Chemistry:Minocycline

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Short description: Antibiotic medication
Minocycline
Minocycline.svg
Minocycline (model).png
Clinical data
Trade namesMinocin, Amzeeq, others
AHFS/Drugs.comMonograph
MedlinePlusa682101
License data
Pregnancy
category
Routes of
administration		By mouth, intravenous, topical
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability90–100%[4]
Protein binding70–75%[5]
MetabolismLiver[5]
Elimination half-life14–22[5] (11–26[4]) hours
ExcretionMostly fecal, 10–15% renal[5]
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
FormulaC23H27N3O7
Molar mass457.483 g·mol−1
3D model (JSmol)
Specific rotation[math]\displaystyle{ [\alpha]_D^{25} }[/math] = −166°[5]
Solubility in waterLow
 ☒N☑Y (what is this?)  (verify)

Minocycline, sold under the brand name Minocin among others, is a tetracycline antibiotic medication used to treat a number of bacterial infections such as pneumonia.[2][4][7] It is generally (but not always) less preferred than the tetracycline doxycycline.[4][7] Minocycline is also used for the treatment of acne and rheumatoid arthritis.[7][3] It is taken by mouth or applied to the skin.[4][3]

Common side effects include nausea, diarrhea, dizziness, allergic reactions, and kidney problems.[4] Serious side effects may include anaphylaxis, a lupus-like syndrome, and easy sunburning.[4] Use in the later part of pregnancy may harm the baby and safety during breastfeeding is unclear.[8] It works by decreasing a bacterium's ability to make protein thus stopping its growth.[4]

Minocycline was patented in 1961 and came into commercial use in 1971.[9] It is available as a generic medication.[7][10] In 2020, it was the 236th most commonly prescribed medication in the United States, with more than 1 million prescriptions.[11][12]

Medical uses

Minocycline 100-mg capsules manufactured by Ranbaxy Pharmaceuticals

Acne

In the United States, minocycline is indicated to treat inflammatory lesions of non-nodular moderate to severe acne vulgaris in people nine years of age and older.[3]

Minocycline and doxycycline are frequently used for the treatment of acne vulgaris.[13][14] Both of these closely related antibiotics have similar levels of efficacy, although doxycycline has a slightly lower risk of adverse side effects.[15] Historically, minocycline has been an effective treatment for acne vulgaris.[16] However, acne that is caused by antibiotic-resistant bacteria is a growing problem in many countries.[17] 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.).[18]

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:

Other

Both minocycline and doxycycline have shown effectiveness in asthma due to immune-suppressing effects.[25] Minocycline and doxycycline have modest effectiveness in treating rheumatoid arthritis.[26] However, the 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis does not include minocycline.[27] Recent research indicate that centrally infused minocycline attenuates brain microglial activation, neuroinflammation and sympathetic activation during pulmonary hypertension.[28]

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.[5]

Side effects

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.[29] It has also been linked to cases of lupus.[30] 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.[31] 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.[32][33]

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.[34][35] Drug reaction with eosinophilia and systemic symptoms syndrome can occur during the first few weeks of therapy with minocycline.[35]

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.[36] Minocycline's vestibular side effects typically resolve after discontinuation of the drug.[37][38][39][40]

Symptoms of an allergic reaction include rash, itching, swelling, severe dizziness, and trouble breathing.[32] Minocycline has also been reported to very rarely cause idiopathic intracranial hypertension (pseudotumor cerebri),[41] a side effect also more common in female patients, potentially leading to permanent vision damage if not recognized early and treated.[42]

Contrary to most other tetracycline antibiotics (doxycycline excluded), minocycline may be used in those with kidney disease, but may aggravate systemic lupus erythematosus.[43] It may also trigger or unmask autoimmune hepatitis.[44]

Minocycline can cause the rare condition of secondary intracranial hypertension, which has initial symptoms of headache, visual disturbances, dizziness, vomiting, and confusion.[45] Brain swelling and rheumatoid arthritis are rare side effects of minocycline in some people.[46]

Minocycline, like most tetracyclines, becomes dangerous past its expiration date.[47] 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.[47] 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.[48]

Minocycline, like other tetracyclines, is associated with esophageal irritation and ulceration if insufficient fluids are taken with the drug before sleep.[49]

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.[50]

The use of minocycline in acne vulgaris has been associated with skin and gut dysbiosis (see antibiotic misuse).[51]

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.[5][52]

Pharmacology

Mechanism of action

Pharmacokinetics

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 one to two hours and has a plasma protein binding of 70–75%. The substance 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.[5][53]

Minocycline is inactivated by metabolization in the liver to about 50%. 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. The biological half-life is 14–22 (11–26[4]) hours in healthy people, up to 30 hours in those with kidney failure,[4] and significantly longer in those with liver disease.[5][53]

