Minocycline: far beyond an antibiotic

Abstract

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.

Minocycline modulates neuropathic pain behaviour and cortical M1–M2 microglial gene expression in a rat model of depression

“…The antidepressant-like effects of minocycline are proposed to be mediated via attenuation of microglial activation, reduction in pro-inflammatory mediators and neuroprotective mechanisms (Pae et al, 2008, Garrido-Mesa et al, 2013. Several studies from our group and others have demonstrated increased microglial activation, TNFα and/or IL-1β levels in the prefrontal cortex, hippocampus, amygdala and hypothalamus (Borre et al, 2012, Myint et al, 2007, Burke et al, 2013a and neurodegeneration in the amygdala and hippocampus (Wrynn et al, 2000, Jarosik et al, 2007 of OB rats.…”

Impact of Minocycline on Extracellular Matrix Metalloproteinase Inducer, a Factor Implicated in Multiple Sclerosis Immunopathogenesis

“…There are many similarities between the administration of minocycline or anti-EMMPRIN Abs in their ability to modulate T cell activities (1,29,49,50). For example, both minocycline and anti-EMMPRIN Abs reduced T cell proliferation (5,6,12,51,52).…”

“…More recently, a phase III trial in patients with a first demyelinating event (clinically isolated syndrome) found that minocycline reduced the acquisition of a second event to become clinically definite MS (L. M. Metz, D. K. B. Li, A. Traboulsee, P. Duquette, M. Eliasziw, G. Cerchiaro, J. Greenfield, A. Riddehough, M. Yeung, M. Kremenchutzky, et al, submitted for publication). Although minocycline is described to have antiinflammatory, immune-modulatory, and neuroprotective effects (29,30), whether minocycline affects EMMPRIN expression in T cells is unknown.…”

Doxycycline Ameliorates Schizophrenia-Like Behaviors in Experimental Models in Mice by Targeting Underlying Oxidative Stress

“…Hence, the need for newer antipsychotic agents with multipronged mechanisms of action that could target various aspects of the pathologies of schizophrenia has become imperative [7] [8]. To this end, the second-generation tetracycline antibiotic drugs (e.g., minocycline, doxycycline) have recently been attracting much attention in neuropsychiatric preclinical researches due to their antioxidant and anti-inflammatory/immunomodulatory mechanisms of action [9]. Doxycycline is a long acting second-generation tetracycline antibiotic which is rapidly absorbed and penetrates well into the brain, with very low toxicity profile [10].…”

“…Similar to minocycline, doxycycline possesses strong neuroprotective effect and this is closely attributed to its anti-inflammatory, antioxidant, anti-apoptotic and neurotrophic properties [9] [11] [12].…”