T-Type Calcium Channel as a New Therapeutic Target for Tremor

Abstract

Voltage-gated calcium channels play an important role in many physiological and pathological processes. Accumulating studies suggest that the T-type calcium channel is a potential target for the treatment of various neurological disorders, such as epilepsy, insomnia, and neuropathic pain. Here, we highlight recent advances in our understanding of T-type calcium channel regulation and their implications for tremor disorders. Several T-type calcium channel blockers effectively suppressed experimental tremors that have been suggested to originate from either the cerebellum or basal ganglia. Among T-type calcium channel blockers that have been used clinically, the anti-tremor efficacy of zonisamide garnered our attention. Based on both basic and clinical studies, the possibility is emerging that T-type calcium channel blockers that transit into the central nervous system may have therapeutic potentials for tremor disorders.

Cannabinoid type 1 receptor antagonism ameliorates harmaline‐induced essential tremor in rat

“…Here, since a severe tremor state was required, upon which only potent ameliorating or exacerbating pharmacological effects of the cannabinoids studied would be revealed, a harmaline dose of 30 mg kg À1 was employed. The primary cause of harmaline-induced tremor is via alteration of synchronous activation of climbing fibres from the inferior olive projecting to cerebellar PC (Kolasiewicz et al, 2009), most likely via repetitive discharge generation in inferior olivary nucleus neurons through potentiation of Ca V 3.1 calcium channels responsible for intrinsic oscillatory activity in this neuronal population (Miwa and Kondo, 2011). One of the most frequently reported effects of cannabis in a survey of MS patients was tremor relief (Koch et al, 2007).…”

Diagnosis and management of essential tremor

“…Нет достаточных доказательств долгосрочной эффективности таламотомии с использованием гамма-ножа. Перспективный нейрохирургический метод -ультразвуковая таламотомия под МРТконтролем [48][49][50]. В целом для определения эффективности и безопасности хирургического лечения ЭТ необходимы дополнительные проспективные контролируемые исследования.…”

Therapeutic advances in tremor

“…Tremor‐related neuronal activities have characteristic repetitive bursting, which is mediated by T‐type channels, highly expressed in the thalamus and inferior olive. Accordingly, both knockdown and knockout of Cav3.1 T‐type channels resulted in suppression of harmaline‐induced tremor in mice . T‐type channel inhibitors currently used as antiepileptic drugs (ethosuximide and zonisamide) and newly discovered drugs, such as (+)‐ECN, ML218, and fluoropiperidine, have exhibited anti‐tremor efficacy in various tremor models, including harmaline‐induced tremor in rodents, gamma aminobutyric acid A a1 subunit knockout mice, 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced parkinsonism in monkeys, and rats with haloperidol‐induced parkinsonism or tacrine‐induced tremulous jaw movements .…”

“…T‐type channel inhibitors currently used as antiepileptic drugs (ethosuximide and zonisamide) and newly discovered drugs, such as (+)‐ECN, ML218, and fluoropiperidine, have exhibited anti‐tremor efficacy in various tremor models, including harmaline‐induced tremor in rodents, gamma aminobutyric acid A a1 subunit knockout mice, 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced parkinsonism in monkeys, and rats with haloperidol‐induced parkinsonism or tacrine‐induced tremulous jaw movements . With the exception of a preliminary experience with zonisamide in ET, no new studies are available, but they are certainly warranted.…”