Rilmenidine is a centrally acting antihypertensive agent that has been shown to lower arterial pressure in various animal models by inhibiting the tonic activity of sympathoexcitatory neurons in the rostral ventrolateral medulla. Rilmenidine targets the nonadrenergic imidazoline-binding site I1 receptor with a Ki value of 7.1 nM and demonstrates weaker affinity for the I2 receptor with a Ki value of 5.2 μM. It can also act as an agonist of α2-adrenergic receptors, but demonstrates ~30-fold greater selectivity for I1 receptors compared to α2-adrenergic receptors. Rilmenidine is reported to induce autophagy as evidenced by a ~350% increase in LC3-II levels in PC12 cells when treated with 1 μM of the I1 agonist.
