Essential tremor (ET) is one of the most common and most disabling movement disorders among adults. The drug treatment of ET remains unsatisfactory. Additional therapies are required for patients with inadequate response or intolerable side effects. The current study aims to investigate the anti-tremogenic and neuroprotective effects of memantine (NMDA receptor antagonist) on the harmaline model of transient action tremor. The effects of memantine were further compared with ethanol. Three separate groups of male Wistar rats were injected either with saline, ethanol (1.5 gr/kg), or memantine (5 mg/kg) 15 min prior to a single intraperitoneal injection of harmaline (20 mg/kg). Tremor and locomotion were evaluated by a custom-built tremor and locomotion analysis system. After 24 h of harmaline injection, cellular viability, and apoptosis were assessed using crystal violet staining, and caspase-3 immunostaining, respectively. Harmaline caused neuronal cell loss and caspase-3 mediated apoptosis in cerebellar granular and purkinje cells as well as the inferior olivary neurons. Despite a reduction in tremor intensity and duration with ethanol, this compound resulted in cell loss in cerebellum and olivary nucleus. Memantine exhibited neuroprotective efficacy on cerebellar and inferior olivary neurons albeit weaker anti-tremor effect compared to ethanol. In conclusion, anti-tremogenic and neuroprotective effects do not necessarily overlap. Memantine is a potential treatment for ET particularly given its neuroprotective efficacy. (C) 2011 Elsevier Ltd. All rights reserved.