A Potential New Treatment for Essential Tremor
Octanol has advantages over ethanol as a treatment, but long-term study is needed.
Octanol, a naturally occurring 8-carbon alcohol approved by the FDA as a food additive, has been shown to inhibit calcium channels on inferior-olive neurons in the medulla, thereby reducing these neurons' synchronized intrinsic oscillations and reducing drug-induced tremor in a rat model. Ethanol has similar effects on drug-induced tremor and is known to reduce essential familial tremor (EFT) in humans. In a randomized, placebo-controlled trial, Bushara and colleagues showed that a single 1-mg/kg oral dose of 1-octanol decreased tremor amplitude for up to 90 minutes in 12 patients with EFT without resulting in serious side effects or signs of intoxication (Neurology 2004; 62:122). Now, the same group reports the results of an open-label, dose-escalation study in 20 patients with mild-to-moderate ethanol-responsive EFT.
Single oral doses as high as 64 mg/kg were well tolerated and produced significant tremor reduction, with maximal reduction at 2 hours, without obvious intoxication or other side effects except for an unusual taste reported by four patients. Tremor was measured by accelerometry, spiral drawing, and handwriting. Serum levels of 1-octanol could not be measured. Patients' reports of functional improvement were not recorded. The authors conclude that 1-octanol is a promising treatment for EFT and recommend larger efficacy trials.
Comment: Although ethanol is inexpensive, readily available in various beverages, and highly effective against EFT in doses that are not intoxicating, it is rejected by certain patients, should not be recommended to children or to people who work in certain situations (such as those in which performance might be reduced by alcohol consumption), and is not suitable for chronic antitremor therapy. Thus, an alternative medication would be welcome, and 1-octanol looks promising, at least in a single-dose setting. Only a long-term study will tell how octanol matches up against propranolol, primidone, and gabapentin, all of which are reportedly effective as chronic therapies for EFT. Finding the naturally occurring ligand that is presumed to be active at alcohol-sensitive receptors might also result in a useful new medical therapy for EFT.
Robert R. Young, MD
Dr. Young is Professor of Neurology, Keck School of Medicine, University of Southern California, Los Angeles.
Published in Journal Watch Neurology September 23, 2004
Shill HA et al. Open-label dose-escalation study of oral 1-octanol in patients with essential tremor. Neurology 2004 Jun 22; 62:2320-2.
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