生物活性

• 靶点	Calcium Channel IC50:2.6nM

• 描述Manidipine (Dihydrochloride) is a lipophilic, third-generation, highly vasoselective, dihydropyridine (DHP) calcium channel antagonist, which, when given on a once-daily basis, effectively reduces blood pressure (BP) in patients with mild-to-moderate essential hypertension. Diabetic patients and very elderly patients with mild-to-moderate hypertension also respond favourably to treatment with manidipine^[3]. Manidipine shows long-lasting calcium channel-blocking action in vascular smooth muscle cells and antihypertensive actions in various types of hypertensive models. The drug has high selectivity for resistance vessels, dilates renal vasculature, and inhibits renal vascular constrictions induced by norepinephrine and angiotensin II in spontaneously hypertensive rats. It increases renal blood flow and has a prominent natriuretic action without changing glomerular filtration rate. Furthermore, manidipine prevents the development of cerebrovascular lesions and inhibits the progression of vascular damage in the brain and kidneys of stroke-prone spontaneously hypertensive rats. The drug also inhibits a proliferative response of the intima to balloon catheter-induced injury in the carotid arteries of spontaneously diabetic rats without affecting plasma lipids or blood pressure^[4]. In human macrophages THP-1, treatment with different cytokines was able to stimulate by about 3-folds the release of IL-6 (interleukin-6) and Manidipine 1 microM showed a 25% inhibition on TNF-alpha-induced IL-6 secretion. In these cells, a combined treatment with multiple cytokines, induced IL-6 production of about 6-folds and Manidipine was able to reduce such inflammatory response by 30%^[5]. Manidipine plus delapril is a fixed-dose combination of a third-generation dihydropyridine calcium antagonist and an angiotensin-converting enzyme inhibitor, which is effective in mild-to-moderately hypertensive patients with an inadequate response to monotherapy^[6]. The antiviral activity of MND (Manidipine Dihydrochloride) is specific for HCMV (human cytomegalovirus) over different both DNA and RNA viruses. Further experiments in HCMV-infected cells testing the effects of MND on viral DNA synthesis and viral proteins expression revealed that it halts the progression of the virus cycle prior to viral DNA replication and E genes expression, but after IE proteins expression^[7].
• 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
  NCT00157586	Type 2 Diabetes	Phase 3	Completed	-	Italy ... more >> ASL of Ponte San Pietro - Diabetologic Unit Ponte San Pietro, Bergamo, Italy, 24036 Clinical Research Center for Rare Diseases Ranica, Bergamo, Italy, 24020 Hospital of Romano di Lombardia - Diabetologic Unit Romano di Lombardia, Bergamo, Italy, 24058 Hospital " Bolognini " - Medicine Unit Seriate, Bergamo, Italy, 24068 Hospital " Treviglio Caravaggio" - Diabetologic Unit Treviglio, Bergamo, Italy, 24128 Humanitas Institute - Endocrinology and Diabetologic Unit Rozzano, Milano, Italy, 20089 Hospital "Ospedali Riuniti di Bergamo" - Diabetologic Unit Bergamo, Italy, 24128 Slovenia Department of Endocrinolgy, Diabetes and Metabolic Disease - University Medical Center Lubiana, Slovenia Collapse <<
  NCT03106597	Hypertension	Phase 4	Recruiting	December 10, 2018	Korea, Republic of ... more >> Yonsei University Severance Hospital Recruiting Seoul, Korea, Republic of, 03722 Contact: Sang Hak Lee, MD, PhD    82-10-5472-6911    shl1106@yuhs.ac    Sub-Investigator: Sang Hak Lee, MD, PhD          Korea University Guro Hospital Recruiting Seoul, Korea, Republic of, 08308 Contact: Seung-hoe Song, MBE    82-2-2626-1635    ssessong@korea.ac.kr    Contact: Da-in Lee    82-2-2626-2279    0124dain@gmail.com    Yonsei University Wonju Hospital Recruiting Wonju, Korea, Republic of, 26426 Contact: Jang Young Kim, PhD          Contact    82-10-5360-0463    kimjy@yonsei.ac.kr    Sub-Investigator: Jang Young Kim, PhD Collapse <<
  NCT00741585	Essential Hypertension ... more >> Cardiovascular Disease Stroke Chronic Kidney Disease Collapse <<	Phase 4	Completed	-	Spain ... more >> CS Friol Friol, Lugo, Spain, 27220 CS Baiona Baiona, Pontevedra, Spain, 36300 CS Bueu Bueu, Pontevedra, Spain, 36930 CS A Estrada La Estrada, Pontevedra, Spain, 26680 CS A Guarda La Guardia, Pontevedra, Spain, 36780 CS Valmiñor Nigran, Pontevedra, Spain, 36250 CS Panxón Nigrán, Pontevedra, Spain, 36340 CS Tomiño Tomiño, Pontevedra, Spain, 36200 Bioengineering & Chronobilogy Labs., University of Vigo Vigo, Pontevedra, Spain, 36200 Hospital do Meixoeiro Vigo, Pontevedra, Spain, 36200 CS Calle Cuba Vigo, Pontevedra, Spain, 36202 CS A Doblada Vigo, Pontevedra, Spain, 36205 CS Coia Vigo, Pontevedra, Spain, 36209 CS Sardoma Vigo, Pontevedra, Spain, 36214 CS Teis Vigo, Pontevedra, Spain, 36216 CS Vilaboa Vilaboa, Pontevedra, Spain, 36141 CS San Roque Vilagarcía De Arousa, Pontevedra, Spain, 36600 CS Fingoi Lugo, Spain, 27002 Complexo Hospitalario Universitario de Ourense Orense, Spain, 32005 CS Lerez Pontevedra, Spain, 36156 Collapse <<

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• 参考文献

• [1] Tohse N, Takeda Y, Kanno M. Voltage-dependent modulation of L-type Ca2+ current by manidipine in guinea-pig heart cells. Eur J Pharmacol. 1993 Nov 9;249(2):231-3.

  [2] Pfaffendorf M, Mathy MJ, van Zwieten PA. Effects of manidipine and other calcium antagonists on rat renal arcuate arteries. Am Heart J. 1993 Feb;125(2 Pt 2):571-7.

  [3] Roca-Cusachs A, Triposkiadis F. Antihypertensive effect of manidipine. Drugs. 2005; 65 Suppl 2:11‐19

  [4] Nagaoka A. Pharmacologic characteristics of a new calcium antagonist, manidipine: beneficial effects on renal circulation and vascular changes. Am Heart J. 1993; 125(2 Pt 2):560‐565

  [5] Costa S, Zimetti F, Pedrelli M, Cremonesi G, Bernini F. Manidipine reduces pro-inflammatory cytokines secretion in human endothelial cells and macrophages. Pharmacol Res. 2010; 62(3):265‐270

  [6] Coca A. Manidipine plus delapril in patients with Type 2 diabetes and hypertension: reducing cardiovascular risk and end-organ damage. Expert Rev Cardiovasc Ther. 2007; 5(2):147‐159

  [7] Mercorelli B, Luganini A, Celegato M, Palù G, Gribaudo G, Loregian A. Repurposing the clinically approved calcium antagonist manidipine dihydrochloride as a new early inhibitor of human cytomegalovirus targeting the Immediate-Early 2 (IE2) protein. Antiviral Res. 2018; 150:130‐136

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