|Trade names||Minocin, Minomycin, Akamin, others|
|Oral, intravenous, topical|
|Elimination half-life||11–22 hours|
|Excretion||mostly fecal, rest renal|
|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||457.483 g·mol−1|
|3D model (JSmol)|
|(what is this?)|
Minocycline, sold under the brand name Minocin among others, is a tetracycline antibiotic used to treat a number of bacterial infections such as pneumonia. It is generally less preferred than the tetracycline doxycycline. It is also used for the treatment of acne and rheumatoid arthritis. It is taken by mouth.
Common side effects include nausea, diarrhea, dizziness, allergic reactions, and kidney problems. Serious side effects may include anaphylaxis, a lupus-like syndrome, and easy sunburning. Use in the later part of pregnancy may harm the baby and safety during breastfeeding is unclear. It works by decreasing a bacteria's ability to make protein thus stopping its growth.
Minocycline was patented in 1961 and came into commercial use in 1971. It is available as a generic medication. A month supply in the United Kingdom costs the NHS about 14 £ as of 2019. In the United States the wholesale cost of this amount is about US$12. In 2016 it was the 229th most prescribed medication in the United States with more than 2 million prescriptions.
Minocycline and doxycycline are frequently used for the treatment of acne vulgaris. Both of these closely related antibiotics have similar levels of efficacy, although doxycycline has a slightly lower risk of adverse side effects. Historically, minocycline has been an effective treatment for acne vulgaris. However, acne that is caused by antibiotic-resistant bacteria is a growing problem in many countries. In Europe and North America, a number of people with acne no longer respond well to treatment with tetracycline family antibiotics because their acne symptoms are caused by bacteria (primarily Cutibacterium acnes) that are resistant to these antibiotics. In order to reduce resistance rates as well as increase the effectiveness of treatment, oral antibiotics should be generally be combined with topical acne creams such as benzoyl peroxide or a retinoid (tretinoin, adapalene, etc). 
Minocycline is also used for other skin infections such as methicillin-resistant Staphylococcus aureus as well as Lyme disease, as the one pill twice daily 100-mg dosage is far easier for patients than the four times a day required with tetracycline or oxytetracycline. Its superior ability to cross the blood-brain barrier adds to its effectiveness against Lyme disease.
Although minocycline's broader spectrum of activity, compared with other members of the group, includes activity against Neisseria meningitidis, its use for prophylaxis is no longer recommended because of side effects (dizziness and vertigo).
A list of uses includes:
- Amoebic dysentery
- Bubonic plague
- Gonorrhea (when penicillin cannot be given)
- Gougerot-Carteaud syndrome (confluent and reticulated papillomatosis)
- Hidradenitis suppurativa
- HIV—for use as an adjuvant to HAART
- Periodontal disease
- Perioral dermatitis
- Respiratory infections such as pneumonia
- Rocky Mountain spotted fever
- Syphilis (when penicillin cannot be given)
- Urinary tract infections, rectal infections, and infections of the cervix caused by certain microbes
- Japanese encephalitis
- Acute encephalitis syndrome
Both minocycline and doxycycline have shown effectiveness in asthma due to immune-suppressing effects. Minocycline and doxycycline have modest effectiveness in treating rheumatoid arthritis. However, the 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis does not include minocycline.
Minocycline may cause upset stomach, diarrhea, dizziness, unsteadiness, drowsiness, mouth sores, headache, and vomiting. It increases sensitivity to sunlight, and may affect the quality of sleep and rarely causes sleep disorders. It has also been linked to cases of lupus. Prolonged use of minocycline can lead to blue-gray staining of skin, fingernails, and scar tissue. This staining is not permanent, but can take a very long time for the skin color to return to normal; however, a muddy brown skin color in sun-exposed areas is usually permanent. Permanent blue discoloration of gums or teeth discoloration may also occur. Rare but serious side effects include fever, yellowing of the eyes or skin, stomach pain, sore throat, vision changes, and mental changes, including depersonalization.
