Modulators of voltage-dependent calcium channels for the treatment of nervous system diseases

Voltage-dependent Ca²⁺ channels (VDCCs) play important roles in physiological functions and pathological processes of the nervous system. Given that the precise regulation of Ca²⁺ signaling is important for neuronal processes such as action potential generation, transmitter release, and synaptic plasticity, alterations in Ca²⁺ current through VDCCs affect the functions of neurons and circuits. Central nervous system (CNS) diseases, including pain, epilepsy, seizure, anxiety, depression, dementia, and stroke, are characterized by an altered balance between excitatory and inhibitory neuronal functions. An efficient way of controlling such diseases is to block or modulate VDCC function. An effective strategy to reduce the likelihood of adverse effects is to develop agents that selectively control the VDCC isoform/subunit involved in the mechanism of the disease in question. This review provides an overview of knowledge on VDCCs, traditional and newly developed therapeutic fields, clinical fields, and the diverse medicinal chemistry of traditional and newly developed VDCC blockers in the CNS based on the scientific and patent literature.