Voltage-gated L-type Ca_V1.2 calcium channels couple membrane depolarization to transient increase in cytoplasmic free Ca²⁺ concentration that initiates a number of essential cellular functions including cardiac and vascular muscle contraction, gene expression, neuronal plasticity, and exocytosis¹.

Tricyclic antidepressants (TCAs) are known to inhibit Ca²⁺ currents, including the L-type Ca_V1.2 channel in heart myocyte and neurons². Other known physiological targets of tricyclic antidepressants in the central nervous system are the 5-HT2 serotonin receptors and the α1-adrenergic receptors³.

Amitriptyline hydrochloride, a tricyclic antidepressant, is used for a number of medical conditions including management of depressive, anxiety and bipolar disorders³ and management of chronic pain such as neuropathic pain, diabetic neuropathy, postherpetic neuralgia and fibromyalgia⁴.

The proposed mechanisms of action for amitriptyline hydrochloride include inhibition of the reuptake of serotonin and norepinephrine, inhibition of NMDA receptors, of voltage-gated ion channels such as Ca²⁺ and Na⁺ channels and interaction with adenosine receptors⁵.