Haloperidol: neurotoxic, kills brain cells.

[outriderx]

http://www.jneurosci.org/cgi/content/abstract/27/22/5895

Haloperidol Treatment after High-Dose Methamphetamine Administration Is Excitotoxic to GABA Cells in the Substantia Nigra Pars Reticulata Theo Hatzipetros,1 Jamie G. Raudensky,1 Jean-Jacques Soghomonian,2 and Bryan K. Yamamoto1
1Laboratory of Neurochemistry, Department of Pharmacology and Experimental Therapeutics and 2Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts 02118
Correspondence should be addressed to Bryan K. Yamamoto, Department of Pharmacology, Boston University School of Medicine, 715 Albany Street, L-613, Boston, MA 02118. Email: bkyam@bu.edu
The therapeutic management of methamphetamine (METH)-induced psychoses often involves treatment with the typical antipsychotic drug and dopamine D2 receptor antagonist haloperidol. We report here that subchronic haloperidol administration after a high-dose regimen of METH produces a heretofore unrecognized toxicity to GABAergic cells, as reflected by GAD67 mRNA expression histochemistry, in the rat substantia nigra pars reticulata (SNr) through an acute and persistent augmentation of glutamate release, NMDA receptor activation, and DNA fragmentation. The dopaminergic cells in the substantia nigra pars compacta were unaffected by METH or haloperidol alone or the combination of METH and haloperidol. These findings suggest that the current therapeutic management of METH-induced psychoses with haloperidol may be contraindicated because of a resultant GABAergic cell death in the SNr, which may predispose some individuals to the development of hyperkinetic movement disorders and seizures.

SWIM knew it!!! for SWIM haloperidol always had a touch of toxicity going with it

[Micklemouse]

Yup, it's a dirty drug & no mistake. It does however work, & in cases where rapid tranquilisation is needed has less side effects than some of the alternatives (Chlorpromazine, Clopixol Acuphase) & is often more effective than the current atypical IM medications available for this purpose (i.e. Olanzepine). In the treatment of any psychosis there is always a risk:benefit assessment to be made, & if there is a serious immediate risk to self or others then something has to be done.

Do bear in mind that this study was done on rats, & there is no mention made of data from human studies, probably because there haven't been any.

[radiometer]

What is the definition of "subchronic administration?" I looked for the answer before asking.

[Micklemouse]

Ah, thank you for asking that Radio - I slightly misunderstood the article. Subchronic administration so far as I can tell involves the near constant pumping of a drug into an animal, I'd imagine to simulate the effects of a patient taking a regular dose for a set period of time. In Britain at least psychotic patients are not drip fed or pumped medication in a similar manner to these experiments.

From another study

Subchronic Administration of Antipsychotic Drugs. Doses used in these studies were chosen based on the results of the acute dose-response studies. Osmotic minipumps (model 2 ML4; Alzet, Palo Alto, CA) containing either haloperidol (2.0 mg/kg/day), clozapine (10.0 or 40.0 mg/kg/day), olanzapine (10.0 mg/kg/day), risperidone (1.0, 3.3, or 10.0 mg/kg/day), quetiapine (10.0 or 33.3 mg/kg/day), sertindole (2.0 or 10.0 mg/kg/day), or vehicle were implanted in adult male Sprague-Dawley rats (200-250 g, n = 10 for each group). Fourteen days after the minipumps were implanted, the rats were sacrificed by decapitation, and the brains were rapidly removed and frozen on dry ice. Brains were stored at http://jpet.aspetjournals.org/math/12pt/normal/minus.gif70°C until use.http://jpet.aspetjournals.org/cgi/content/full/295/1/67?ck=nck

Acute administration would be a one off dose with no further medication given.

In the case of an acute psychosis in a human rapid ranquilisation through intramuscular injection is sometimes used to get a decent & lasting dose of medication into the patient in one go. In Britain this is done only in extreme circumstances & unless at the patients request, only when all other methods have failed. It is rare, in A Certain Mouse's experience, that a single dose of medication does the job, even with drug-induced psychoses.

Please remember kittlings, that people on the whole are not rats.

[OccularFantasm]

It should also benoted that intramuscular administration of haloperidol lasts in ones system in significant amounts for a month after administration. Swim could see where such a drug would help quell the symptoms of being high onmeth, but it would seem to swim that the dopamine antagonist effects would exacerbate the withdrawl and after-effects of the meth. Swim also has to agree with the whole toxic dirty drug thing. Swim felt almost all the same effects peopel feel coming off of meth after extended administration of haloperidol, including feeling bugs crawling all over ones skin. If there was a drug whose affinity for hatred was near the infinitive, this would be the drug. It is actually illegal to use haloperidol int he united states to someone under the age of 18 years and whom is not in prison. (If swim sees the doc who put him on it when he was a minor, hes a dead douche)

Oh yeah, and i enojoy how for using the drug it seems it is always forgotten or convienently not mentioned that both extreme excess and extreme depletion of dopamine both cause psychosis. It is especialy interesting, since excess dopamine trips are significantly more enjoyable and less scary than their perscribed counterpart.

And the part of glutamate was interesting to swima s well. Swims levels of glutamate and L-glutamine were basically asasinated after using haloperidol.

Also, if it were ever a question about the pure negative that this drug is, simply read the caution thing that comes with the pills. the list of side effects are uncomparably long. Swim is actualy fairly sure crack would have less things wrong with it to list. My personal favourite was "Unexplained death or coma".