Minocycline

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Minocycline
File:Minocycline structure.png
File:Minocycline-from-xtal-PDB-2DRD-3D-balls.png
Systematic (IUPAC) name
(2E,4S,4aR,5aS,12aR)- 2-(amino-hydroxy-methylidene)- 4,7-bis(dimethylamino)- 10,11,12a-trihydroxy-4a,5,5a,6- tetrahydro-4H-tetracene- 1,3,12-trione[1]

OR

(4S,4aS,5aR,12aS,Z)-2-[amino(hydroxy)methylene]-4,7-bis(dimethylamino)-10,11,12a-trihydroxy-4a,5,5a,6-tetrahydrotetracene-1,3,12(2H,4H,12aH)-trione
Clinical data
Routes of
administration
oral
Legal status
Legal status
  • AU: S4 (Prescription only)
Pharmacokinetic data
Bioavailability 100%
Metabolism liver
Biological half-life 11-22 hours
Excretion mostly fecal, rest renal
Identifiers
CAS Number 10118-90-8
ATC code J01AA08 (WHO) A01AB23
PubChem CID 24960
DrugBank APRD00547
ChemSpider 16735907
Chemical data
Formula C23H27N3O7
Molar mass 457.477[[Script error: No such module "String".]]
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Minocycline hydrochloride, also known as minocycline, is a broad spectrum tetracycline antibiotic, and has a broader spectrum than the other members of the group. It is a bacteriostatic antibiotic, classified as a long-acting type. As a result of its long half-life it generally has serum levels 2-4 times that of the simple water-soluble tetracyclines (150 mg giving 16 times the activity levels compared to 250 mg of tetracycline at 24–48 hours).

Minocycline is the most lipid-soluble of the tetracycline-class antibiotics, giving it the greatest penetration into the prostate and brain, but also the greatest amount of central nervous system (CNS)-related side effects. For this reason also, minocycline is a relatively poor tetracycline-class antibiotic for urinary pathogens sensitive to this antibiotic class, as its solubility in water, and levels in the urine, are less than all other tetracyclines.

Minocycline was originally discovered by Lederle Laboratories and marketed under the brand name Minocin.[2]

Indications

File:Minocycline-150.jpg
Minocycline 100 mg Capsules.
It is primarily used to treat acne and other skin infections 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.

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

It may be used to treat certain strains of MRSA infection and disease caused by drug resistant Acinetobacter.

Minocycline is recognized as a DMARD (Disease-Modifying Anti-Rheumatic Drug) by the American College of Rheumatology, which recommends its use as a treatment for mild rheumatoid arthritis.

For other uses of minocycline see tetracycline antibiotics and oxytetracycline as the uses are much the same between tetracyclines with only minor exceptions.

Cautions

Contrary to most other tetracycline antibiotics (doxycycline excluded), minocycline may be used in renal impairment, but may aggravate systemic lupus erythematosus.[3] It may also trigger or unmask autoimmune hepatitis.[4]

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. Cerebral edema, as well as autoimmune rheumatoid arthritis are rare side effects to minocycline in some people.[5]

Minocycline, like all tetracyclines, becomes dangerous past its expiration date. While most prescription drugs lose potency after their expiration dates, tetracyclines were known to become toxic over time due to the breakdown of certain chemicals present in the manufactured capsules. This is not a present concern in drugs manufactured in developed countries. Expired tetracyclines, as previously manufactured, can cause serious damage to the kidneys.

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.[6] Should be taken with plenty of water. If taking this drug, one should avoid prolonged or excessive exposure to direct sunlight. A study published in 2007 mentioned that Minocycline harms ALS patients. Patients on minocycline declined more rapidly than those on placebo. At present the mechanism of this side effect is unknown. According to the researcher from Columbia University 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.[7].

Side effects

Minocycline may cause upset stomach, diarrhea, dizziness, unsteadiness, drowsiness, headache and vomiting. Minocycline increases sensitivity to sunlight. It has also been linked to cases of lupus. Minocycline can reduce the effectiveness of oral contraceptives.[8] Prolonged use of Minocycline over an extended period of time can lead to blue-gray skin (permanent blue discoloration of gums) or teeth discoloration. Rare but serious side effects include fever, yellowing of the eyes or skin, stomach pain, sore throat, vision changes, and mental changes, including depersonalization.[9][10]

Minocycline, but not other tetracyclines, can cause vestibular disturbances with dizziness, ataxia, vertigo and tinnitus. 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 the frequency of this bothersome side effect, minocycline is rarely used in female patients.[11]

Symptoms of an allergic reaction include rash, itching, swelling, severe dizziness, and trouble breathing.[9] Minocycline has also been reported to cause idiopathic intracranial hypertension (pseudotumor cerebri).

