The heart and Minocycline

[Guest guest]

After a comment that was made about low dose Mino being tough on the

heart that freaked me out, and I ran out to look.

This is what I found: Did you know that they often interlace parts

being used on the heart with Minocycline and Rifampin????

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Background

Minocycline, a semi-synthetic tetracycline antibiotic, is an

effective neuroprotective agent in animal models of cerebral

ischemia when given in high doses intraperitoneally. The aim of this

study was to determine if minocycline was effective at reducing

infarct size in a Temporary Middle Cerebral Artery Occlusion model

(TMCAO) when given at lower intravenous (IV) doses that correspond

to human clinical exposure regimens.

Methods

Rats underwent 90 minutes of TMCAO. Minocycline or saline placebo

was administered IV starting at 4, 5, or 6 hours post TMCAO. Infarct

volume and neurofunctional tests were carried out at 24 hr after

TMCAO using 2,3,5-triphenyltetrazolium chloride (TTC) brain staining

and Neurological Score evaluation. Pharmacokinetic studies and

hemodynamic monitoring were performed on minocycline-treated rats.

Results

Minocycline at doses of 3 mg/kg and 10 mg/kg IV was effective at

reducing infarct size when administered at 4 hours post TMCAO. At

doses of 3 mg/kg, minocycline reduced infarct size by 42% while 10

mg/kg reduced infarct size by 56%. Minocycline at a dose of 10 mg/kg

significantly reduced infarct size at 5 hours by 40% and the 3 mg/kg

dose significantly reduced infarct size by 34%. With a 6 hour time

window there was a non-significant trend in infarct reduction. There

was a significant difference in neurological scores favoring

minocycline in both the 3 mg/kg and 10 mg/kg doses at 4 hours and at

the 10 mg/kg dose at 5 hours. Minocycline did not significantly

affect hemodynamic and physiological variables. A 3 mg/kg IV dose of

minocycline resulted in serum levels similar to that achieved in

humans after a standard 200 mg dose.

Conclusions

The neuroprotective action of minocycline at clinically suitable

dosing regimens and at a therapeutic time window of at least 4–5

hours merits consideration of phase I trials in humans in view of

developing this drug for treatment of stroke.

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From Wayne State University of Pharmecology:

Minocycline as a new cardioprotective agent

We also investigated the cardioprotective effects of minocycline in

primary cultures of both neonatal and adult cardiac myocytes as well

as in the intact heart. Minocycline is a second-generation

tetracycline with proven safety that is used in humans for the

treatment of acne and urethritis as well as of severe chronic

inflammatory diseases. Our report showed that minocycline

significantly reduced the post-ischemic occurrence of necrotic and

apoptotic cell death, with normalization of developed and diastolic

pressure. In regard to its antiapoptotic mechanism of action, we

observed that minocycline reduced the expression level of initiator

caspases, increased the ratio of XIAP to Smac/DIABLO at both the

mRNA and protein level, and prevented the mitochondria-mediated

release of cytochrome c and Smac/DIABLO. These synergistic actions

dramatically reduced the post-ischemic induction of caspase activity

associated with cardiac ischemia/reperfusion injury. Owing to its

safety record and multiple novel mechanisms of action, minocycline

may be a valuable cardioprotective agent to ameliorate the cardiac

dysfunction and cell loss associated with acute and chronic ischemia

reperfusion injury.

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So Mino seems theraputic for the heart, but what about small doses

taken orally is still the question?