Chemistry:Minocycline

From HandWiki

Minocycline, sold under the brand name Minocin among others, is a tetracycline antibiotic medication used to treat a number of bacterial infections such as some occurring in certain forms of pneumonia.[1][2][3] It is generally (but not always) less preferred than the tetracycline doxycycline.[2][3] Minocycline is also used for the treatment of acne and rheumatoid arthritis.[3][4] It is taken by mouth or applied to the skin.[2][4]

Common side effects include nausea, diarrhea, dizziness, allergic reactions, and kidney problems.[2] Serious side effects may include anaphylaxis, a lupus-like syndrome, and easy sunburning.[2] Use in the later part of pregnancy may harm the baby and safety during breastfeeding is unclear.[5] It works by decreasing a bacterium's ability to make protein thus stopping its growth.[2]

Minocycline was patented in 1961 and came into commercial use in 1971.[6] It is available as a generic medication.[3][7] In 2022, it was the 269th most commonly prescribed medication in the United States, with more than 900,000 prescriptions.[8][9]

Medical uses

Minocycline 100-mg capsules manufactured by Ranbaxy Pharmaceuticals

Acne

Minocycline and doxycycline are frequently used for the treatment of acne vulgaris.[10][11][12] Minocycline is specifically indicated to treat inflammatory lesions of non-nodular moderate to severe acne vulgaris in people nine years of age and older.[10][4] Both minocycline and doxycycline have similar levels of effectiveness and common adverse effects for acne, although doxycycline may have a slightly lower risk of adverse side effects.[10][13] Both oral/systemic and more recently topical formulations of minocycline are available to treat acne.[10][14]

Historically, oral minocycline has been an effective treatment for acne vulgaris.[15] However, acne that is caused by antibiotic-resistant bacteria is a growing problem in many countries.[16] 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 combined with topical acne creams such as benzoyl peroxide or a retinoid (tretinoin, adapalene, etc.).[17] There have also been concerns about systemic minocycline having a variety of rare adverse effects in terms of its use to treat acne.[10][18]

Oral minocycline is used to treat acne for up to 3 to 4 months.[10] Data beyond 3 to 4 months are limited.[10]

Other infections

Minocycline is also used for other skin infections such as methicillin-resistant Staphylococcus aureus.[19]

Although minocycline's broader spectrum of activity, compared with other members of the group, includes activity against Neisseria meningitidis,[20] its use for prophylaxis is no longer recommended because of side effects (dizziness and vertigo).

It may be used to treat certain strains of methicillin-resistant S. aureus infection and a disease caused by drug-resistant Acinetobacter spp.[21]

A list of uses includes:

Minocycline has been reported to be effective in the eradication of UTIs and prostatitis.[26][27][28] A 2013 Cochrane review identified and included two comparative clinical trials of minocycline for chronic bacterial prostatitis.[27] For this condition, minocycline has been found to be equivalent or superior to doxycycline,[29][30] equivalent to trimethoprim/sulfamethoxazole,[31][32] and superior to the first-generation cephalosporin cephalexin.[33][27][34] It was also equivalent to the fluoroquinolone ofloxacin in the treatment of chronic bacterial prostatitis caused by Ureaplasma urealyticum.[27][35] Treatment durations of minocycline for chronic bacterial prostatitis have ranged from 2 to 4 weeks.[27][30][32][34][35]

Available forms

Minocycline is available in the form of 50 and 100 mg oral capsules, among a variety of other formulations.[1][36] The oral form of minocycline is usually taken twice daily, once every 12 hours, although divided doses four times daily can also be employed.[1] Extended-release oral forms are also available.[36] A topical formulation is available as well.[10][14][36]

Contraindications

The drug is contraindicated in people with known hypersensitivity to tetracycline antibiotics, as there is complete cross sensitivity in this group. It is also contraindicated in people with severe liver impairment and after the 16th week of pregnancy.[37]

Side effects

Minocycline may cause upset stomach, diarrhea, dizziness, unsteadiness, drowsiness, mouth sores, migraines, and vomiting. It increases sensitivity to sunlight, and may affect the quality of sleep and rarely causes sleep disorders.[38] It has also been linked to cases of lupus.[39] 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.[40] 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.[41][42]

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.[43][44] Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome can occur during the first few weeks of therapy with minocycline.[44]

Minocycline, but not other tetracyclines, can cause vestibular disturbances, including symptoms of dizziness, ataxia, vertigo, and tinnitus.[45][46] These effects are thought to be related to minocycline's greater penetration into the central nervous system. The vestibular side effects are much more common in women than in men, reportedly occurring in 50 to 70% of women receiving minocycline.[45][additional citation(s) needed] However, other sources state that vestibular side effects occur in only 1 to 10% of patients.[46] In any case, other studies have found that side effects occur more frequently in women than in men (~58% vs. 34%, respectively).[46] Due to its vestibular side effects, minocycline has been said to be rarely used in female patients.[45][additional citation(s) needed] Minocycline's vestibular side effects typically resolve after discontinuation of the drug.[47][48][49][50]

Symptoms of an allergic reaction include rash, itching, swelling, severe dizziness, and trouble breathing.[41] Minocycline has also been reported to very rarely cause idiopathic intracranial hypertension (pseudotumor cerebri),[51] a side effect also more common in female patients, potentially leading to permanent vision damage if not recognized early and treated.[52]

Contrary to most other tetracycline antibiotics (doxycycline excluded), minocycline may be used in those with kidney disease, but may aggravate systemic lupus erythematosus.[53] It may also trigger or unmask autoimmune hepatitis.[54]