Uses

Anti-inflammatory and neuroprotective

Current research is examining the possible neuroprotective and anti-inflammatory effects of minocycline against progression of a group of neurodegenerative disorders including multiple sclerosis (MS), rheumatoid arthritis (RA), amyotrophic lateral sclerosis (ALS), Huntington's disease, and Parkinsons disease.[14][15][16][17]

In the Journal of the American Medical Association (JAMA), Chris Zink, Janice Clements, and colleagues from Johns Hopkins University reported that minocycline may exhibit neuroprotective action against AIDS Dementia Complex by inhibiting macrophage inflammation and HIV replication in the brain and cerebrospinal fluid.[18] Minocycline may suppress viral replication by reducing T cell activation.[19] The neuroprotective action of minocycline may include its inhibitory effect on 5-lipoxygenase,[20] an inflammatory enzyme associated with brain aging, and the antibiotic is being studied for use in Alzheimer's disease patients.[21] Minocycline may also exert neuroprotective effects independent of its anti-inflammatory properties.[22] Minocycline also has been used as a "last ditch" treatment for toxoplasmosis in AIDS patients. Minocycline is neuroprotective in mouse models of amyotrophic lateral sclerosis (ALS) and Huntington's disease and has been recently shown to stabilize the course of Huntington's disease in humans over a 2-year period.

As an anti-inflammatory, minocycline inhibits apoptosis (cell death) via attenuation of TNF-alpha, downregulating pro-inflammatory 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 .[23] Minocycline also inhibits microglial activation, through blockade of NF-kappa B nuclear translocation.

A recent study reported the impact of the antibiotic minocycline on clinical and magnetic resonance imaging (MRI) outcomes and serum immune molecules in MS patients over 24 months of open-label minocycline treatment. Despite a moderately high pretreatment relapse rate in patients in the study prior to treatment, no relapses occurred between months 6 and 24. 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.[24][25][22][26]

A recent study (2007) found that patients taking 200 mg of minocycline for 5 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.[27]

Trade names and availability

Minocycline is no longer covered by patent and is therefore marketed under several trade names:

  • Minomycin
  • Akamin
  • Minocin
  • Minoderm
  • Cyclimycin
  • Arestin (1 mg doses administered locally into periodontal pockets, after scaling and root planing, for treatment of periodontal disease.)[28]
  • Akamin
  • 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)

StoneBridge Pharma also markets Minocycline as Cleeravue-M in combination with SteriLid eyelid cleanser in the treatment of rosacea blepharitis.

References

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External links

de:Minocyclin

es:Minociclina fr:Minocycline it:Minociclina ja:ミノサイクリン pl:Minocyklina pt:Minociclina ru:Миноциклин th:มิโนไซคลีน tr:Minosiklin

