Harmaline Tremor: Underlying Mechanisms in a Potential Animal Model of Essential Tremor

摘要: Background: Harmaline and harmine are tremorigenic b-carbolines that, on administration to experimental animals, induce an acute postural kinetic tremor of axial truncal musculature. This drug-induced action has been proposed as a model essential tremor. Here we review what is known about harmaline Methods: Using the terms PubMed, searched for papers describing effects these mammalian tissue, or humans. Results: Investigations over four decades have shown that induces rhythmic burst-firing activity in medial dorsal accessory inferior olivary nuclei transmitted via climbing fibers Purkinje cells deep cerebellar nuclei, then brainstem spinal cord motoneurons. The critical structures required expression olive, fibers, nuclei; not required. Enhanced synaptic norepinephrine blockade ionic glutamate receptors suppresses tremor, whereas enhanced serotonin exacerbates Benzodiazepines muscimol suppress Alcohol but harmaline-associated neural damage. Recent investigations mechanism focused T-type calcium channel. Discussion: Like involves cerebellum, classic medications found leading utilization preclinical testing antitremor drugs. Limitations acute, unlike only approximately half drugs reported subsequently clinical trials.