Minocycline

Structural formula
General
Non-proprietary name	Minocycline
other names	4 β , 7-bis (dimethylamino) -1,4,4a, 5,5a, 6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacene carboxamide ( IUPAC )
Molecular formula	C 23 H 27 N 3 O 7
Brief description	yellow, crystalline powder (mono hydrochloride )
External identifiers / databases
EC number	800-277-5
ECHA InfoCard	100.226.626
PubChem	54675783
ChemSpider	16735907
DrugBank	DB01017
Wikidata	Q415336
Drug information
ATC code	J01 AA08 , A01 AB23
Drug class	Tetracyclines
properties
Molar mass	457.48 g · mol -1
Melting point	> 175 ° C (decomposition) (monohydrochloride)
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Caution
H and P phrases	H: 315-319-335
	P: 261-305 + 351 + 338
Toxicological data	140 mg kg −1 ( LD 50 , mouse , iv )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Minocycline is an antibiotic belonging to the tetracycline class . It has a broad spectrum of activity and shows a bacteriostatic effect on gram-positive, gram-negative and cell wallless germs . Minocycline is used to treat of infections of the respiratory tract and ear, nose and throat region , certain forms of pneumonia , infections of the urinary tract , the reproductive organs and the gastrointestinal tract as well as skin diseases , severe forms of acne , conjunctivitis and Lyme disease used .

Independent of the antibacterial effect of minocycline, protective effects for nerve cells as well as for the kidneys in diabetes mellitus have been demonstrated since 2000 .

Manufacturing

The multi-stage synthesis of the active ingredient is described in the literature. Starting from 6-demethyltetracycline obtained fermentatively and partially synthetically, a benzylic hydroxyl group is first split off hydrogenolytically . A nitro group is then introduced by reaction with potassium nitrate / hydrofluoric acid in the ortho position to the phenolic hydroxyl group. The corresponding aniline derivative is obtained by reducing this nitro group. With nitrating acid , a nitro group is introduced on the aromatic ring in the para position to the phenolic hydroxyl group. The diazotization of the aniline derivative gives the diazonium salt . The nitrogen of the diazonium salt is split off by catalytic reduction and at the same time the second nitro group (in the para position of the phenol) is reduced to the amino group . This amino group is then methylated twice with formaldehyde, so that minocycline results. The drug thus contains two dimethylamino functions (see box).

Anti-inflammatory and neuroprotective properties

Current research is investigating the potential neuroprotective and anti-inflammatory effects of minocycline against the progression of a group of neurodegenerative diseases such as multiple sclerosis , Huntington 's disease , Parkinson's disease and others, as well as rheumatoid arthritis and stroke .

Minocycline is also used in the treatment of acne and Lyme disease in both the early and later stages. Since it has an intracellular effect and can penetrate the blood-brain barrier well, it is particularly suitable for the treatment of neuroborreliosis in late manifestations with involvement of the central nervous system .

However, a study on the use of minocycline in amyotrophic lateral sclerosis was disappointing and showed that the active ingredient can have a destructive, disease-accelerating effect in this disease.

In the animal model of orofacial pain , minocycline has shown a significantly attenuating effect in deep inflammation- related hyperalgesia of the masseter muscle , but not in hyperalgesia of the subcutaneous tissue . It is believed that the neuroprotective effects of minocycline are independent of the anti-inflammatory properties.

Trade names

Monopreparations

Aknefug Mino (D), Aknoral (CH), Aknosan (D), Minakne (D), Skid (D), Skinocyclin (D), Udima (D, A), numerous generic drugs (D, A, CH), Cyclin ( Taiwan)

literature

Wang, J. et al. Minocycline up-regulates Bcl-2 and protects against cell death in mitochondria. In: J Biol Chem , 279, 19948-19954 (2004).
Kelly, KJ et al. Minocycline inhibits apoptosis and inflammation in a rat model of ischemic renal injury. In: Am J Physiol Renal Physiol , 287, F760-F766 (2004).
Chen, M. et al. Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. In: Nat Med , 6, 797-801 (2000).
Hayakawa, K. et al. Delayed treatment with minocycline ameliorates neurologic impairment through activated microglia expressing a high-mobility group box1 inhibiting mechanism. In: Stroke , 39 (3), 951-958 (2008).

