Background:

AGN 192403 hydrochloride is a selective ligand of imidazoline1 receptor [1].

Imidazoline receptor is the primary receptor for clonidine and other imidazolines. Imidazoline1 receptor (I1 receptor) lowers blood pressure via inhibition of the sympatho actions by imidazolines.

AGN 192403 hydrochloride is a selective ligand of I1 receptor. AGN192403 exhibited affinity for I1 receptor with Ki value of 42 nM and was only 5-fold less potent than clonidine. However, AGN192403 had no agonist and antagonist activities. In monkey and rat, AGN192403 (5000 μg/kg) had no effect on blood pressure [1]. In astrocytes, AGN 192403 inhibited cytochrome c release, lysosomal acridine orange relocation, caspase-9 activation and decrease in mitochondrial potential, cytotoxicities that was induced by naphthazarin. Also, AGN 192403 inhibited mitochondrial dysfunction and cytotoxicities induced by antimycin A and rotenone, inhibitors of mitochondrial respiration [2]. In isolated normotensive rat hearts, AGN192403 inhibited atrial natriuretic peptide (ANP) release induced by moxonidine (10?6 M) [3].

参考文献:
[1] unk SA1, Lai RK, Burke JE,Munk SA1, Lai RK, Burke JE,Synthesis and pharmacologic evaluation of 2-endo-amino-3-exo-isopropylbicyclo[2.2.1]heptane: a potent imidazoline1 receptor specific agent.Munk et al (1996) Synthesis and pharmacologic evaluation of 2-endo-amino-3-exo-isopropylbicyclo[2.2.1]heptane: a potent imidazoline1 receptor specific agent. J.Med.Chem. 39 1193. PMID: 8632424.Stephen A. Munk,* Ronald K. Lai, James E. Burke, [1].  Munk SA, Lai RK, Burke JE, et al. Synthesis and Pharmacologic Evaluation of 2-endo-Amino-3-exoisopropylbicyclo[2.2.1]heptane: A Potent Imidazoline1 Receptor Specific Agent. J Med Chem, 1996, 39(6): 1193-1195.
[2].  Choi DH, Kim DH, Park YG, et al. Protective effects of rilmenidine and AGN 192403 on oxidative cytotoxicity and mitochondrial inhibitor-induced cytotoxicity in astrocytes. Free Radic Biol Med, 2002, 33(10): 1321-1333.
[3].  Mukaddam-Daher S, Menaouar A, Gutkowska J. Receptors involved in moxonidine-stimulated atrial natriuretic peptide release from isolated normotensive rat hearts. Eur J Pharmacol, 2006, 541(1-2): 73-79.