Native voltage-gated Ca²⁺ channels (VGCC, Ca_V) are pharmacologically classified into at least five different subclasses (L-, N-, P-, Q-, and R-type), the characteristics of which are determined by the pore-forming α1 subunit. The subunits Ca_V1.1-1.4 (α_1S, α_1C, α_1D and α_1F) form L-type Ca²⁺ channels and bind dihydropyridines (DHPs) with high affinity^1-3. Nimodipine is a strongly selective L-type Ca²⁺ channel blocker, with IC₅₀ of 139 nM for Ca_V1.2 channel currents in Xenopus oocytes⁴. At 1 µm, Nimodipine inhibits 90% of the Ca_V1.2 channel current at voltages between -20 and +40 mV⁴.

Ca²⁺ antagonists block Ca²⁺ entry into cells, resulting in relaxation of smooth muscle and limitation of the cytotoxic effects of ischaemia in various organ systems. They are most frequently used for clinical conditions requiring vasodilatation, i.e. hypertension and Raynaud's phenomenon. Other uses include treatment of supraventricular arrhythmias and angina. Nimodipine has been approved for treating vasospasm after subarachnoid haemorrhage⁵.

Cytosolic free Ca²⁺ increases with ageing and since this increase may be mediated by the voltage operated L-type Ca²⁺ channel on the neuronal cell body, chronic treatment with an L-channel blocker, like Nimodipine, might palliate the progression of and possibly prevent the majority of cases of Alzheimer’s disease⁶.

A migraine attack is initiated by a cellular hypoxia that can cause an increase in the flow of calcium into the intracellular space, resulting in calcium overload and cellular dysfunction. Nimodipine exhibits selective effects on cerebral vessels and seems to offer protection against the cerebral ischemia and hypoxia presumed to be operative during migraine attacks and indeed, the frequency and duration of migraine attacks are decreased by at least half in 69% of patients treated with this agent⁷.