Web links

Entry on minocycline at Vetpharm, accessed August 11, 2012.

Individual evidence

↑ ^a ^b ^c Entry on minocycline. In: Römpp Online . Georg Thieme Verlag, accessed on May 29, 2014.
↑ ^a ^b Data sheet Minocycline hydrochloride from Sigma-Aldrich , accessed on April 10, 2011 ( PDF ).
↑ ^a ^b Maier K, Merkler D, Gerber J, Taheri N, Kuhnert AV, Williams SK, Neusch C, Bähr M, Diem R: Multiple neuroprotective mechanisms of minocycline in autoimmune CNS inflammation . In: Neurobiol. Dis. . 25, No. 3, 2007, pp. 514-525. doi : 10.1016 / j.nbd.2006.10.022 . PMID 17239606 .
↑ ^a ^b Zabad RK, Metz LM, Todoruk TR, Zhang Y, Mitchell JR, Yeung M, Patry DG, Bell RB, Yong VW: The clinical response to minocycline in multiple sclerosis is accompanied by beneficial immune changes: a pilot study . In: Mult. Scler. . 13, No. 4, 2007, pp. 517-526. doi : 10.1177 / 1352458506070319 . PMID 17463074 .
↑ ^a ^b Zemke D, Majid A: The potential of minocycline for neuroprotection in human neurologic disease . In: Clinical Neuropharmacology . 27, No. 6, 2004, pp. 293-298. PMID 15613934 .
^ Axel Kleemann , Jürgen Engel, Bernd Kutscher and Dietmar Reichert: Pharmaceutical Substances, 4th edition (two volumes), Georg Thieme Verlag, Stuttgart 2000, ISBN 978-1-58890-031-9 ; online since 2003 with biannual additions and updates.
↑ National Institute of Health Press release: Preliminary Study Shows Creatine and Minocycline May Warrant Further Study In Parkinson's Disease. February 23, 2006 .
↑ Tikka TM, Koistinaho JE: Minocycline Provides Neuroprotection against N-methyl-D-aspartate neurotoxicity by Inhibiting microglia . In: J. Immunol. . 166, No. 12, June 2001, pp. 7527-33. PMID 11390507 .
↑ Xue M, Mikliaeva EI, Casha S, Zygun D, Demchuk A, Yong VW: Improving Outcomes of Neuroprotection by Minocycline. Guides from Cell Culture and Intracerebral Hemorrhage in Mice . In: American Journal of Pathology . January 2010. doi : 10.2353 / ajpath.2010.090361 . PMID 20110416 .
^ T. McEvoy: Minocyclines: Rheumatoid Arthritis. In: Hospital pharmacy. Volume 51, Number 7, July 2016, pp. 535-538, doi : 10.1310 / hpj5107-535 , PMID 27559186 , PMC 4981101 (free full text).
↑ Lampl Y, Boaz M, Gilad R, et al. : Minocycline treatment in acute stroke: an open-label, evaluator-blinded study . In: Neurology . 69, No. 14, 2007, pp. 1404-1410. doi : 10.1212 / 01.wnl.0000277487.04281.db . PMID 17909152 .
↑ Petra Hopf-Seidel: Sick after a tick bite. Recognize Lyme disease and treat it effectively. Knaur, Munich 2008, p. 244.
↑ Gordon PH, Moore DH, Miller RG, Florence JM, Verheijde JL, Doorish C, Hilton JF, Spitalny GM, MacArthur RB, Mitsumoto H, Neville HE, Boylan K, Mozaffar T, Belsh JM, Ravits J, Bedlack RS, Graves MC, McCluskey LF, Barohn RJ, Tandan R: Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomized trial . In: The Lancet Neurology . 2007 Dec; 6 (12), 2007, p. 75. PMID 17980667 .
↑ Shimizu K, Guo W, Wang H, Zou S, LaGraize SC, Iwata K, Wei F, Dubner R, Ren K: Differential involvement of trigeminal transition zone and laminated subnucleus caudalis in orofacial deep and cutaneous hyperalgesia: the effects of interleukin- 10 and glial inhibitors . In: Molecular Pain . 5, 2009, p. 75. doi : 10.1186 / 1744-8069-5-75 . PMID 20025765 . PMC 2806354 (free full text).

