Mechanism-driven phase i translational study of trifluoperazine in adults with sickle cell disease

Robert E. Molokie, Diana J. Wilkie, Harriett Wittert, Marie L. Suarez, Yingwei Yao, Zhongsheng Zhao, Ying He, Zaijie J. Wang

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Recent evidence of neuropathic pain among adults with sickle cell disease (SCD) reveals a need for adjuvant analgesic treatments for these patients. Ca2+/calmodulin protein kinase IIα (CaMKIIα) has a known role in neuropathic pain and trifluoperazine is a potent CaMKIIα inhibitor. The study aim was to determine trifluoperazine's acute effects, primarily on adverse effects and secondarily on pain intensity reduction, in adults with SCD. In a phase I, open-label study of 6 doses of trifluoperazine (0.5, 1, 2, 5, 7.5, 10 mg), we obtained 7-hourly and 24-h repeated measures of adverse effects, pain intensity, and supplemental opioid analgesics in 18 adults with SCD (18 hemoglobin SS disease, 15 women, average age 35.8±8.9 years, ranged 23-53) each of whom received a single dose. Data were analyzed with descriptive statistics. Subjects reported moderate to severe sedative effects at 7.5 and 10 mg doses, respectively. Eight subjects reported 50% reduction in chronic pain without severe sedation or supplemental opioid analgesics; one of these subjects had dystonia 24.5 h after the 10 mg dose. The analgesic effect lasted for at least 24 h in 3 subjects. Sedation resolved with caffeine and dystonia resolved with diphenhydramine. Adults with SCD experienced minimal adverse effects at doses under 10 mg. In this molecular mechanism-driven translational study, trifluoperazine shows promise as an analgesic drug that is worthy of further testing in a randomized controlled study of adults with SCD starting at a dose of 1 mg in repeated doses to determine long-term adverse and analgesic effects.

Original languageEnglish
Pages (from-to)419-424
Number of pages6
JournalEuropean Journal of Pharmacology
Issue number1
StatePublished - 15 Jan 2014
Externally publishedYes


  • Neuropathic pain
  • Phase 1 study
  • Safety
  • Sickle cell disease
  • Trifluoperazine


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