• Eur. J. Pharmacol. · Jan 2014

    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, and Zaijie J Wang.
    • University of Illinois at Chicago, College of Medicine, Division of Hematology/Oncology, Chicago, IL, USA; Jesse Brown Veteran's Administration Medical Center, Chicago, IL, USA; University of Illinois at Chicago College of Pharmacy Department of Biopharmaceutical Sciences, Chicago, IL, USA; Comprehensive Sickle Cell Center, University of Illinois Hospital and Health Sciences System, Chicago, IL, USA. Electronic address: remoloki@uic.edu.
    • Eur. J. Pharmacol. 2014 Jan 15;723:419-24.

    AbstractRecent evidence of neuropathic pain among adults with sickle cell disease (SCD) reveals a need for adjuvant analgesic treatments for these patients. Ca(2+)/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, 10mg), 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 10mg doses, respectively. Eight subjects reported 50% reduction in chronic pain without severe sedation or supplemental opioid analgesics; one of these subjects had dystonia 24.5h after the 10mg dose. The analgesic effect lasted for at least 24h in 3 subjects. Sedation resolved with caffeine and dystonia resolved with diphenhydramine. Adults with SCD experienced minimal adverse effects at doses under 10mg. 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 1mg in repeated doses to determine long-term adverse and analgesic effects.© 2013 Published by Elsevier B.V.

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