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> Trifluoperazine reduces opioid tolerance and dependance
post Feb 22, 2007, 11:43 PM
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Too bad its not a very selective agent and may make you feel tired, drained and crappy due to being a dopamine blocking antipsychotic. The mechanism by interrupting addiction is not dopamine blockade but rather CaMKII Antagonism

Now imagine if you had a drug that did nothing but block CaMKII, a drug that did nothing but block CCK, and DAMGO, and you took those three and added them to Oxycodone or Tramadol's M1 metabolite. You'd have an Opioid pill with 3 known tolerance and dependence blockers added to it.


Trifluoperazine, an orally available clinically used drug, disrupts opioid antinociceptive tolerance.

* Tang L,
* Shukla PK,
* Wang ZJ.

Department of Biopharmaceutical Sciences, College of Pharmacy, University of Illinois, 833 South Woods Street, Chicago, IL 60612, USA.

Calcium/calmodulin dependent protein kinase II (CaMKII) has been shown to play an important role in the generation and maintenance of opioid tolerance. In this study, trifluoperazine was studied for its effect on morphine tolerance in mice. Acute treatment with trifluoperazine (0.5 mg/kg, i.p.) completely reversed the established antinociceptive tolerance to morphine. Pretreatment with trifluoperazine also significantly attenuated the development of antinociceptive tolerance (p<0.01). Morphine induced a significant up-regulation of supraspinal and spinal CaMKII activity in tolerant mice, which was abolished after the pretreatment or acute treatment with trifluoperazine. These data suggested that trifluoperazine was capable of suppressing opioid tolerance, possibly by the mechanism of inhibiting CaMKII. Since trifluoperazine has been safely used as an antipsychotic drug, we propose that the drug should be studied in humans for the prevention and treatment of opioid tolerance and addiction.


Antipsychotic Drug May Block Addiction, Researchers Find

Science Daily — Researchers at the University of Illinois at Chicago have discovered that a long-approved oral antipsychotic drug can stop the addictive properties of opioid painkillers in mice.

The researchers injected a small dose (half a milligram) of trifluoperazine -- used in the treatment of mental diseases such as schizophrenia -- into laboratory mice hooked on morphine. After a few hours their addiction was gone, said Z. Jim Wang, assistant professor of pharmacology in the UIC College of Pharmacy.

This is the first time any study has shown the anti-addictive property of trifluoperazine, Wang said.

"From studies conducted in the 1970s and 1980s, we know that trifluoperazine inhibits calmodulin," Wang said, a molecule that is required for the activation of an enzyme called calcium/calmodulin-dependent protein kinase-2. "In previous studies we performed at UIC, we know that CaMK-2 plays an important role in the generation and maintenance of opioid tolerance," he said. Tolerance is a hallmark of drug dependence.

"Trifluoperazine targets this pathway, which then stops the addiction," Wang said. "When this occurs, you can still use a relatively low dose of the painkiller to achieve fairly good pain control and no drug dependence."

Opioids such as morphine are commonly used in pain management, but many patients are wary of taking them because of concerns over addiction or adverse side effects.

The study, which began early last year and was supported in part by grants from the National Institutes of Health and the American Foundation for Pharmaceutical Education, is published in the journal Neuroscience Letters. It is now available online and will be printed later this month.

Other researchers involved in the study were graduate student Lei Tang and post-doctoral researcher Pradeep Shukla, both of the UIC College of Pharmacy.

Note: This story has been adapted from a news release issued by University of Illinois at Chicago.
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post Jul 14, 2007, 08:27 PM
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Rimbonant produces a similiar effect.
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