Minocycline can cause the rare condition of secondary intracranial hypertension, which has initial symptoms of headache, visual disturbances, dizziness, vomiting, and confusion.[55] Brain swelling and rheumatoid arthritis are rare side effects of minocycline in some people.[56]

Minocycline, like most tetracyclines, becomes dangerous past its expiration date.[57] 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.[57] 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.[58]

Minocycline, like other tetracyclines, is associated with esophageal irritation and ulceration if insufficient fluids are taken with the drug before sleep.[59]

A 2007 study suggested that minocycline harms amyotrophic lateral sclerosis (ALS) 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.[60]

Other possible rare side effects of minocycline include hyperpigmentation and hypersensitivity reactions, among others.[10][18] It has been associated with more rare and serious adverse effects than other tetracyclines.[46] Some of the rare adverse effects of minocycline may result in death.[46][18] This has spurred interest in topical instead of systemic minocycline for treatment of acne.[46][10]

Minocycline is another drug known to cause leukopenia.[source? Known by whom?]

Minocycine has shown thyroid toxicity in animals, including in rodents, mini pigs, dogs, and monkeys.[1]

The use of minocycline to treat acne has been associated with skin and gut dysbiosis (see antibiotic misuse).[61]

Overdose

Symptoms of minocycline overdose may include dizziness, nausea, and vomiting.[1] There is no specific antidote for overdose of minocycline and treatment should be symptom-based and supportive.[1] The drug is not removed by hemodialysis or peritoneal dialysis.[1]

Interactions

The combination of minocycline with dairy, antacids, calcium and magnesium supplements, iron products, laxatives containing magnesium, or bile acid sequestrants may decrease minocycline's effectiveness by forming chelates. Combining it with isotretinoin, acitretin or other retinoids can increase the risk for intracranial hypertension. Minocycline significantly reduces concentrations of the anti-HIV drug atazanavir in the body.[37][62]

Pharmacology

Pharmacodynamics

Antibiotic activity

Minocycline mediates its antibiotic activity by binding to the 30S ribosomal subunit of bacteria and thereby inhibiting protein synthesis.[63][64] It is primarily bacteriostatic.[1] The drug is a broad-spectrum antibiotic and shows activity against a wide range of both Gram-positive and Gram-negative bacteria.[63][64][26]

Other activities

Minocycline shows a number of off-target activities in addition to its antibiotic activity.[65][66][64] These include inhibition of matrix metalloproteinases (MMPs), anti-inflammatory effects, antiapoptotic effects, antioxidant effects, and neuroprotective effects.[65][66][64]

Some other reported activities of minocycline include:

Pharmacokinetics

Absorption

Minocycline is quickly and nearly completely absorbed from the upper part of the small intestine. Taking it together with food, including milk, has no relevant influence on resorption. It reaches highest blood plasma concentrations after 1 to 2 hours.

Distribution

The drug has a plasma protein binding of 70 to 75%. It penetrates into almost all tissues; very high concentrations are found in the gallbladder and liver. It crosses the blood–brain barrier better than doxycycline and other tetracyclines, reaching therapeutically relevant concentrations in the cerebrospinal fluid and also in inflamed meninges.[37][71] Minocycline achieves good concentrations in the urinary bladder, and many other tissues.[26] It shows excellent penetration into the prostate gland.[26][72] However, while permeation of prostate tissue and semen is good, levels are lower in prostatic fluid.[26]

Metabolism

Minocycline is inactivated by metabolism in the liver to about 50%. It is primarily metabolized into 9-hydroxyminocycline.[73] Two N-demethylated metabolites are also formed.[73]

Elimination

The rest is predominantly excreted into the gut (in part via the gallbladder, in part directly from blood vessels) and eliminated via the feces. About 10–15% are eliminated via the kidneys. It is excreted about 5 to 10% unchanged in urine.[72] For comparison, other tetracyclines, like doxycycline and tetracycline, are excreted 30 to 70% unchanged in urine.[72] The biological half-life of minocycline is 11 to 26 hours in healthy people,[2] up to 30 hours in those with kidney failure,[2] and significantly longer in those with liver disease.[37][71]

Chemistry

Minocycline is a tetracycline derivative.[26][66] It is closely structurally related to other tetracyclic antibiotics such as tetracycline, doxycycline, and tigecycline.[66][26]

The drug is used in form of minocycline hydrochloride dihydrate,[71] which is sparingly soluble in water and slightly soluble in ethanol. Minocycline reacts acidic in aqueous solution.[37]

The partition coefficient (P) of minocycline has been reported to be 39.4 (i.e., log P of 1.60).[74] However, other sources have stated the experimental log P of minocycline to be 0.05,[73] 0.5,[75] and 1.1.[76] In any case, minocycline is consistently described as a highly lipophilic compound with excellent tissue penetration and distribution.[77][74][26] It has been said to be unique among the tetracyclines in that it is the most lipophilic of all of the members of this group.[26] Minocycline has 10 to 30 times greater lipophilicity than tetracycline and 5 times greater lipophilicity than doxycycline.[26][77] The improved lipophilicity of minocycline is thought to be advantageous in terms of its clinical antibiotic effectiveness.[26]

History

Minocycline was patented in 1961, was first described in the scientific literature in 1967,[26] and came into commercial use in 1971.[6] A topical foam for treatment of acne was approved in 2019.[4]

