生物活性

• 描述α2-Adrenoceptors (α2-AR) found in the cardiomyocyte's sarcolemma represent a very important negative feedback for control of myocardial contractility by endogenous catecholamines^[2]. Rilmenidine is a clinically approved anti-hypertensive agent that acts by activating ADRA2/α2-adrenoceptors and imidazoline-1 receptors (I₁Rs) in the brain and periphery. It can be a mTOR-independent autophagy inducers. Stable inducible PC12 cells expressing either wild-type (23Q) or expanded polyglutamine (74Q) huntingtin both showed a significant increase in LC3-II (microtubule-associated protein 1 light chain) when treated with rilmenidine for 24 h^[3]. Sinus rate, corrected sinus recovery time (CSRT) and Wenckebach point (WP) were measured in seven intact dogs. Atrial rate and atrial effective refractory period (AERP) were measured in six atrioventricular (AV)-blocked dogs with ventricular pacing. Each dog received with at least a three-day interval rilmenidine as dihydrogen phosphate in four successive intravenous injections, 30 min apart. In intact dogs, rilmenidine was administered at 50, 50, 100 and 200 μg/kg. In AV-blocked dogs, doses of rilmenidine were 25, 25, 50 and 100 μg/kg. Rilmenidine decreased sinus rate and atrial rate from the first dose. A lengthening of CSRT and a lowering of WP were observed at all doses with rilmenidine. A shortening of AERP was also seen with rilmenidine from the second dose^[4].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02539810	Hypertension ... more >>Hypertension Resistant to Conventional Therapy Angiographically Proven Grade III Unilateral or Bilateral Atherosclerotic Renal Artery Stenosis (ARAS) Greater Than or Equal to 60 Percent Collapse <<	Phase 4	Terminated	-	France ... more >> Hopital Pasteur Nice, Alpes-Maritimes, France, 06002 Hopital Saint Andre - CHU Bordeaux Bordeaux, Gironde, France, 33075 Hopital Rangueil - CHU Toulouse Toulouse, Haute-Garonne, France, 31059 Hopital Lapeyronie - CHU Montpellier Montpellier, Herault, France, 34295 Hopital Arthur Gardiner Dinard, Ille-et-Vilaine, France, 35800 Hopital Pontchaillou - CHU Rennes Rennes, Ille-et-Vilaine, France, 35033 Groupe Hospitalier Mutualiste Grenoble, Isere, France, 38028 Hopital Michallon - CHU Grenoble La Tronche, Isere, France, 38700 Institut Lorrain du Cœur et des Vaisseaux Louis Mathieu Vandoeuvre les Nancy, Meurthe-et-Moselle, France, 54500 Hopital de Brabois Vandoeuvre les Nancy, Meurthe-et-Moselle, France, 54511 Hopital Cardiologique - CHRU Lille Lille, Nord, France, 59037 CHU Clermont-Ferrand Clermont-Ferrand, Puy-de-Dome, France, 63000 Hopital de la Croix-Rousse - CHU Lyon Lyon, Rhone, France, 69004 Hopital de la Pitie Salpetriere Paris, France, 75013 Hopital Europeen Georges Pompidou (HEGP) Paris, France, 75015 Collapse <<
  NCT00892892	Chronic Kidney Disease ... more >> Hypertension Collapse <<	Phase 4	Withdrawn	-	Germany ... more >> University of Erlangen-Nuremberg, CRC, med. Clinic 4 Erlangen, Bavaria, Germany, 91054 Collapse <<

• 参考文献

• [1] Tonet J, Guillet C, et al. Electrophysiological effects of intravenous rilmenidine in man. Eur J Clin Pharmacol. 1991;41(6):537-40.

  [2] Maltsev AV, Evdokimovskii EV, Kokoz YM. α2-Adrenoceptor signaling in cardiomyocytes of spontaneously hypertensive rats starts to impair already at early age. Biochem Biophys Res Commun. 2019;512(4):908-913.

  [3] Rose C, Menzies FM, Renna M, et al. Rilmenidine attenuates toxicity of polyglutamine expansions in a mouse model of Huntington's disease. Hum Mol Genet. 2010;19(11):2144-2153.

  [4] Boucher M, Dubar M, Chassaing C, Vivet P, Duchêne-Marullaz P. Cardiac electrophysiological effects of rilmenidine, a novel antihypertensive agent, in the conscious dog: comparison with clonidine. Life Sci. 1994;54(22):PL381-PL387.