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Expert Rev Neurother. 2018 Feb;18(2):101-110. doi: 10.1080/14737175.2018.1413353. Epub 2017 Dec 15.

Brain circuits and neurochemical systems in essential tremor: insights into current and future pharmacotherapeutic approaches.

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a Department of Neurology , Yale School of Medicine, Yale University , New Haven , CT , USA.
b Department of Chronic Disease Epidemiology , Yale School of Public Health, Yale University , New Haven , CT , USA.
c Center for Neuroepidemiology and Clinical Neurological Research, Yale School of Medicine , Yale University , New Haven , CT , USA.


There are few medications that are available for the treatment of essential tremor (ET) and they are only moderately effective. Areas covered: Data were obtained from a PubMed search. Original articles, review articles, and clinical guidelines were included. Two disease models for ET have been proposed: 1) the olivary model, which attributes ET to a pathological pacemaker in the inferior olivary nucleus, and 2) the cerebellar degeneration model, which postulates that ET originates in the cerebellum and could be related to deficient or abnormal Purkinje cell (PC) output. Underlying biochemical dysfunction in T-type calcium channels (T-tCaC) may loosely be linked to the first model and deficiency/abnormality in γ-aminobutyric acid (GABA) neurotransmission, to the second. Expert commentary: Human data points robustly to the role of GABA in ET. Numerous medications that target the GABA system have been tried, with variable success. Given the many different types of GABA-ergic neurons, and the multitude of GABAA receptor subtypes, a given medication could have competing/cancelling effects. It would seem that influencing GABA receptors broadly is not as effective as targeting certain GABAA receptor subtypes. Future research should seek to identify molecular candidates that have a more targeted effect within the GABA system.


Benzodiazepines; GABA; T-type calcium channel; cerebellum; essential tremor; ethanol; primidone; receptor subunit; topiramate; treatment

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