Nicotinic receptors are ligand-gated ion channels that are activated by acetylcholine and nicotine. Upon activation, they cause a rapid increase in the permeability of cells to K⁺, Na⁺, and Ca²⁺, followed by depolarization and excitation. They are in the autonomic ganglia, skeletal neuromuscular junction, CNS, and adrenal medulla.

There are two types of nicotinic receptors: neuromuscular (N_M/NM/N₁) and neuronal (N_N/NN/N₂). The two families differ based on their location and selectivity to agonists and antagonists. The neuromuscular junction possesses the N_M type, whereas the CNS, PNS, and non-neuronal tissues have the N_N type. D-tubocurarine, succinylcholine, and decamethonium block the N_M receptors, while trimethaphan and hexamethonium block the N_N receptors.

Nicotinic receptors have pentameric subunits (α, β, γ, ε, and δ) that form a rosette-like receptor complex. N_M receptors have α2, β, γ (or ε), and δ subunits, while N_N receptors have only α or α, β subunits. Each subunit has an intracellular C-terminus, an extracellular N-terminus, and four α helical transmembrane domains around a central pore that serves as the ion channel. On the extracellular domain of the receptors, two acetylcholine binding sites exist at the αγ and αδ interfaces.

Acetylcholine binding to nicotinic receptors causes a change in cell membrane permeability, allowing cation movement through the ion channel. Cation flux depolarizes the end plate, resulting in the contraction of muscles at the neuromuscular junction or nerve impulse continuation at the autonomic ganglia.