zh:米诺环素
  1. DrugBank: DB01017 (Minocycline)
  2. [2] Lin, DW The Tetracyclines March 2005
  3. Gough A, Chapman S, Wagstaff K, Emery P, Elias E (1996). "Minocycline induced autoimmune hepatitis and systemic lupus erythematosus-like syndrome". BMJ. 312 (7024): 169–72. PMC 2349841Freely accessible. PMID 8563540. 
  4. Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  5. Lefebvre N, Forestier E, Farhi D; et al. (2007). "Minocycline-induced hypersensitivity syndrome presenting with meningitis and brain edema: a case report". Journal of Medical Case Reports. 1: 22. doi:10.1186/1752-1947-1-22. PMC 1884162Freely accessible. PMID 17511865. 
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  7. Science Vol 318, 1227, 2007
  8. "MedlinePlus Drug Information: Minocycline Oral". 
  9. 9.0 9.1 MedicineNet: Minocycline Oral (Dynacin, Minocin) - side effects, medical uses, and drug interactions
  10. Cohen, P. R. (2004). "Medication-associated depersonalization symptoms: report of transient depersonalization symptoms induced by minocycline". Southern Medical Journal. 97 (1): 70–73. doi:10.1097/01.SMJ.0000083857.98870.98. PMID 14746427. 
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  12. U.S. National Library of Medicine (2009, Dec 11) 'Perioral dermatitis'. Retrieved 7 August 2010.
  13. Copeland KF, Brooks JI. (15 Apr 2010). "A Novel Use for an Old Drug: The Potential for Minocycline as Anti-HIV Adjuvant Therapy". J Infect Dis. Chicago Press. 201 (8): 1115–7. doi:10.1086/651278. PMID 20205572. Retrieved 21 Mar 2010. 
  14. "Preliminary Study Shows Creatine and Minocycline May Warrant Further Study In Parkinson’s Disease" (Press release). National Institute of Health. February 23, 2006. http://www.nih.gov/news/pr/feb2006/ninds-23.htm. 
  15. Chen M, Ona VO, Li M, Ferrante RJ, Fink KB, Zhu S, Bian J, Guo L, Farrell LA, Hersch SM, Hobbs W, Vonsattel JP, Cha JH, Friedlander RM (2000). "Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease". Nat Med. 6 (7): 797–801. doi:10.1038/80538. PMID 10888929. 
  16. Tikka TM, Koistinaho JE (15 June 2001). "Minocycline provides neuroprotection against N-methyl-D-aspartate neurotoxicity by inhibiting microglia". J Immunol. 166 (12): 7527–33. PMID 11390507. 
  17. Nirmalananthan N, Greensmith L (2005). "Amyotrophic lateral sclerosis: recent advances and future therapies". Curr. Opin. Neurol. 18 (6): 712–9. doi:10.1097/01.wco.0000187248.21103.c5. PMID 16280684. 
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  19. Szeto, G.; Brice, A.; Yang, H.; Barber, S.; Siliciano, R.; Clements, J. (2010). "Minocycline attenuates HIV infection and reactivation by suppressing cellular activation in human CD4+ T cells". The Journal of infectious diseases. 201 (8): 1132–1140. doi:10.1086/651277. PMID 20205570.  edit
  20. Song Y, Wei EQ, Zhang WP, Zhang L, Liu JR, Chen Z (2004). "Minocycline protects PC12 cells from ischemic-like injury and inhibits 5-lipoxygenase activation". Neuroreport. 15 (14): 2181–4. doi:10.1097/00001756-200410050-00007. PMID 15371729. 
  21. Uz T, Pesold C, Longone P, Manev H (1 April 1998). "Aging-associated up-regulation of neuronal 5-lipoxygenase expression: putative role in neuronal vulnerability". FASEB J. 12 (6): 439–49. PMID 9535216. 
  22. 22.0 22.1 Maier K, Merkler D, Gerber J, Taheri N, Kuhnert AV, Williams SK, Neusch C, Bähr M, Diem R (2007). "Multiple neuroprotective mechanisms of minocycline in autoimmune CNS inflammation". Neurobiol. Dis. 25 (3): 514–25. doi:10.1016/j.nbd.2006.10.022. PMID 17239606. 
  23. Giuliani F, Hader W, Yong VW (2005). "Minocycline attenuates T cell and microglia activity to impair cytokine production in T cell-microglia interaction". J. Leukoc. Biol. 78 (1): 135–43. doi:10.1189/jlb.0804477. PMID 15817702. 
  24. Zabad RK, Metz LM, Todoruk TR, Zhang Y, Mitchell JR, Yeung M, Patry DG, Bell RB, Yong VW (2007). "The clinical response to minocycline in multiple sclerosis is accompanied by beneficial immune changes: a pilot study". Mult. Scler. 13 (4): 517–26. doi:10.1177/1352458506070319. PMID 17463074. 
  25. Zemke D, Majid A (2004). "The potential of minocycline for neuroprotection in human neurologic disease". Clinical neuropharmacology. 27 (6): 293–8. doi:10.1097/01.wnf.0000150867.98887.3e. PMID 15613934. 
  26. Popovic N, Schubart A, Goetz BD, Zhang SC, Linington C, Duncan ID (2002). "Inhibition of autoimmune encephalomyelitis by a tetracycline". Ann. Neurol. 51 (2): 215–23. doi:10.1002/ana.10092. PMID 11835378. 
  27. Lampl Y, Boaz M, Gilad R; et al. (2007). "Minocycline treatment in acute stroke: an open-label, evaluator-blinded study". Neurology. 69 (14): 1404–10. doi:10.1212/01.wnl.0000277487.04281.db. PMID 17909152. 
  28. "How ARESTIN® is supplied and dosed". OraPharma, Inc. Retrieved 2010-01-01.