Society and culture

Brand names

  • Minomycin
  • Minostad (in Europe, for the treatment of acne)
  • Akamin
  • Minocin
  • Minoderm
  • Cyclimycin
  • Arestin (1-mg doses administered locally into periodontal pockets, after scaling and root planing, for treatment of periodontal disease.)[78]
  • Nomika (in Indonesia)
  • Aknemin
  • Solodyn (extended-release, for the treatment of acne)
  • Dynacin
  • Sebomin
  • Mino-Tabs
  • Acnamino
  • 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)
  • Vinocyclin 100 (100-mg dose approved for treatment of acne in Vietnam)
  • Dentomycin (2% minocylcine gel for use in periodontal pockets)
  • Amzeeq (4% foam, approved for treatment of acne United States)
  • Zilxi (1.5% foam, approved for treatment of rosacea in the United States)
  • Cleeravue-M

Generic availability

It is available as a generic medication.[3]

Research

Neuropsychiatric disorders

Depression

Minocycline has been studied in the treatment of depression.[79][80][81][82] According to a 2023 systematic review of minocycline for treatment-resistant depression based on four clinical trials, "There is no significant difference with minocycline compared to placebo for depression not responding to first-line antidepressant therapy."[79] Likewise, a 2025 systematic review and meta-analysis of four randomized controlled trials found that minocycline was not significantly more effective than placebo in treating depression.[80] Minocycline might have some benefit in treatment-resistant depression with inflammation however.[81] Yet another meta-analysis, also published in 2023, found that minocycline was effective in the treatment of depression, including treatment-resistant depression, with a small to moderate effect size.[82]

Schizophrenia

Early research has found a tentative benefit from minocycline in schizophrenia,[83] with several trials underway as of 2012.[84] A 2014 meta-analysis found minocycline may reduce negative and total symptom scores and was well tolerated.[85] A 2019 meta-analysis, which included 13 randomized controlled trials, found that minocycline was effective in the treatment of the positive, negative, and general symptoms of schizophrenia, with small to moderate effect sizes.[86] Similarly, a 2023 systematic review and meta-analysis of 10 randomized controlled trials found that minocycline was effective in treating the total, negative, and general symptoms of schizophrenia but not the positive or cognitive symptoms, again with small to moderate effect sizes.[87]

Other conditions

Some early studies suggest that minocycline may be beneficial as an add-on treatment for moderate-to-severe obsessive-compulsive disorder (OCD) when used with a selective serotonin reuptake inhibitor (SSRI).[88][87]

Stroke and neurodegenerative diseases

In ongoing research and trial, minocycline demonstrated efficacy and seems a promising neuroprotective agent in acute stroke patients, especially in AIS subgroup. Further RCTs are needed to evaluate the efficacy and safety of minocycline among ICH patients.[89]

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.[90][91][92][93] As mentioned above, minocycline harms ALS patients. A trial found no difference between minocycline and placebo in people with Alzheimer's disease.[94] Minocycline is somewhat neuroprotective in mouse models of Huntington's disease.[95]

Multiple sclerosis

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.[96][97][98]

Delirium

A 2024 randomized controlled trial found that prophylactic minocycline provided a small but significant decrease in delirium incidence in critically ill patients.[99][100] Unexpectedly, there was also a significant decrease in hospital mortality with minocycline prophylaxis.[99][100] The mortality benefits of minocycline might have simply been due to its bactericidal effects.[101]

Hearing protection

Several preclinical studies (in vitro cell cultures and animal models) suggest that minocycline may have otoprotective benefits. Animal models indicate it could potentially reduce noise-induced and blast-induced hearing loss, possibly by protecting hair cells and mitigating inflammation.[102][103] In vitro and animal studies also show minocycline may help decrease ototoxicity from certain drugs like gentamicin,[104] neomycin,[105] and cisplatin.[106][107]

Other uses

Both minocycline and doxycycline have shown effectiveness in asthma due to immune-suppressing effects.[108] Minocycline and doxycycline have modest effectiveness in treating rheumatoid arthritis.[109] However, the 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis does not include minocycline.[110]

Minocycline also has been used as a "last-ditch" treatment for toxoplasmosis in AIDS patients.[111]