Occasionally, minocycline therapy may result in autoimmune disorders such as drug-related lupus and autoimmune hepatitis, which usually occurs in men who also developed minocycline-induced lupus; however, women are more likely to develop minocycline-induced lupus. Significant or complete recovery occurs in most people who develop minocycline-induced autoimmune problems within a period of a few weeks to a year of cessation of minocycline therapy. Autoimmune problems emerge during chronic therapy, but can sometimes occur after only short courses of a couple of weeks of therapy. Drug reaction with eosinophilia and systemic symptoms syndrome can occur during the first few weeks of therapy with minocycline.
Minocycline, but not other tetracyclines, can cause vestibular disturbances with dizziness, ataxia, vertigo, and tinnitus. These effects are thought to be related to minocycline's greater penetration into the central nervous system. Vestibular side effects are much more common in women than in men, occurring in 50 to 70% of women receiving minocycline. As a result of the frequency of this bothersome side effect, minocycline is rarely used in female patients.
Symptoms of an allergic reaction include rash, itching, swelling, severe dizziness, and trouble breathing. Minocycline has also been reported to very rarely cause idiopathic intracranial hypertension (pseudotumor cerebri), a side effect also more common in female patients, potentially leading to permanent vision damage if not recognized early and treated.
Contrary to most other tetracycline antibiotics (doxycycline excluded), minocycline may be used in those with kidney disease, but may aggravate systemic lupus erythematosus. It may also trigger or unmask autoimmune hepatitis.
Also, more so than other tetracyclines, minocycline can cause the rare condition of secondary intracranial hypertension, which has initial symptoms of headache, visual disturbances, dizziness, vomiting, and confusion. Brain swelling and rheumatoid arthritis are rare side effects of minocycline in some people.
Minocycline, like most tetracyclines, becomes dangerous past its expiration date. While most prescription drugs lose potency after their expiration dates, tetracyclines are known to become toxic over time. Expired tetracyclines can cause serious damage to the kidney due to the formation of a degradation product, anhydro-4-epitetracycline. Minocycline's absorption is impaired if taken at the same time of day as calcium or iron supplements. Unlike some of the other tetracycline group antibiotics, it can be taken with calcium-rich foods such as milk, although this does reduce the absorption slightly.
Minocycline, like other tetracyclines, is associated with esophageal irritation and ulceration if insufficient fluids are taken with the drug before sleep.
A 2007 study suggested that minocycline harms amyotrophic lateral sclerosis patients. Patients on minocycline declined more rapidly than those on placebo. The mechanism of this side effect is unknown, although a hypothesis is that the drug exacerbated an autoimmune component of the primary disease. The effect does not seem to be dose-dependent because the patients on high doses did not do worse than those on the low doses.
- PARP1 inhibition Ki = 13.8 nM 
- Neuroprotection IC50 = 10 nM 
- Microglia full inhibition = 20 nM 
- Suppression of the mouse's locomotor activity = 0.5 mg/kg 
Anti-inflammatory and neuroprotective
NMDA receptor antagonists induce cortical apoptosis in perinatal rodents and sustain schizophrenia-like alterations that are ameliorated by treatment with antipsychotics. Minocycline with antipsychotic and neuroprotective effects exacerbated dizocilpine (MK-801)-induced brain-cell apoptosis without protection.
In various models of neurodegenerative disease, minocycline has demonstrated both neurorestorative and neuroprotective properties. Neurodegenerative diseases such as Huntington's disease and Parkinson's disease have shown a particularly beneficial response to minocycline in research studies, and an antipsychotic benefit has been found in people with schizophrenia, and minocycline is proposed as a possible add-on therapy for some schizophrenics. Current research is examining the possible neuroprotective and anti-inflammatory effects of minocycline against the progression of a group of neurodegenerative disorders including multiple sclerosis, rheumatoid arthritis, Huntington's disease, and Parkinson's disease. As mentioned above, minocycline harms ALS patients.
