The effects of a novel histamine-3 receptor inverse agonist on essential tremor in comparison to stable levels of alcohol

R. W.M. Zoethout, R. Iannone, B. R. Bloem, J. Palcza, G. Murphy, J. Chodakewitz, A. Buntinx, K. Gottesdiener, S. Marsilio, L. Rosen, K. Van Dyck, E. D. Louis, A. F. Cohen, R. C. Schoemaker, S. Tokita, N. Sato, K. S. Koblan, R. H. Hargreaves, J. J. Renger, J. M.A. Van Gerven

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Essential tremor (ET) is a common movement disorder. Animal studies show that histaminergic modulation may affect the pathological processes involved in the generation of ET. Histamine-3 receptor inverse agonists (H3RIA) have demonstrated attenuating effects on ET in the harmaline rat model. In this double-blind, three-way cross-over, single-dose, double-dummy study the effects of 25 mg of a novel H3RIA (MK-0249) and a stable alcohol level (0.6 g L -1) were compared with placebo, in 18 patients with ET. Tremor was evaluated using laboratory tremorography, portable tremorography and a clinical rating scale. The Leeds Sleep Evaluation Questionnaire (LSEQ) and a choice reaction time (CRT) test were performed to evaluate potential effects on sleep and attention, respectively. A steady state of alcohol significantly diminished tremor as assessed by laboratory tremorography, portable tremorography and clinical ratings compared with placebo. A high single MK-0249 dose was not effective in reducing tremor, but caused significant effects on the LSEQ and the CRT test. These results suggest that treatment with a single dose of MK-0249 does not improve tremor in alcohol-responsive patients with ET, whereas stable levels of alcohol as a positive control reproduced the commonly reported tremor-diminishing effects of alcohol.

Original languageEnglish (US)
Pages (from-to)292-302
Number of pages11
JournalJournal of Psychopharmacology
Volume26
Issue number2
DOIs
StatePublished - Feb 1 2012
Externally publishedYes

Keywords

  • Alcohol
  • clamp
  • essential tremor
  • histamine
  • inverse agonist

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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    Zoethout, R. W. M., Iannone, R., Bloem, B. R., Palcza, J., Murphy, G., Chodakewitz, J., Buntinx, A., Gottesdiener, K., Marsilio, S., Rosen, L., Van Dyck, K., Louis, E. D., Cohen, A. F., Schoemaker, R. C., Tokita, S., Sato, N., Koblan, K. S., Hargreaves, R. H., Renger, J. J., & Van Gerven, J. M. A. (2012). The effects of a novel histamine-3 receptor inverse agonist on essential tremor in comparison to stable levels of alcohol. Journal of Psychopharmacology, 26(2), 292-302. https://doi.org/10.1177/0269881111398685