Chemistry

The drug is used in form of minocycline hydrochloride dihydrate,[53] which is sparingly soluble in water and slightly soluble in ethanol. Minocycline reacts acidic in aqueous solution.[5]

History

Minocycline was patented in 1961 and came into commercial use in 1971.[9] A topical foam for treatment of acne was approved in 2019.[3]

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.)[54]
  • 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

It is available as a generic medication.[7]

Research

Early research has found a tentative benefit from minocycline in schizophrenia,[55] with several trials underway.[56] A 2014 meta-analysis found minocycline may reduce negative and total symptom scores and was well tolerated.[57]

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.[58][59][60][61] As mentioned above, minocycline harms ALS patients.[citation needed]

Minocycline is also known to indirectly inhibit inducible nitric oxide synthase.[62]

A trial found no difference between minocycline and placebo in people with Alzheimers' disease.[63] Minocycline also has been used as a "last-ditch" treatment for toxoplasmosis in AIDS patients.[64] Minocycline is somewhat neuroprotective in mouse models of Huntington's disease.[65]

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.[66][67][68]

Minocycline has been studied for treatment-resistant depression. According to a systematic review based on four clinical trials, "There is no significant difference with minocycline compared to placebo for depression not responding to first-line antidepressant therapy."[69]

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.[70]

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.[71][72] In vitro and animal studies also show minocycline may help decrease ototoxicity from certain drugs like gentamicin,[73] neomycin,[74] and cisplatin.[75][76]

