Minocycline: far beyond an antibiotic

British Journal of Pharmacology - Tập 169 Số 2 - Trang 337-352 - 2013
Natividad Garrido‐Mesa1, Antonio Zarzuelo1, Júlio Gálvez1
1Centro de Investigaciones Biomédicas en Red – Enfermedades Hepáticas y Digestivas (CIBER‐EHD) Department of Pharmacology Center for Biomedical Research University of Granada Granada Spain

Tóm tắt

Minocycline is a second‐generation, semi‐synthetic tetracycline that has been in therapeutic use for over 30 years because of its antibiotic properties against both gram‐positive and gram‐negative bacteria. It is mainly used in the treatment of acne vulgaris and some sexually transmitted diseases. Recently, it has been reported that tetracyclines can exert a variety of biological actions that are independent of their anti‐microbial activity, including anti‐inflammatory and anti‐apoptotic activities, and inhibition of proteolysis, angiogenesis and tumour metastasis. These findings specifically concern to minocycline as it has recently been found to have multiple non‐antibiotic biological effects that are beneficial in experimental models of various diseases with an inflammatory basis, including dermatitis, periodontitis, atherosclerosis and autoimmune disorders such as rheumatoid arthritis and inflammatory bowel disease. Of note, minocycline has also emerged as the most effective tetracycline derivative at providing neuroprotection. This effect has been confirmed in experimental models of ischaemia, traumatic brain injury and neuropathic pain, and of several neurodegenerative conditions including Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Alzheimer's disease, multiple sclerosis and spinal cord injury. Moreover, other pre‐clinical studies have shown its ability to inhibit malignant cell growth and activation and replication of human immunodeficiency virus, and to prevent bone resorption. Considering the above‐mentioned findings, this review will cover the most important topics in the pharmacology of minocycline to date, supporting its evaluation as a new therapeutic approach for many of the diseases described herein.

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Tài liệu tham khảo

10.2174/187152708786441867

10.1093/jac/dkl224

10.1073/pnas.0600554103

10.1016/S0014-5793(97)00605-4

10.1161/CIRCULATIONAHA.108.769331

Aronson AL, 1980, Pharmacotherapeutics of the newer tetracyclines, J Am Vet Med Assoc, 176, 1061

Arsenis C, 1992, Tetracyclines (TETs) inhibit the synthesis and/or activity of cartilage proteinases in vivo and in vitro, Matrix Suppl, 1, 314

10.1001/archderm.137.1.69

10.1016/S8756-3282(97)00104-X

10.1128/AAC.8.6.713

10.1177/0091270010373929

10.1136/jmg.2008.061796

10.1016/j.nbd.2004.07.012

10.2165/00003495-197509040-00005

10.1093/brain/awf133

10.1016/S1734-1140(11)70504-7

10.1371/journal.pone.0018688

10.1016/S0896-6273(03)00501-4

10.1038/77528

10.3340/jkns.2011.49.2.83

10.1038/sj.npp.1301377

10.1006/exnr.1999.7065

10.1016/j.heares.2004.03.012

10.1159/000285514

10.2500/aap.2008.29.3121

10.1002/ana.10818

10.1111/j.0953-816X.2004.03372.x

10.1016/j.expneurol.2004.05.016

10.1016/j.tips.2004.10.001

10.1073/pnas.251341998

10.1111/1523-1747.ep12543487

Esterly NB, 1984, Neutrophil chemotaxis in patients with acne receiving oral tetracycline therapy, Arch Dermatol, 120, 1308, 10.1001/archderm.1984.01650460048018

10.1111/j.1471-4159.2006.03799.x

10.1111/j.1749-6632.1997.tb48428.x

10.1080/13550280802199898

10.1038/40299

10.1016/j.phrs.2010.12.011

10.1016/j.bcp.2011.09.004

Golub L, 1992, Tetracyclines (TCs) inhibit matrix metalloproteinases (MMPs): in vivo effects in arthritic and diabetic rats and new in vitro studies, Matrix Suppl, 1, 315

10.1111/j.1600-0765.1983.tb00388.x

10.1177/10454411910020030201

10.1016/j.archoralbio.2006.10.005

10.1046/j.1365-2133.2003.05497.x

10.1016/S1474-4422(07)70270-3

10.1038/sj.bjp.0706050

Greenwald R, 1993, Tetracyclines in arthritis, J Rheumatol, 20, 1990

10.1016/j.phrs.2011.06.010

Greenwald RA, 1987, Tetracyclines inhibit human synovial collagenase in vivo and in vitro, J Rheumatol, 14, 28

Greenwald RA, 1992, Tetracyclines suppress matrix metalloproteinase activity in adjuvant arthritis and in combination with flurbiprofen, ameliorate bone damage, J Rheumatol, 19, 927

10.1152/ajpcell.00047.2010

10.1523/JNEUROSCI.0003-06.2006

10.1016/S1097-2765(00)00108-8

10.1186/1742-2094-5-15

10.1186/1742-6405-8-17

Holman BL, 1975, Time course of 99mTc(Sn)‐tetracycline uptake in experimental acute myocardial infarction, J Nucl Med, 16, 1144

Holman BL, 1973, Detection and localization of experimental myocardial infarction with 99m Tc‐tetracycline, J Nucl Med, 14, 595

