Rilmenidine is an 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 [1].

In vitro: Bilateral microinjection of rilmenidine into the C1 area of the rostral ventrolateral medulla (RVL) elicited dose-dependent falls in arterial pressure and heart rate. In RVL, rilmenidine competed with binding to imidazole and α2-adrenergic binding sites with a 30-fold selectivity for the imidazole binding sites [2]. Rilmenidine, a new antihypertensive agent, appeared 2.5 and 3.5 times more selective than clonidine and guanfacine, respectively, for medullary IPR sites than for cortical α-adrenoceptors [3]. Rilmenidine targeted the nonadrenergic imidazoline-binding site I1 receptor with the Ki value of 7.1 nM and demonstrated weaker affinity for the I2 receptor with the Ki value of 5.2 μM [4].

In vivo: In rat model of hypertension associated with insulin resistance, rilmenidine ameliorated the deleterious effects of a high-fructose diet, such as weight gain, hypertension, and resistance to the effects of insulin [5]. In a mouse model of Huntington's disease, rilmenidine induced autophagy, attenuated toxicity of polyglutamine expansions and the signs of disease, reduced the mutant huntingtin fragment levels [6].

References:
[1] Reis, D. J. and Piletz, J.E. The imidazoline receptor in control of blood pressure by clonidine and allied drugs. American Journal of Physiology 273(5 Pt 2), R1569-R1571 (1997).
[2] Gomez R E, Ernsberger P, Feinland G, et al.  Rilmenidine lowers arterial pressure via imidazole receptors in brainstem C1 area[J]. European journal of pharmacology, 1991, 195(2): 181-191.
[3] Bricca G, Dontenwill M, Molines A, et al.  Rilmenidine selectivity for imidazoline receptors in human brain[J]. European journal of pharmacology, 1989, 163(2): 373-377.
[4] Guyenet P G.  Is the hypotensive effect of clonidine and related drugs due to imidazoline binding sites [J]. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 1997, 273(5): R1580-R1584.
[5] Penicaud L, Berthault M F, Morin J, et al.  Rilmenidine normalizes fructose-induced insulin resistance and hypertension in rats[J]. Journal of hypertension. Supplement: official journal of the International Society of Hypertension, 1998, 16(3): S45-9.
[6] Rose C, Menzies F M, Renna M, et al.  Rilmenidine attenuates toxicity of polyglutamine expansions in a mouse model of Huntington's disease[J]. Human molecular genetics, 2010, 19(11): 2144-2153.