[Römpp-1] Entry on minocycline. In: Römpp Online . Georg Thieme Verlag, accessed on May 29, 2014.

[Sigma-2] Data sheet Minocycline hydrochloride from Sigma-Aldrich , accessed on April 10, 2011 ( PDF ).

[Maier-3] Maier K, Merkler D, Gerber J, Taheri N, Kuhnert AV, Williams SK, Neusch C, Bähr M, Diem R: Multiple neuroprotective mechanisms of minocycline in autoimmune CNS inflammation . In: Neurobiol. Dis. . 25, No. 3, 2007, pp. 514-525. doi : 10.1016 / j.nbd.2006.10.022 . PMID 17239606 .

[Zabad-4] Zabad RK, Metz LM, Todoruk TR, Zhang Y, Mitchell JR, Yeung M, Patry DG, Bell RB, Yong VW: The clinical response to minocycline in multiple sclerosis is accompanied by beneficial immune changes: a pilot study . In: Mult. Scler. . 13, No. 4, 2007, pp. 517-526. doi : 10.1177 / 1352458506070319 . PMID 17463074 .

[Zemke-5] Zemke D, Majid A: The potential of minocycline for neuroprotection in human neurologic disease . In: Clinical Neuropharmacology . 27, No. 6, 2004, pp. 293-298. PMID 15613934 .

[A._Kleemann-6] Axel Kleemann , Jürgen Engel, Bernd Kutscher and Dietmar Reichert: Pharmaceutical Substances, 4th edition (two volumes), Georg Thieme Verlag, Stuttgart 2000, ISBN 978-1-58890-031-9 ; online since 2003 with biannual additions and updates.

[7] National Institute of Health Press release: Preliminary Study Shows Creatine and Minocycline May Warrant Further Study In Parkinson's Disease. February 23, 2006 .

[pmid11390507-8] Tikka TM, Koistinaho JE: Minocycline Provides Neuroprotection against N-methyl-D-aspartate neurotoxicity by Inhibiting microglia . In: J. Immunol. . 166, No. 12, June 2001, pp. 7527-33. PMID 11390507 .

[pmid20110416-9] Xue M, Mikliaeva EI, Casha S, Zygun D, Demchuk A, Yong VW: Improving Outcomes of Neuroprotection by Minocycline. Guides from Cell Culture and Intracerebral Hemorrhage in Mice . In: American Journal of Pathology . January 2010. doi : 10.2353 / ajpath.2010.090361 . PMID 20110416 .

[PMID27559186-10] T. McEvoy: Minocyclines: Rheumatoid Arthritis. In: Hospital pharmacy. Volume 51, Number 7, July 2016, pp. 535-538, doi : 10.1310 / hpj5107-535 , PMID 27559186 , PMC 4981101 (free full text).

[pmid17909152-11] Lampl Y, Boaz M, Gilad R, et al. : Minocycline treatment in acute stroke: an open-label, evaluator-blinded study . In: Neurology . 69, No. 14, 2007, pp. 1404-1410. doi : 10.1212 / 01.wnl.0000277487.04281.db . PMID 17909152 .

[12] Petra Hopf-Seidel: Sick after a tick bite. Recognize Lyme disease and treat it effectively. Knaur, Munich 2008, p. 244.

[13] Gordon PH, Moore DH, Miller RG, Florence JM, Verheijde JL, Doorish C, Hilton JF, Spitalny GM, MacArthur RB, Mitsumoto H, Neville HE, Boylan K, Mozaffar T, Belsh JM, Ravits J, Bedlack RS, Graves MC, McCluskey LF, Barohn RJ, Tandan R: Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomized trial . In: The Lancet Neurology . 2007 Dec; 6 (12), 2007, p. 75. PMID 17980667 .

[14] Shimizu K, Guo W, Wang H, Zou S, LaGraize SC, Iwata K, Wei F, Dubner R, Ren K: Differential involvement of trigeminal transition zone and laminated subnucleus caudalis in orofacial deep and cutaneous hyperalgesia: the effects of interleukin- 10 and glial inhibitors . In: Molecular Pain . 5, 2009, p. 75. doi : 10.1186 / 1744-8069-5-75 . PMID 20025765 . PMC 2806354 (free full text).