeed related to neurotoxicity, it seems to me that it might have something to do with TNFa http://www.ncbi.nlm.nih.gov/m/pubmed/18554768/?i=2&from=/12043843/related
And these EPS/neurotoxicity seem to correlate with the strong dopamine antagonists (the old typicals) while the atypicals are associated with neuroprotective effects and lower risk of EPS. The atypicals also don't antagonize dopamine as strongly, so it must have something to do with dopamine. Maybe dopamine keeps something in check (glutamate?) and without dopamine keeping it in check there is increased excitotoxicity and inflammation. The dopamine projections are pretty important and interact with a lot of other neurotransmitters. However some of these studies were having to do with just cell cultures so I don't know what's causing damage to single cells. I'm hard pressed to believe it's just metabolism.
 
I thought Risperidone was the strongest D2 antagonist of the atypical anti-psychotics and had incidence of EPS pretty much on par with medium potency typical anti-psychotics such as Perphenazine. It has a much higher incidence of EPS then Quetiapine or Olanzapine at doses typically used to treat Bipolar disorder or Schizophrenia. I found that the zombie effect was rather prominent once i got above 2mg's unless i was Manic of course.

I never thought Risperidone or it's active metabolite where Neuroprotective but i had read that strong typical Dopamine antagonists such as Haldol, Zuclopenthixol and others could cause Neurotoxicity.
 
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