Minocycline has been suggested as a possible treatment for post-COVID-19 syndrome ("long COVID"), but no quality clinical trials exist.[112][113][114] The same is true of minocycline as a potential treatment of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).[113][114][115]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 Cite error: Invalid <ref> tag; no text was provided for refs named Minocin FDA label
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 "Minocycline Hydrochloride Monograph for Professionals". American Society of Health-System Pharmacists. https://www.drugs.com/monograph/minocycline-hydrochloride.html. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 British national formulary: BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 556. ISBN 978-0-85711-338-2. 
  4. ↑ 4.0 4.1 4.2 4.3 "Amzeeq- minocycline aerosol, foam". 25 January 2023. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cc251492-977b-4eb1-a088-a90831324bad. 
  5. ↑ "Minocycline Use During Pregnancy" (in en). https://www.drugs.com/pregnancy/minocycline.html. 
  6. ↑ 6.0 6.1 (in en) Analogue-based Drug Discovery. John Wiley & Sons. 2006. p. 489. ISBN 978-3-527-60749-5. https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA489. 
  7. ↑ "First Generic Drug Approvals". 17 October 2022. https://www.fda.gov/drugs/drug-and-biologic-approval-and-ind-activity-reports/first-generic-drug-approvals. 
  8. ↑ "The Top 300 of 2022". https://clincalc.com/DrugStats/Top300Drugs.aspx. 
  9. ↑ "Minocycline Drug Usage Statistics, United States, 2013 - 2022". https://clincalc.com/DrugStats/Drugs/Minocycline. 
  10. ↑ 10.00 10.01 10.02 10.03 10.04 10.05 10.06 10.07 10.08 10.09 "Guidelines of care for the management of acne vulgaris". J Am Acad Dermatol 90 (5): 1006.e1–1006.e30. May 2024. doi:10.1016/j.jaad.2023.12.017. PMID 38300170. 
  11. ↑ "Guidelines of care for acne vulgaris management". Journal of the American Academy of Dermatology 56 (4): 651–663. April 2007. doi:10.1016/j.jaad.2006.08.048. PMID 17276540. 
  12. ↑ "Minocycline, Doxycycline and Acne Vulgaris". ScienceOfAcne.com. http://scienceofacne.com/doxycycline-and-minocycline/. 
  13. ↑ "Doxycycline and minocycline for the management of acne: a review of efficacy and safety with emphasis on clinical implications". Journal of Drugs in Dermatology 9 (11): 1407–1411. November 2010. PMID 21061764. 
  14. ↑ 14.0 14.1 "Minocycline Topical Foam: A New Drug for the Treatment of Acne". Ann Pharmacother 55 (1): 105–110. January 2021. doi:10.1177/1060028020939926. PMID 32618475. 
  15. ↑ "Efficacy of minocycline compared with tetracycline in treatment of acne vulgaris". Archives of Dermatology 118 (12): 989–992. December 1982. doi:10.1001/archderm.1982.01650240033017. PMID 6216858. 
  16. ↑ "Propionibacterium acnes resistance: a worldwide problem". Dermatology 206 (1): 54–56. 2003. doi:10.1159/000067822. PMID 12566805. 
  17. ↑ "Antibiotic-resistant acne: lessons from Europe". The British Journal of Dermatology 148 (3): 467–478. March 2003. doi:10.1046/j.1365-2133.2003.05067.x. PMID 12653738. 
  18. ↑ 18.0 18.1 18.2 "Adverse Reactions Induced by Minocycline: A Review of Literature". Curr Drug Saf 16 (3): 309–321. 2021. doi:10.2174/1574886316666210120090446. PMID 33494681. 
  19. ↑ "Skin and soft tissue infections". Primary Care 33 (3): 697–710. September 2006. doi:10.1016/j.pop.2006.06.005. PMID 17088156. 
  20. ↑ "Prophylactic use of antibiotics for prevention of meningococcal infections: systematic review and meta-analysis of randomised trials". European Journal of Clinical Microbiology & Infectious Diseases 24 (3): 172–181. March 2005. doi:10.1007/s10096-005-1297-7. PMID 15782277. 
  21. ↑ "Minocycline--an old drug for a new century: emphasis on methicillin-resistant Staphylococcus aureus (MRSA) and Acinetobacter baumannii". International Journal of Antimicrobial Agents 34 (5): 395–401. November 2009. doi:10.1016/j.ijantimicag.2009.06.021. PMID 19665876. 
  22. ↑ "A novel use for an old drug: the potential for minocycline as anti-HIV adjuvant therapy". The Journal of Infectious Diseases 201 (8): 1115–1117. April 2010. doi:10.1086/651278. PMID 20205572. 
  23. ↑ "Mycobacterium leprae: Pathogenesis, diagnosis, and treatment options". Microbial Pathogenesis 149. December 2020. doi:10.1016/j.micpath.2020.104475. PMID 32931893. 
  24. ↑ U.S. National Library of Medicine (11 December 2009) 'Perioral dermatitis'. Retrieved 7 August 2010.
  25. ↑ "Minocycline: Antibiotic Uses, Side Effects & Dosage" (in en). https://www.medicinenet.com/minocycline-oral/article.htm. 
  26. ↑ 26.00 26.01 26.02 26.03 26.04 26.05 26.06 26.07 26.08 26.09 26.10 26.11 "Minocycline". Ther Drug Monit 4 (2): 137–145. 1982. doi:10.1097/00007691-198206000-00002. PMID 7048646. https://journals.lww.com/drug-monitoring/abstract/1982/06000/Minocycline.2.aspx. 
