A tetracycline called minocycline has pulished research (300+ papers) going back over ten years with very positive results. Yet, no one seems to use it. PLM doesn't list a single soul on it. It seems to have a good safety profile, gets past the BBB, and is a great anti-inflammatory (prevents microglial activation).

So why do we never hear of it? No money to be made?


1. Curr Pharm Des. 2004;10(6):679-86.

Minocycline: neuroprotective mechanisms in Parkinson's disease.

Thomas M, Le WD.

Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA.
weidongl@bcm.tmc.edu

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by
cardinal features of tremor, bradykinesia, rigidity and postural instability. In
addition to the motor symptoms patients experience cognitive decline eventually
resulting in severe disability. Pathologically PD is characterized by
neurodegeneration in the substantia nigra pars compacta (SNc) with
intracytoplasmic inclusions known as Lewy bodies. In addition to the SNc there is
neurodegeneration in other areas including cerebral cortex, raphe nuclei, locus
ceruleus, nucleus basalis of meynert, cranial nerves and autonomic nervous
system. Recent evidence supports the role of inflammation in Parkinson's disease.
Apoptosis has been shown to be one of the pathways of cell death in PD.
Minocycline, a tetracycline derivative is a caspase inhibitor, and also inhibits
the inducible nitric oxide synthase which are important for apoptotic cell death.
Furthermore, Minocycline has been shown to block microglial activation of
6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned
parkinsonism animal models and protect against nigrostriatal dopaminergic
neurodegeneration. In this review, we present the current experimental evidence
for the potential use of tetracycline derivative, minocycline, as a
neuroprotective agent in PD.


PMID: 14965330 [PubMed - indexed for MEDLINE]


1. Behav Brain Res. 2009 Jan 23;196(2):168-79. Epub 2008 Oct 11.

Minocycline and neurodegenerative diseases.

Kim HS, Suh YH.

Department of Pharmacology, Seoul National University, College of Medicine,
Seoul, Republic of Korea.

Minocycline is a semi-synthetic, second-generation tetracycline analog which is
effectively crossing the blood-brain barrier, effective against gram-positive and
-negative infections. In addition to its own antimicrobacterial properties,
minocycline has been reported to exert neuroprotective effects over various
experimental models such as cerebral ischemia, traumatic brain injury,
amyotrophic lateral sclerosis, Parkinson's disease, kainic acid treatment,
Huntington' disease and multiple sclerosis. Minocycline has been focused as a
neuroprotective agent over neurodegenerative disease since it has been first
reported that minocycline has neuroprotective effects in animal models of
ischemic injury [Yrjanheikki J, Keinanen R, Pellikka M, Hokfelt T, Koisinaho J.
Tetracyclines inhibit microglial activation and are neuroprotective in global
brain ischemia. Proc Natl Acad Sci USA 1998;95:15769-74; Yrjanheikki J, Tikka T,
Keinanen R, Goldsteins G, Chan PH, Koistinaho J. A tetracycline derivative,
minocycline, reduces inflammation and protects against focal cerebral ischemia
with a wide therapeutic window. Proc Natl Acad Sci USA 1999;96:13496-500].
Recently, the effect of minocycline on Alzheimer's disease has been also
reported. Although its precise primary target is not clear, the action mechanisms
of minocycline for neuroprotection reported so far are; via; the inhibition of
mitochondrial permeability-transition mediated cytochrome c release from
mitochondria, the inhibition of caspase-1 and -3 expressions, and the suppression
of microglial activation, involvement in some signaling pathways, metalloprotease
activity inhibition. Because of the high tolerance and the excellent penetration
into the brain, minocycline has been clinically tried for some neurodegenerative
diseases such as stroke, multiple sclerosis, spinal cord injury, amyotropic
lateral sclerosis, Hungtington's disease and Parkinson's disease. This review
will briefly summarize the effects and action mechanisms of minocycline on
neurodegenerative diseases.


PMID: 18977395 [PubMed - indexed for MEDLINE]