Essential Tremor: What We Can Learn from Current Pharmacotherapy

Area of Science:

• Neuroscience
• Pharmacology

Background:

• Essential tremor (ET) pathophysiology, particularly at the cellular level, remains poorly understood.
• While no ET-specific drugs exist, various medications influence tremor severity, offering insights into underlying mechanisms.
• Studying drug mechanisms can illuminate ET pathophysiology and inform rational drug design.

Purpose of the Study:

• To review the mechanisms of action of medications that mitigate essential tremor.
• To correlate drug mechanisms with tremor improvement or worsening.
• To identify potential therapeutic targets for essential tremor.

Main Methods:

• Literature review focused on the mechanisms of action of tremor-mitigating medications.

Main Results:

• Medications increasing gamma-aminobutyric acid (GABA)-A receptor opening duration are consistently linked to tremor improvement.
• Drugs increasing GABA availability did not correlate with tremor improvement.
• Other potential mechanisms include alpha-2 delta calcium channel subunit antagonism, carbonic anhydrase inhibition, and synaptic vesicle protein 2A inhibition.
• Beta-adrenergic blockers with B2 affinity, lacking sympathomimetic and membrane-stabilizing properties, and with CNS penetration may be beneficial.

Conclusions:

• Current understanding of ET cellular physiology relies heavily on serendipitous drug observations.
• Further investigation into currently available agents, based on drug similarities and rational inferences, is warranted for ET clinical trials.