  27. ↑ 27.0 27.1 27.2 27.3 27.4 "Antimicrobial therapy for chronic bacterial prostatitis". Cochrane Database Syst Rev 2013 (8). August 2013. doi:10.1002/14651858.CD009071.pub2. PMID 23934982. 
  28. ↑ "Treatment of chronic bacterial prostatitis". Clin Pharm 3 (1): 49–55. 1984. PMID 6365416. 
  29. ↑ "Minocycline: old and new therapeutic uses". Int J Antimicrob Agents 4 (4): 325–335. 1994. doi:10.1016/0924-8579(94)90034-5. PMID 18611625. "Clinical evaluation was used to compare the effectiveness of minocycline in prostatitis with that of doxycycline [40], cotrimoxazole [41,42], trimethoprim [42], and cephalexin [43]. Standard doses of all antibiotics were employed in these studies, with minocycline being administered orally or IV as a 200 mg loading dose followed by 100 mg twice daily. In all cases, minocycline was found to be as good or better than the comparative agent(s).". 
  30. ↑ 30.0 30.1 "Treatment of chronic prostatitis. Comparison of Minocycline and Doxycycline". Urology 5 (5): 626–631. May 1975. doi:10.1016/0090-4295(75)90114-4. PMID 1093309. 
  31. ↑ "Chronic bacterial prostatitis: theoretical and experimental considerations". Urol Res 11 (1): 1–5. 1983. doi:10.1007/BF00272700. PMID 6344395. "In a recent clinical study, trimethoprim-sulfamethoxazole and minocycline were found equally effective [34], while Ristuccia and Cunha chose doxycycline for the treatment of chronic bacterial prostatis because of its ability to penetrate the prostate, its broad antibacterial spectrum including chlamydia and its few side effects [35].". 
  32. ↑ 32.0 32.1 "Trimethoprium-sulfamethoxazole and minocycline- hydrochloride in the treatment of culture-proved bacterial prostatitis". J Urol 120 (2): 184–185. August 1978. doi:10.1016/s0022-5347(17)57096-2. PMID 671629. 
  33. ↑ "Multidisciplinary approach to prostatitis". Arch Ital Urol Androl 90 (4): 227–248. January 2019. doi:10.4081/aiua.2018.4.227. PMID 30655633. "The antibiotic treatment of chronic prostatitis is currently based on the use of fluoroquinolones that, given for 2 to 4 weeks, cured about 70% of men with chronic bacterial prostatitis. [...] Tetracyclines, especially doxycycline and minocycline, and macrolides have been extensively used to treat CBP. In a RCT minocycline demonstrated better microbiological (45 vs 21%) and clinical (65 vs 46%) cure rates than cephalexin.". 
  34. ↑ 34.0 34.1 "Treatment of bacterial prostatitis. Comparison of cephalexin and minocycline". Urology 27 (4): 379–387. April 1986. doi:10.1016/0090-4295(86)90321-3. PMID 3515737. 
  35. ↑ 35.0 35.1 "Antimicrobial treatment for chronic prostatitis as a means of defining the role of Ureaplasma urealyticum". Urol Int 51 (3): 129–132. 1993. doi:10.1159/000282530. PMID 8249222. 
  36. ↑ 36.0 36.1 36.2 "Drugs@FDA: FDA-Approved Drugs". https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm. 
  37. ↑ 37.0 37.1 37.2 37.3 37.4 Cite error: Invalid <ref> tag; no text was provided for refs named Arzneistoff-Profile
  38. ↑ "Effects of antibiotics, minocycline and ampicillin, on human sleep". Brain Research 288 (1–2): 253–259. December 1983. doi:10.1016/0006-8993(83)90101-4. PMID 6661620. 
  39. ↑ "MedlinePlus Drug Information: Minocycline Oral". https://www.medlineplus.gov/druginfo/meds/a682101.html. 
  40. ↑ "Minocycline-induced skin pigmentation: an update". Acta Dermatovenerologica Croatica 17 (2): 123–126. 2009. PMID 19595269. 
  41. ↑ 41.0 41.1 "minocycline (Dynacin): Antibiotic Side Effects & Dosage". https://www.medicinenet.com/minocycline-oral/article.htm. 
  42. ↑ "Medication-associated depersonalization symptoms: report of transient depersonalization symptoms induced by minocycline". Southern Medical Journal 97 (1): 70–73. January 2004. doi:10.1097/01.SMJ.0000083857.98870.98. PMID 14746427. 
  43. ↑ "Drug insight: autoimmune effects of medications-what's new?". Nature Clinical Practice. Rheumatology 4 (3): 136–144. March 2008. doi:10.1038/ncprheum0708. PMID 18200008. 
  44. ↑ 44.0 44.1 "Minocycline in acne vulgaris: benefits and risks". American Journal of Clinical Dermatology 11 (5): 327–341. 2010. doi:10.2165/11319280-000000000-00000. PMID 20642295. 
  45. ↑ 45.0 45.1 45.2 Infectious Diseases of the Female Genital Tract (4th ed.). Lippincott Williams & Wilkins. 2001. p. 635. "Minocycline, but not the other tetracyclines, can cause vestibular disturbances with dizziness, ataxia, vertigo, and tinnitus. It is reversible when the drug is stopped. This side effect is much more common in women than in men, occurring in 50% to 70% of women receiving minocycline. As a result of this frequent and bothersome side effect, minocycline is rarely used in female patients." 
  46. ↑ 46.0 46.1 46.2 46.3 46.4 46.5 "A Review of Systemic Minocycline Side Effects and Topical Minocycline as a Safer Alternative for Treating Acne and Rosacea". Antibiotics 10 (7): 757. June 2021. doi:10.3390/antibiotics10070757. PMID 34206485. 
