Yasinalli Tamboli, Laurent Ferron, Gerald W. Zamponi
INTRODUCTION: T-type calcium channels are critical for a number of physiological and pathophysiological processes and are potential molecular targets for antiepileptics, analgesics, and drugs that alleviate essential tremor. There have been extensive efforts in identifying and developing novel small organic compounds that block the activities of T-type calcium channels. This is reflected in a number of patent applications and issued patents that cover such molecules. AREAS COVERED: Literature and patent databases (PubMed, Scopus, WoS, USPTO, EPO, SciFinder, Lens, Patentscope, Google Patents, Freepatentsonline) were searched from 2018 to 2025. This review updates the landscape of T-type calcium channel blockers focusing on patented organic small molecules categorized by chemical scaffold. EXPERT OPINION: Multiple molecules that target T-type calcium channels have been tested in preclinical models, and some have recently advanced into the clinic. Adverse effects of pan‑T-type calcium channel blockers that have been reported in clinical trials for essential tremors may perhaps be avoided by the development of T-type channel subtype-specific inhibitors.