Minocycline may exhibit neuroprotective action against AIDS dementia complex by inhibiting macrophage inflammation and HIV replication in the brain and cerebrospinal fluid. Minocycline may suppress viral replication by reducing T cell activation. The neuroprotective action of minocycline may include its inhibitory effect on 5-lipoxygenase, an inflammatory enzyme associated with brain aging, and the antibiotic is being studied for use in Alzheimer's disease patients. Minocycline may also exert neuroprotective effects independent of its anti-inflammatory properties. Minocycline also has been used as a "last-ditch" treatment for toxoplasmosis in AIDS patients. Minocycline is somewhat neuroprotective in mouse models of Huntington's disease.
As an anti-inflammatory, minocycline inhibits apoptosis (cell death) via attenuation of TNF-alpha, downregulating proinflammatory cytokine output. This effect is mediated by a direct action of minocycline on the activated T cells and on microglia, which results in the decreased ability of T cells to contact microglia, which impairs cytokine production in T cell-microglia signal transduction. Minocycline also inhibits microglial activation, through blockade of NF-kappa B nuclear translocation.
A 2007 study reported the impact of the antibiotic minocycline on clinical and magnetic resonance imaging (MRI) outcomes and serum immune molecules in 40 MS patients over 24 months of open-label minocycline treatment. Despite a moderately high pretreatment relapse rate in the patient group prior to treatment (1.3/year pre-enrollment; 1.2/year during a three-month baseline period), no relapses occurred between months 6 and 24 on minocycline. Also, despite significant MRI disease-activity pretreatment (19/40 scans had gadolinium-enhancing activity during a three-month run-in), the only patient with gadolinium-enhancing lesions on MRI at 12 and 24 months was on half-dose minocycline. Levels of interleukin-12 (IL-12), which at high levels might antagonize the proinflammatory IL-12 receptor, were elevated over 18 months of treatment, as were levels of soluble vascular cell adhesion molecule-1 (VCAM-1). The activity of matrix metalloproteinase-9 was decreased by treatment. Clinical and MRI outcomes in this study were supported by systemic immunological changes and call for further investigation of minocycline in MS.
Patients taking 200 mg of minocycline for five days within 24 hours of an ischemic stroke showed an improvement in functional state and stroke severity over a period of 3 months compared with patients receiving placebo.
A double-blind, placebo-controlled study of minocycline for depression in 2017, adds to the growing body of literature addressing whether depression can be treated with drugs which reduce inflammation and foster nerve growth. The result was significant, suggesting that, in select patients who have failed to respond fully to more commonly used antidepressant drugs, minocycline may be appropriate as an adjunctive therapy for depression, especially considering its relatively good safety profile.
Minocycline was shown to be highly effective in conferring neuroprotection during murine cerebral malaria.
Society and culture
Minocycline is no longer covered by patent, so is marketed under a variety of trade names:
- Minostad (in Europe, for the treatment of acne)
- Arestin (1-mg doses administered locally into periodontal pockets, after scaling and root planing, for treatment of periodontal disease.)
- Solodyn (extended-release, for the treatment of acne)
- Minopen (in Japan)
- Maracyn 2 (for treatment of bacterial infections in aquarium fish and amphibians)
- Quatrocin (in Syria)
- Minox (in Ireland)
- Minoz (in India and Romania)
- Divaine (in India)
Dentomycin (2% minocylcine gel for use in periodontal pockets) StoneBridge Pharma also markets Minocycline as Cleeravue-M in combination with SteriLid eyelid cleanser in the treatment of rosacea blepharitis.
In October 2015, a bottle of 30 of tablets of one brand cost $1,040.41 wholesale. Expensive medications like this were sold through the specialty pharmacy Philidor by Valeant Pharmaceuticals International Inc in a 2015 controversial legal tangle involving both companies.
Early research has found a tentative benefit from minocycline in schizophrenia, with several trials underway. A 2014 meta-analysis found minocycline may reduce negative and total symptom scores and was well tolerated.
- DrugBank: DB01017 (Minocycline)
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