10.1016/j.ejphar.2010.03.059

10.1016/j.ejphar.2011.01.001

10.1007/s00018-011-0763-x

10.1016/j.bbrc.2009.09.041

10.1016/j.taap.2009.02.026

10.1016/0190-9622(91)70255-Z

10.1002/ana.20250

10.1002/glia.20871

10.1128/AAC.01540-08

10.2174/187221311797264919

10.1016/j.phrs.2011.04.001

10.1093/intimm/dxq004

10.2174/156720107781023938

10.1016/j.clim.2004.07.012

10.2353/ajpath.2007.070231

10.1111/j.1600-0757.2006.00166.x

10.1002/(SICI)1097-4652(199605)167:2<359::AID-JCP22>3.0.CO;2-1

10.1016/S0025-7125(16)30039-6

10.1111/j.1749-6632.1994.tb24773.x

10.1111/j.1365-2249.1995.tb03864.x

10.1128/AAC.40.4.934

Koistinaho J, 1997, Altered gene expression in brain ischemia, Neuroreport, 8, i

10.1038/sj.jcbfm.9600040

10.1111/j.1468-3083.2009.03167.x

10.1016/j.brainresrev.2006.06.001

10.2337/diabetes.54.5.1559

10.1002/cpt1978234467

10.1111/j.1471-4159.2005.03219.x

10.1006/nbdi.2002.0487

10.1212/01.wnl.0000277487.04281.db

10.2165/00002018-200022050-00007

10.1016/j.neulet.2011.04.077

10.1016/j.pain.2005.02.009

10.1126/science.288.5464.335

10.4161/auto.7.2.14043

10.1016/j.phrs.2010.11.003

10.1016/j.expneurol.2008.01.022

10.1038/sj.bjp.0706204

10.1016/j.nbd.2006.10.022

10.1016/j.bbi.2011.01.015

10.1016/S0022-5347(17)35268-0

10.1016/j.neures.2011.03.012

10.1002/ana.20111

10.1177/1352458509106779

10.1016/j.ejphar.2007.01.013

10.1177/08959374980120011901

10.1002/ana.10353

10.1111/j.1471-4159.2005.03520.x

10.1074/jbc.M611907200

10.1089/cbr.2008.0475

10.1038/sj.mp.4002148

10.1038/20446

10.1016/j.febslet.2006.06.087

10.1016/j.ejphar.2011.04.014

10.1186/1471-2377-10-91

10.4196/kjpp.2011.15.2.115

10.1146/annurev.genom.8.080706.092249

10.1097/01.MIB.0000225330.38119.c7

10.1097/00005344-200310000-00003

10.1002/ana.10092

10.1016/0006-2952(92)90381-R

10.1124/jpet.103.052407

10.1371/journal.pone.0010523

10.1161/01.STR.29.5.1020

10.1016/j.jacc.2008.06.028

10.1212/WNL.0b013e31822f0412

10.1016/j.neulet.2008.01.041

10.1097/00001813-200311000-00001

10.2165/00003088-198815060-00001

10.1097/00006123-200106000-00051

10.1016/j.jaad.2005.10.004

10.1016/j.jacc.2003.09.050

10.1002/ibd.20377

10.1002/glia.20338

10.1016/j.atherosclerosis.2011.05.041

10.1080/13550280490499533

10.1242/dmm.008045

10.1002/ana.10614

10.2174/1874210600802010005

10.1038/sj.jid.5700965

10.1523/JNEUROSCI.5275-03.2004

10.1177/1073858405275175

Stone M, 2003, Should tetracycline treatment be used more extensively for rheumatoid arthritis? Metaanalysis demonstrates clinical benefit with reduction in disease activity, J Rheumatol, 30, 2112

10.1152/ajprenal.00051.2004

10.1111/j.1600-0765.2005.00843.x

10.1086/651277

10.1097/FJC.0b013e3181faeaf0

10.1016/j.cell.2005.09.007

10.1073/pnas.0306239101

10.2174/1381612043453162

10.1002/mds.20018

10.1523/JNEUROSCI.21-08-02580.2001

10.1093/brain/awf068

10.7326/0003-4819-122-2-199501150-00001

10.1016/j.nbd.2004.01.010

10.1352/1944-7558-115.5.433

10.1097/00001756-200206120-00018

10.1038/sj.bjp.0704966

10.1016/j.neuint.2005.04.018

10.1073/pnas.1832501100

10.1093/brain/awg178

10.1021/bi00267a041

10.3109/10715769709097783

10.1017/S1740925X05000104

10.1016/S0140-6736(74)90941-6

10.1016/S8756-3282(96)00302-X

10.1177/08959374980120012401

10.1523/JNEUROSCI.22-05-01763.2002

10.2353/ajpath.2010.090361

10.1002/jnr.10709

10.1161/01.RES.0000138581.04174.2f

10.1161/01.STR.0000206281.77178.ac

10.1016/S1474-4422(04)00937-8

10.1038/nature01158

10.1073/pnas.95.26.15769

10.1073/pnas.96.23.13496

10.1002/jnr.20289

10.1523/JNEUROSCI.1661-07.2007

10.1177/1352458506070319

10.1097/01.wnf.0000150867.98887.3e

Zernicke RF, 1997, Administration of systemic matrix metalloproteinase inhibitors maintains bone mechanical integrity in adjuvant arthritis, J Rheumatol, 24, 1324

Zhang J, 1994, Changes of monoamines, purines and amino acids in rat striatum as measured by intercerebral microdialysis during ischemia/reperfusion, Chin Med Sci J, 9, 225

10.1038/417074a

10.1186/1756-6606-4-31

10.1001/jama.293.16.2003