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

Lei Tang, Pradeep Kumar Shukla, Zaijie Jim Wang

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1-4
Number of pages4
JournalNeuroscience Letters
Volume397
Issue number1-2
DOIs
StatePublished - Apr 10 2006
Externally publishedYes

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Trifluoperazine
Opioid Analgesics
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Pharmaceutical Preparations
Morphine
Calcium-Calmodulin-Dependent Protein Kinases
Antipsychotic Agents
Up-Regulation
Maintenance

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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Trifluoperazine, an orally available clinically used drug, disrupts opioid antinociceptive tolerance. / Tang, Lei; Shukla, Pradeep Kumar; Wang, Zaijie Jim.

In: Neuroscience Letters, Vol. 397, No. 1-2, 10.04.2006, p. 1-4.

Research output: Contribution to journalArticle

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