  47. ↑ Ototoxic Drugs Exposed (3 ed.). Integrity First Publications. 2010. pp. 435–436. ISBN 978-1-935939-00-9. "You can develop symptoms of ototoxicity after only one or two doses. These symptoms normally disappear a day or two after you stop taking this drug." 
  48. ↑ "Minocycline Side Effects: Common, Severe, Long Term". 27 December 2023. https://www.drugs.com/sfx/minocycline-side-effects.html. "Headache, dizziness, vertigo, and ataxia have been reported. These side effects were reversible within 3 to 48 hours of stopping therapy and occurred less often with low doses." 
  49. ↑ "Minocycline: Possible vestibular side-effects". Lancet 2 (7883): 744–6. September 1974. doi:10.1016/s0140-6736(74)90941-6. PMID 4143012. "17 (89%) of 19 persons taking minocycline for the treatment of bacteriuria or for prophylaxis of meningococcal disease developed nausea, vomiting, weakness, ataxia, vertigo, or dizziness, 24-48 hours after the initiation of therapy. These symptoms usually occurred in combination, were often acute and severe, and disappeared shortly after therapy was discontinued.". 
  50. ↑ "Vestibular reactions associated with minocycline". Antimicrobial Agents and Chemotherapy 8 (4): 453–6. October 1975. doi:10.1128/AAC.8.4.453. PMID 1081373. 
  51. ↑ "Medication-induced intracranial hypertension in dermatology". American Journal of Clinical Dermatology 6 (1): 29–37. 2005. doi:10.2165/00128071-200506010-00004. PMID 15675888. 
  52. ↑ "The Ophthalmic Side Effects of Topiramate: A Review". Cureus 14 (8). August 2022. doi:10.7759/cureus.28513. PMID 36059357. 
  53. ↑ "Minocycline induced autoimmune hepatitis and systemic lupus erythematosus-like syndrome". BMJ 312 (7024): 169–172. January 1996. doi:10.1136/bmj.312.7024.169. PMID 8563540. 
  54. ↑ "Autoimmune hepatitis". The New England Journal of Medicine 354 (1): 54–66. January 2006. doi:10.1056/NEJMra050408. PMID 16394302. 
  55. ↑ "Medication-induced intracranial hypertension in dermatology". American Journal of Clinical Dermatology (Springer Science and Business Media LLC) 6 (1): 29–37. 2005. doi:10.2165/00128071-200506010-00004. PMID 15675888. 
  56. ↑ "Minocycline-induced hypersensitivity syndrome presenting with meningitis and brain edema: a case report". Journal of Medical Case Reports 1. May 2007. doi:10.1186/1752-1947-1-22. PMID 17511865. 
  57. ↑ 57.0 57.1 "Principles and methods for the assessment of nephrotoxicity associated with exposure to chemicals". Environmental health criteria: 119. World Health Organization (WHO). ISBN 92-4-157119-5. ISSN 0250-863X. 1991
  58. ↑ Drug Interactions in Infectious Diseases. Humana Press. 2005. ISBN 978-1-58829-455-5. https://archive.org/details/druginteractions0000unse_u2m5. 
  59. ↑ Drugs.com 'Minocycline Disease Interactions'. Retrieved 12 February 2017.
  60. ↑ "Clinical research. ALS trial raises questions about promising drug". Science 318 (5854): 1227. November 2007. doi:10.1126/science.318.5854.1227a. PMID 18033854. 
  61. ↑ "Minocycline and Its Impact on Microbial Dysbiosis in the Skin and Gastrointestinal Tract of Acne Patients". Annals of Dermatology 32 (1): 21–30. February 2020. doi:10.5021/ad.2020.32.1.21. PMID 33911705. 
  62. ↑ "Minocycline". mediQ. https://www.mediq.ch/. 
  63. ↑ 63.0 63.1 "Minocycline, focus on mechanisms of resistance, antibacterial activity, and clinical effectiveness: Back to the future". J Glob Antimicrob Resist 22: 161–174. September 2020. doi:10.1016/j.jgar.2020.01.022. PMID 32061815. 
  64. ↑ 64.0 64.1 64.2 64.3 "What is behind the non-antibiotic properties of minocycline?". Pharmacol Res 67 (1): 18–30. January 2013. doi:10.1016/j.phrs.2012.10.006. PMID 23085382. 
  65. ↑ 65.0 65.1 "Minocycline and Doxycycline: More Than Antibiotics". Curr Mol Pharmacol 14 (6): 1046–1065. 2021. doi:10.2174/1874467214666210210122628. PMID 33568043. 
  66. ↑ 66.0 66.1 66.2 66.3 "Tetracyclines: drugs with huge therapeutic potential". Mini Rev Med Chem 12 (1): 44–52. January 2012. doi:10.2174/138955712798868977. PMID 22070692. 
  67. ↑ "Minocycline inhibits poly(ADP-ribose) polymerase-1 at nanomolar concentrations". Proceedings of the National Academy of Sciences of the United States of America 103 (25): 9685–9690. June 2006. doi:10.1073/pnas.0600554103. PMID 16769901. Bibcode: 2006PNAS..103.9685A. 
  68. ↑ 68.0 68.1 "Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia". The Journal of Neuroscience 21 (8): 2580–2588. April 2001. doi:10.1523/JNEUROSCI.21-08-02580.2001. PMID 11306611. 
  69. ↑ "minomycin-if". http://www.info.pmda.go.jp/go/interview/2/671450_6152005F1052_2_1F.pdf. 
  70. ↑ "A novel mechanism of action of tetracyclines: effects on nitric oxide synthases". Proceedings of the National Academy of Sciences of the United States of America 93 (24): 14014–14019. November 1996. doi:10.1073/pnas.93.24.14014. PMID 8943052. Bibcode: 1996PNAS...9314014A. 
  71. ↑ 71.0 71.1 71.2 (in de) Austria-Codex. Vienna: Österreichischer Apothekerverlag. 2020. Minostad 50 mg-Kapseln. 
