Repurposing an old drug to improve the use and safety of tissue plasminogen activator for acute ischemic stroke: Minocycline

David C. Hess, Susan C. Fagan

Research output: Contribution to journalReview article

15 Citations (Scopus)

Abstract

Tissue plasminogen activator (tPA) is the only drug approved by the United States Food and Drug Administration for treatment of acute ischemic stroke. Because the drug must be used soon after symptom onset and is associated with intracerebral hemorrhage, tPA remains underutilized. Research has therefore focused on identifying other drugs that can be used concomitantly with tPA to improve the odds of a favorable recovery and to reduce the risk of intracerebral hemorrhage. Minocycline is a broad-spectrum antibiotic that has been found to be a neuroprotective agent in preclinical ischemic stroke models. Minocycline inhibits matrix metalloproteinase-9, a biomarker for intracerebral hemorrhage associated with tPA use. Minocycline is also an antiinflammatory agent and inhibits poly(ADP-ribose) polymerase-1. Minocycline has been safe and well tolerated in clinical trials. Additional safety and efficacy data are needed, and a phase III trial of minocycline with tPA in patients experiencing acute ischemic stroke is planned.

Original languageEnglish (US)
Pages (from-to)55S-61S
JournalPharmacotherapy
Volume30
Issue number7 PART 2
DOIs
StatePublished - Jul 1 2010

Fingerprint

Drug Repositioning
Minocycline
Tissue Plasminogen Activator
Stroke
Cerebral Hemorrhage
Safety
Pharmaceutical Preparations
Matrix Metalloproteinase 9
Neuroprotective Agents
United States Food and Drug Administration
Anti-Inflammatory Agents
Biomarkers
Clinical Trials
Anti-Bacterial Agents
Research

Keywords

  • Acute ischemic stroke
  • MMP-9
  • Minocycline
  • PARP-1
  • Tissue plasminogen activator

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Repurposing an old drug to improve the use and safety of tissue plasminogen activator for acute ischemic stroke : Minocycline. / Hess, David C.; Fagan, Susan C.

In: Pharmacotherapy, Vol. 30, No. 7 PART 2, 01.07.2010, p. 55S-61S.

Research output: Contribution to journalReview article

@article{a0504993ecf94e4b97b92d28dfe68414,
title = "Repurposing an old drug to improve the use and safety of tissue plasminogen activator for acute ischemic stroke: Minocycline",
abstract = "Tissue plasminogen activator (tPA) is the only drug approved by the United States Food and Drug Administration for treatment of acute ischemic stroke. Because the drug must be used soon after symptom onset and is associated with intracerebral hemorrhage, tPA remains underutilized. Research has therefore focused on identifying other drugs that can be used concomitantly with tPA to improve the odds of a favorable recovery and to reduce the risk of intracerebral hemorrhage. Minocycline is a broad-spectrum antibiotic that has been found to be a neuroprotective agent in preclinical ischemic stroke models. Minocycline inhibits matrix metalloproteinase-9, a biomarker for intracerebral hemorrhage associated with tPA use. Minocycline is also an antiinflammatory agent and inhibits poly(ADP-ribose) polymerase-1. Minocycline has been safe and well tolerated in clinical trials. Additional safety and efficacy data are needed, and a phase III trial of minocycline with tPA in patients experiencing acute ischemic stroke is planned.",
keywords = "Acute ischemic stroke, MMP-9, Minocycline, PARP-1, Tissue plasminogen activator",
author = "Hess, {David C.} and Fagan, {Susan C.}",
year = "2010",
month = "7",
day = "1",
doi = "10.1592/phco.30.pt2.55S",
language = "English (US)",
volume = "30",
pages = "55S--61S",
journal = "Pharmacotherapy",
issn = "0277-0008",
publisher = "Pharmacotherapy Publications Inc.",
number = "7 PART 2",

}

TY - JOUR

T1 - Repurposing an old drug to improve the use and safety of tissue plasminogen activator for acute ischemic stroke

T2 - Minocycline

AU - Hess, David C.

AU - Fagan, Susan C.

PY - 2010/7/1

Y1 - 2010/7/1

N2 - Tissue plasminogen activator (tPA) is the only drug approved by the United States Food and Drug Administration for treatment of acute ischemic stroke. Because the drug must be used soon after symptom onset and is associated with intracerebral hemorrhage, tPA remains underutilized. Research has therefore focused on identifying other drugs that can be used concomitantly with tPA to improve the odds of a favorable recovery and to reduce the risk of intracerebral hemorrhage. Minocycline is a broad-spectrum antibiotic that has been found to be a neuroprotective agent in preclinical ischemic stroke models. Minocycline inhibits matrix metalloproteinase-9, a biomarker for intracerebral hemorrhage associated with tPA use. Minocycline is also an antiinflammatory agent and inhibits poly(ADP-ribose) polymerase-1. Minocycline has been safe and well tolerated in clinical trials. Additional safety and efficacy data are needed, and a phase III trial of minocycline with tPA in patients experiencing acute ischemic stroke is planned.

AB - Tissue plasminogen activator (tPA) is the only drug approved by the United States Food and Drug Administration for treatment of acute ischemic stroke. Because the drug must be used soon after symptom onset and is associated with intracerebral hemorrhage, tPA remains underutilized. Research has therefore focused on identifying other drugs that can be used concomitantly with tPA to improve the odds of a favorable recovery and to reduce the risk of intracerebral hemorrhage. Minocycline is a broad-spectrum antibiotic that has been found to be a neuroprotective agent in preclinical ischemic stroke models. Minocycline inhibits matrix metalloproteinase-9, a biomarker for intracerebral hemorrhage associated with tPA use. Minocycline is also an antiinflammatory agent and inhibits poly(ADP-ribose) polymerase-1. Minocycline has been safe and well tolerated in clinical trials. Additional safety and efficacy data are needed, and a phase III trial of minocycline with tPA in patients experiencing acute ischemic stroke is planned.

KW - Acute ischemic stroke

KW - MMP-9

KW - Minocycline

KW - PARP-1

KW - Tissue plasminogen activator

UR - http://www.scopus.com/inward/record.url?scp=77954699101&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77954699101&partnerID=8YFLogxK

U2 - 10.1592/phco.30.pt2.55S

DO - 10.1592/phco.30.pt2.55S

M3 - Review article

C2 - 20575623

AN - SCOPUS:77954699101

VL - 30

SP - 55S-61S

JO - Pharmacotherapy

JF - Pharmacotherapy

SN - 0277-0008

IS - 7 PART 2

ER -