Title:
INHIBITION OF ERK TO REDUCE OR PREVENT TOLERANCE TO AND DEPENDENCE ON OPIOID ANALGESICS
Document Type and Number:
WIPO Patent Application WO2002058687
Kind Code:
A3
Abstract:
Inhibition of mitogen-activated protein kinases (MAPKs), or more particularly extracellular signal regulated kinases (ERKs) inhibits the development of tolerance to opioid analgesics. Therefore, methods for reducing tolerance, reducing the risk of physical dependence, reducing hyperalgesia, reducing the symptoms of opioid withdrawal or inhibiting pain sensitization are described. MAPK inhibition at the spinal level represents a powerful treatment modality for chronic pain, blocking both neural sensitization induced by pain and factors limiting the effectiveness of opioids, the strongest analgesics currently in use to treat chronic pain.
Inventors:
GUTSTEIN HOWARD B (US)
Application Number:
PCT/US2002/002128
Publication Date:
October 09, 2003
Filing Date:
January 25, 2002
Export Citation:
Assignee:
UNIV TEXAS (US)
GUTSTEIN HOWARD B (US)
GUTSTEIN HOWARD B (US)
International Classes:
A61K31/00; A61K31/122; A61K31/165; A61K31/277; A61K31/4468; A61K31/485; A61K31/7088; A61K38/00; A61K38/45; (IPC1-7): A61K31/277; A61K31/122; A61K31/165; A61K31/7088; A61K38/00
Domestic Patent References:
| WO2002002097A2 | 2002-01-10 |
Other References:
PEARSON P P ET AL.: "ERK Inhibition Reduces Opioid Tolerance in Rats", 2000 ASA MEETING ABSTRACTS, XP002235641, Retrieved from the Internet
DATABASE BIOSIS [online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 2000, PEARSON P P ET AL: "ERK inhibition reduces opioid tolerance in rats.", XP002234656, Database accession no. PREV200100092406
SCHMIDT HARALD ET AL: "Involvement of mitogen-activated protein kinase in agonist-induced phosphorylation of the mu-opioid receptor in HEK 293 cells.", JOURNAL OF NEUROCHEMISTRY, vol. 74, no. 1, January 2000 (2000-01-01), pages 414 - 422, XP002234654, ISSN: 0022-3042
RU-RONG JI ET AL: "NOCICEPTIVE-SPECIFIC ACTIVATION OF ERK IN SPINAL NEURONS CONTRIBUTES TO PAIN HYPERSENSITIVITY", NATURE NEUROSCIENCE, NATURE AMERICA, INC, US, vol. 2, no. 12, December 1999 (1999-12-01), pages 1114 - 1119, XP000978586, ISSN: 1097-6256
LIU JING-GEN ET AL: "Protein kinases modulate the cellular adaptations associated with opioid tolerance and dependence.", BRAIN RESEARCH REVIEWS, vol. 38, no. 1-2, December 2001 (2001-12-01), pages 1 - 19, XP002234655, ISSN: 0165-0173
DATABASE BIOSIS [online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 2000, PEARSON P P ET AL: "ERK inhibition reduces opioid tolerance in rats.", XP002234656, Database accession no. PREV200100092406
SCHMIDT HARALD ET AL: "Involvement of mitogen-activated protein kinase in agonist-induced phosphorylation of the mu-opioid receptor in HEK 293 cells.", JOURNAL OF NEUROCHEMISTRY, vol. 74, no. 1, January 2000 (2000-01-01), pages 414 - 422, XP002234654, ISSN: 0022-3042
RU-RONG JI ET AL: "NOCICEPTIVE-SPECIFIC ACTIVATION OF ERK IN SPINAL NEURONS CONTRIBUTES TO PAIN HYPERSENSITIVITY", NATURE NEUROSCIENCE, NATURE AMERICA, INC, US, vol. 2, no. 12, December 1999 (1999-12-01), pages 1114 - 1119, XP000978586, ISSN: 1097-6256
LIU JING-GEN ET AL: "Protein kinases modulate the cellular adaptations associated with opioid tolerance and dependence.", BRAIN RESEARCH REVIEWS, vol. 38, no. 1-2, December 2001 (2001-12-01), pages 1 - 19, XP002234655, ISSN: 0165-0173
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