  72. ↑ 72.0 72.1 72.2 "Tetracyclines in urology: current concepts". Urology 36 (6): 548–556. December 1990. doi:10.1016/0090-4295(90)80201-w. PMID 2247929. 
  73. ↑ 73.0 73.1 73.2 "Minocycline: Uses, Interactions, Mechanism of Action". 30 June 1971. https://go.drugbank.com/drugs/DB01017. 
  74. ↑ 74.0 74.1 "Clinical pharmacokinetics of doxycycline and minocycline". Clin Pharmacokinet 15 (6): 355–366. December 1988. doi:10.2165/00003088-198815060-00001. PMID 3072140. 
  75. ↑ "Classification Framework and Chemical Biology of Tetracycline-Structure-Based Drugs". Antibiotics 1 (1): 1–13. June 2012. doi:10.3390/antibiotics1010001. PMID 27029415. 
  76. ↑ "Solubility and Partitioning of Drugs". Physicochemical Principles of Pharmacy. London: Macmillan Education UK. 1988. pp. 131–171. doi:10.1007/978-1-349-16558-2_5. ISBN 978-0-333-23405-1. 
  77. ↑ 77.0 77.1 "Oral antibiotic therapy for acne vulgaris: pharmacokinetic and pharmacodynamic perspectives". J Clin Aesthet Dermatol 4 (2): 40–47. February 2011. PMID 21386956. 
  78. ↑ "How ARESTIN is supplied and dosed". OraPharma, Inc.. http://www.arestin.com/for-professionals-easy-administer.jsp. 
  79. ↑ 79.0 79.1 "Minocycline in depression not responding to first-line therapy: A systematic review and meta-analysis". Medicine (Baltimore) 102 (45). November 2023. doi:10.1097/MD.0000000000035937. PMID 37960804. 
  80. ↑ 80.0 80.1 "Efficacy of Minocycline in Depression: A Systematic Review and Meta-analysis". Clin Neuropharmacol 48 (1): 1–6. 2025. doi:10.1097/WNF.0000000000000618. PMID 39591510. 
  81. ↑ 81.0 81.1 "Role of Minocycline as an Adjunct Neuroinflammatory Modulator in Treatment-Resistant Depression: A Systematic Review of Randomized Controlled Trials". Prim Care Companion CNS Disord 25 (5). September 2023. doi:10.4088/PCC.22r03467. PMID 37713730. "Results: Minocycline as an adjunct immunomodulator shows inconsistent benefit in TRD. Minocycline has some beneficial effect on depression scale scores and inflammatory markers in TRD patients with inflammatory disequilibrium (C-reactive protein elevation exceeds 3 mg/L). However, minocycline showed an inconclusive effect in TRD with no clear immunologic dysregulation.". 
  82. ↑ 82.0 82.1 "Efficacy and tolerability of minocycline in depressive patients with or without treatment-resistant: a meta-analysis of randomized controlled trials". Front Psychiatry 14. 2023. doi:10.3389/fpsyt.2023.1139273. PMID 37342175. 
  83. ↑ "Minocycline: therapeutic potential in psychiatry". CNS Drugs 26 (5): 391–401. May 2012. doi:10.2165/11632000-000000000-00000. PMID 22486246. 
  84. ↑ "Will Antibiotic Fulfill Its Psychosis-Fighting Promise?". Psychiatric News 47 (16): 10. 17 August 2012. doi:10.1176/pn.47.16.psychnews_47_16_10-a. 
  85. ↑ "Efficacy and tolerability of minocycline augmentation therapy in schizophrenia: a systematic review and meta-analysis of randomized controlled trials". Human Psychopharmacology 29 (5): 483–491. September 2014. doi:10.1002/hup.2426. PMID 25087702. 
  86. ↑ "Adjunctive minocycline for major mental disorders: A systematic review". J Psychopharmacol 33 (10): 1215–1226. October 2019. doi:10.1177/0269881119858286. PMID 31294649. 
  87. ↑ 87.0 87.1 "Minocycline as Treatment for Psychiatric and Neurological Conditions: A Systematic Review and Meta-Analysis". International Journal of Molecular Sciences 24 (6): 5250. March 2023. doi:10.3390/ijms24065250. PMID 36982324. 
  88. ↑ "Treatment-resistant OCD: Pharmacotherapies in adults". Comprehensive Psychiatry 120. January 2023. doi:10.1016/j.comppsych.2022.152352. PMID 36368186. 
  89. ↑ "Minocycline for acute stroke treatment: a systematic review and meta-analysis of randomized clinical trials". Journal of Neurology 265 (8): 1871–1879. August 2018. doi:10.1007/s00415-018-8935-3. PMID 29948247. 
  90. ↑ "Preliminary Study Shows Creatine and Minocycline May Warrant Further Study In Parkinson's Disease" (Press release). National Institute of Health. 23 February 2006. Archived from the original on 24 March 2007. Retrieved 22 March 2007.
  91. ↑ "Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease". Nature Medicine 6 (7): 797–801. July 2000. doi:10.1038/77528. PMID 10888929. 
  92. ↑ "Minocycline provides neuroprotection against N-methyl-D-aspartate neurotoxicity by inhibiting microglia". Journal of Immunology 166 (12): 7527–7533. June 2001. doi:10.4049/jimmunol.166.12.7527. PMID 11390507. 
  93. ↑ "Amyotrophic lateral sclerosis: recent advances and future therapies". Current Opinion in Neurology 18 (6): 712–719. December 2005. doi:10.1097/01.wco.0000187248.21103.c5. PMID 16280684. 
  94. ↑ "Minocycline at 2 Different Dosages vs Placebo for Patients With Mild Alzheimer Disease: A Randomized Clinical Trial". JAMA Neurology 77 (2): 164–174. February 2020. doi:10.1001/jamaneurol.2019.3762. PMID 31738372. 