Data from cellular and animal models

References

  1. ↑ "Minocycline Use During Pregnancy". 4 December 2018. https://www.drugs.com/pregnancy/minocycline.html. 
  2. ↑ 2.0 2.1 "Minocin- minocycline hydrochloride injection". 28 July 2021. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e415c323-8219-464b-9e3e-72c5a796cdaa. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 "Amzeeq- minocycline aerosol, foam". 25 January 2023. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cc251492-977b-4eb1-a088-a90831324bad. 
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 4.9 "Minocycline Hydrochloride Monograph for Professionals". American Society of Health-System Pharmacists. https://www.drugs.com/monograph/minocycline-hydrochloride.html. 
  5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 5.7 5.8 5.9 "Minocyclin" (in de). Arzneistoff-Profile. 7 (24 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. 2010. ISBN 978-3-7741-9846-3. 
  6. ↑ "Minocycline". https://go.drugbank.com/drugs/DB01017. 
  7. ↑ 7.0 7.1 7.2 7.3 7.4 British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. pp. 556. ISBN 9780857113382. 
  8. ↑ "Minocycline Use During Pregnancy" (in en). https://www.drugs.com/pregnancy/minocycline.html. 
  9. ↑ 9.0 9.1 (in en) Analogue-based Drug Discovery. John Wiley & Sons. 2006. p. 489. ISBN 9783527607495. https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA489. 
  10. ↑ "First Generic Drug Approvals". 17 October 2022. https://www.fda.gov/drugs/drug-and-biologic-approval-and-ind-activity-reports/first-generic-drug-approvals. 
  11. ↑ "The Top 300 of 2020". https://clincalc.com/DrugStats/Top300Drugs.aspx. 
  12. ↑ "Minocycline - Drug Usage Statistics". https://clincalc.com/DrugStats/Drugs/Minocycline. 
  13. ↑ "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. 
  14. ↑ "Minocycline, Doxycycline and Acne Vulgaris". ScienceOfAcne.com. http://scienceofacne.com/doxycycline-and-minocycline/. 
  15. ↑ "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. 
  16. ↑ "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. 
  17. ↑ "Propionibacterium acnes resistance: a worldwide problem". Dermatology 206 (1): 54–56. 2003. doi:10.1159/000067822. PMID 12566805. 
  18. ↑ "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. 
  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: 104475. 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. ↑ "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. 
  26. ↑ "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. 
  27. ↑ "Clinical Practice Guidelines: Rheumatoid Arthritis". American College of Rheumatology. https://www.rheumatology.org/Practice-Quality/Clinical-Support/Clinical-Practice-Guidelines/Rheumatoid-Arthritis. 
  28. ↑ "Involvement of Neuroinflammation in the Pathogenesis of Monocrotaline-Induced Pulmonary Hypertension". Hypertension 71 (6): 1156–1163. June 2018. doi:10.1161/HYPERTENSIONAHA.118.10934. PMID 29712738. 
  29. ↑ "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. 
  30. ↑ "MedlinePlus Drug Information: Minocycline Oral". https://www.nlm.nih.gov/medlineplus/druginfo/meds/a682101.html. 
  31. ↑ "Minocycline-induced skin pigmentation: an update". Acta Dermatovenerologica Croatica 17 (2): 123–126. 2009. PMID 19595269. 
  32. ↑ 32.0 32.1 "minocycline (Dynacin): Antibiotic Side Effects & Dosage". https://www.medicinenet.com/minocycline-oral/article.htm. 
  33. ↑ "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. 
  34. ↑ "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. 
  35. ↑ 35.0 35.1 "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. 
  36. ↑ Infectious Diseases of the Female Genital Tract (4th ed.). Lippincott Williams & Wilkins. 2001. p. 635. 
  37. ↑ Bauman, Neil (2010). Ototoxic Drugs Exposed (3 ed.). Integrity First Publications. 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." 
  38. ↑ "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." 
  39. ↑ "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.". 
  40. ↑ "Vestibular reactions associated with minocycline". Antimicrobial Agents and Chemotherapy 8 (4): 453–6. October 1975. doi:10.1128/AAC.8.4.453. PMID 1081373. 
  41. ↑ "Medication-induced intracranial hypertension in dermatology". American Journal of Clinical Dermatology 6 (1): 29–37. 2005. doi:10.2165/00128071-200506010-00004. PMID 15675888. 
  42. ↑ "The Ophthalmic Side Effects of Topiramate: A Review". Cureus 14 (8): e28513. August 2022. doi:10.7759/cureus.28513. PMID 36059357. 
  43. ↑ "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. 
  44. ↑ "Autoimmune hepatitis". The New England Journal of Medicine 354 (1): 54–66. January 2006. doi:10.1056/NEJMra050408. PMID 16394302. 
  45. ↑ "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. 
  46. ↑ "Minocycline-induced hypersensitivity syndrome presenting with meningitis and brain edema: a case report". Journal of Medical Case Reports 1: 22. May 2007. doi:10.1186/1752-1947-1-22. PMID 17511865. 
  47. ↑ 47.0 47.1 "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
  48. ↑ Drug Interactions in Infectious Diseases. Humana Press. 2005. ISBN 978-1-58829-455-5. https://archive.org/details/druginteractions0000unse_u2m5. 
  49. ↑ Drugs.com 'Minocycline Disease Interactions'. Retrieved 12 February 2017.
  50. ↑ "Clinical research. ALS trial raises questions about promising drug". Science 318 (5854): 1227. November 2007. doi:10.1126/science.318.5854.1227a. PMID 18033854. 
  51. ↑ "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. 
  52. ↑ "Minocycline". mediQ. https://www.mediq.ch/. 
  53. ↑ 53.0 53.1 53.2 (in de) Austria-Codex. Vienna: Österreichischer Apothekerverlag. 2020. Minostad 50 mg-Kapseln. 
  54. ↑ "How ARESTIN is supplied and dosed". OraPharma, Inc.. http://www.arestin.com/for-professionals-easy-administer.jsp. 
  55. ↑ "Minocycline: therapeutic potential in psychiatry". CNS Drugs 26 (5): 391–401. May 2012. doi:10.2165/11632000-000000000-00000. PMID 22486246. 
  56. ↑ "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. 
  57. ↑ "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. 
  58. ↑ "Preliminary Study Shows Creatine and Minocycline May Warrant Further Study In Parkinson's Disease" (Press release). National Institute of Health. 23 February 2006.
  59. ↑ "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. 
  60. ↑ "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. 
  61. ↑ "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. 
  62. ↑ "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. 
  63. ↑ "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. 
  64. ↑ "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. 
  65. ↑ "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. 
  66. ↑ "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. 
  67. ↑ "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. 
  68. ↑ "Inhibition of autoimmune encephalomyelitis by a tetracycline". Annals of Neurology 51 (2): 215–223. February 2002. doi:10.1002/ana.10092. PMID 11835378. 
  69. ↑ "Minocycline in depression not responding to first-line therapy: A systematic review and meta-analysis". Medicine 102 (45): e35937. November 2023. doi:10.1097/MD.0000000000035937. PMID 37960804. 
  70. ↑ "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. 
  71. ↑ "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. 
  72. ↑ "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. 
  73. ↑ "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. 
  74. ↑ "Minocycline protection of neomycin induced hearing loss in gerbils". BioMed Research International 2015: 934158. 2015. doi:10.1155/2015/934158. PMID 25950003. 
  75. ↑ "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. 
  76. ↑ "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. 
  77. ↑ "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. 
  78. ↑ 78.0 78.1 "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. 
  79. ↑ "minomycin-if". http://www.info.pmda.go.jp/go/interview/2/671450_6152005F1052_2_1F.pdf. 



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