  95. ↑ "Experimental therapeutics in transgenic mouse models of Huntington's disease". Nature Reviews. Neuroscience 5 (5): 373–384. May 2004. doi:10.1038/nrn1386. PMID 15100720. 
  96. ↑ "The potential of minocycline for neuroprotection in human neurologic disease". Clinical Neuropharmacology 27 (6): 293–298. 2004. doi:10.1097/01.wnf.0000150867.98887.3e. PMID 15613934. 
  97. ↑ "Multiple neuroprotective mechanisms of minocycline in autoimmune CNS inflammation". Neurobiology of Disease 25 (3): 514–525. March 2007. doi:10.1016/j.nbd.2006.10.022. PMID 17239606. 
  98. ↑ "Inhibition of autoimmune encephalomyelitis by a tetracycline". Annals of Neurology 51 (2): 215–223. February 2002. doi:10.1002/ana.10092. PMID 11835378. 
  99. ↑ 99.0 99.1 "Epidemiological and clinical characteristics of ammonia-producing microorganisms in the lungs of patients with severe pneumonia: a multicentre cohort study". J Transl Med 22 (1). December 2024. doi:10.1186/s12967-024-05974-2. PMID 39725980. "Dal-Pizzol et al. reported that minocycline could reduce the incidence of delirium and mortality in critically ill patients [26], [...]". 
  100. ↑ 100.0 100.1 "Prophylactic Minocycline for Delirium in Critically Ill Patients: A Randomized Controlled Trial". Chest 165 (5): 1129–1138. May 2024. doi:10.1016/j.chest.2023.11.041. PMID 38043911. 
  101. ↑ "Prophylactic Minocycline for Delirium With Unexpected Death Benefits: What Was Treated Unexpectedly?". Chest 166 (5): e172–e173. November 2024. doi:10.1016/j.chest.2024.05.044. PMID 39521560. 
  102. ↑ "Minocycline attenuates noise-induced hearing loss in rats". Neuroscience Letters 639: 31–35. February 2017. doi:10.1016/j.neulet.2016.12.039. PMID 28007648. 
  103. ↑ "Effect of minocycline and its nano-formulation on central auditory system in blast-induced hearing loss rat model". Journal of Otology 18 (1): 38–48. January 2023. doi:10.1016/j.joto.2022.09.002. PMID 36820161. 
  104. ↑ "Minocycline prevents gentamicin-induced ototoxicity by inhibiting p38 MAP kinase phosphorylation and caspase 3 activation". Neuroscience 131 (2): 513–21. 2005. doi:10.1016/j.neuroscience.2004.11.014. PMID 15708492. 
  105. ↑ "Minocycline protection of neomycin induced hearing loss in gerbils". BioMed Research International 2015. 2015. doi:10.1155/2015/934158. PMID 25950003. 
  106. ↑ "Protective Effect of Minocycline Against Cisplatin-induced Ototoxicity". Clinical and Experimental Otorhinolaryngology 4 (2): 77–82. June 2011. doi:10.3342/ceo.2011.4.2.77. PMID 21716954. 
  107. ↑ "Minocycline attenuates ototoxicity and enhances antitumor activity of cisplatin treatment in vitro". Otolaryngology–Head and Neck Surgery 144 (5): 719–25. May 2011. doi:10.1177/0194599810395090. PMID 21493367. 
  108. ↑ "Non-antibiotic properties of tetracyclines as anti-allergy and asthma drugs". Pharmacological Research 64 (6): 602–609. December 2011. doi:10.1016/j.phrs.2011.04.001. PMID 21501686. 
  109. ↑ "The road forward: the scientific basis for tetracycline treatment of arthritic disorders". Pharmacological Research 64 (6): 610–613. December 2011. doi:10.1016/j.phrs.2011.06.010. PMID 21723947. 
  110. ↑ "Clinical Practice Guidelines: Rheumatoid Arthritis". American College of Rheumatology. https://www.rheumatology.org/Practice-Quality/Clinical-Support/Clinical-Practice-Guidelines/Rheumatoid-Arthritis. 
  111. ↑ "Clarithromycin-minocycline combination as salvage therapy for toxoplasmosis in patients infected with human immunodeficiency virus". Antimicrobial Agents and Chemotherapy 39 (1): 276–277. January 1995. doi:10.1128/AAC.39.1.276. PMID 7695324. 
  112. ↑ "Update of the Potential Treatments for Psychiatric and Neuropsychiatric Symptoms in the Context of the Post-COVID-19 Condition: Still a Lot of Suffering and Many More Things to Learn". Trauma Care 2 (2): 131–150. 24 March 2022. doi:10.3390/traumacare2020011. ISSN 2673-866X. "Other authors also proposed the use of anti-inflammatory medications such as minocycline and tumor necrosis factor (TNF)-alpha inhibitors to treat post-COVID-19 depression, but no clinical study exists for these potential treatments at the time of writing this article [51].". 
  113. ↑ 113.0 113.1 "Could Minocycline Be a "Magic Bullet" for the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome?". Intern Med 60 (16): 2527–2528. August 2021. doi:10.2169/internalmedicine.7182-21. PMID 33814504. 
  114. ↑ 114.0 114.1 "Oral minocycline therapy as first-line treatment in patients with Myalgic encephalomyelitis and long COVID: A pilot study". eNeurologicalSci 38. March 2025. doi:10.1016/j.ensci.2024.100537. PMID 39720104. 
  115. ↑ "Oral Minocycline Therapy Improves Symptoms of Myalgic Encephalomyelitis, Especially in the Initial Disease Stage". Intern Med 60 (16): 2577–2584. August 2021. doi:10.2169/internalmedicine.6082-20. PMID 33896862. 



Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:Minocycline&oldid=4309709"