α2 adrenergic agonists prevent MK-801 neurotoxicity

Nuri B. Färber; John Foster; Nadine L. Duhan; John W. Olney

doi:10.1016/0893-133X(95)00048-I

α₂ adrenergic agonists prevent MK-801 neurotoxicity

Nuri B. Färber
, John Foster
, Nadine L. Duhan
, John W. Olney

Research output: Contribution to journal › Article › peer-review

45 Scopus citations

Abstract

Antagonists of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor are of considerable interest for various neurotherapeutic purposes, including preventing neuronal degeneration in stroke and CNS trauma, suppressing neuropathic pain and preventing the development of tolerance to opiate analgesics. Unfortunately, NMDA antagonists can cause potentially serious side effects, including acute neurodegenerative changes in corticolimbic regions of the adult rat brain and psychotic reactions in adult humans. We have been investigating the mechanisms underlying the neuropathological changes in rat brain and exploring methods of suppressing or preventing such changes. Here we report that a₂ adrenergic agonists can prevent NMDA antagonist neurotoxicity. Therefore, administering a₂adrenergic agonists together with NMDA antagonists may be a valuable strategy for preventing adverse side effects of NMDA antagonists and making these agents safer for various neurotherapeutic purposes.

Original language	English
Pages (from-to)	347-349
Number of pages	3
Journal	Neuropsychopharmacology
Volume	12
Issue number	4
DOIs	https://doi.org/10.1016/0893-133X(95)00048-I
State	Published - Jul 1995

Keywords

A adrenergic receptor
Clonidine
MK-801
NMDA antagonists
Neurotoxicity
Phencyclidine

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10.1016/0893-133X(95)00048-I

Cite this

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title = "α2 adrenergic agonists prevent MK-801 neurotoxicity",

abstract = "Antagonists of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor are of considerable interest for various neurotherapeutic purposes, including preventing neuronal degeneration in stroke and CNS trauma, suppressing neuropathic pain and preventing the development of tolerance to opiate analgesics. Unfortunately, NMDA antagonists can cause potentially serious side effects, including acute neurodegenerative changes in corticolimbic regions of the adult rat brain and psychotic reactions in adult humans. We have been investigating the mechanisms underlying the neuropathological changes in rat brain and exploring methods of suppressing or preventing such changes. Here we report that a2 adrenergic agonists can prevent NMDA antagonist neurotoxicity. Therefore, administering a2adrenergic agonists together with NMDA antagonists may be a valuable strategy for preventing adverse side effects of NMDA antagonists and making these agents safer for various neurotherapeutic purposes.",

keywords = "A adrenergic receptor, Clonidine, MK-801, NMDA antagonists, Neurotoxicity, Phencyclidine",

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T1 - α2 adrenergic agonists prevent MK-801 neurotoxicity

AU - Färber, Nuri B.

AU - Foster, John

AU - Duhan, Nadine L.

AU - Olney, John W.

PY - 1995/7

Y1 - 1995/7

N2 - Antagonists of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor are of considerable interest for various neurotherapeutic purposes, including preventing neuronal degeneration in stroke and CNS trauma, suppressing neuropathic pain and preventing the development of tolerance to opiate analgesics. Unfortunately, NMDA antagonists can cause potentially serious side effects, including acute neurodegenerative changes in corticolimbic regions of the adult rat brain and psychotic reactions in adult humans. We have been investigating the mechanisms underlying the neuropathological changes in rat brain and exploring methods of suppressing or preventing such changes. Here we report that a2 adrenergic agonists can prevent NMDA antagonist neurotoxicity. Therefore, administering a2adrenergic agonists together with NMDA antagonists may be a valuable strategy for preventing adverse side effects of NMDA antagonists and making these agents safer for various neurotherapeutic purposes.

AB - Antagonists of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor are of considerable interest for various neurotherapeutic purposes, including preventing neuronal degeneration in stroke and CNS trauma, suppressing neuropathic pain and preventing the development of tolerance to opiate analgesics. Unfortunately, NMDA antagonists can cause potentially serious side effects, including acute neurodegenerative changes in corticolimbic regions of the adult rat brain and psychotic reactions in adult humans. We have been investigating the mechanisms underlying the neuropathological changes in rat brain and exploring methods of suppressing or preventing such changes. Here we report that a2 adrenergic agonists can prevent NMDA antagonist neurotoxicity. Therefore, administering a2adrenergic agonists together with NMDA antagonists may be a valuable strategy for preventing adverse side effects of NMDA antagonists and making these agents safer for various neurotherapeutic purposes.

KW - A adrenergic receptor

KW - Clonidine

KW - MK-801

KW - NMDA antagonists

KW - Neurotoxicity

KW - Phencyclidine

UR - https://www.scopus.com/pages/publications/0028983601

U2 - 10.1016/0893-133X(95)00048-I

DO - 10.1016/0893-133X(95)00048-I

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AN - SCOPUS:0028983601

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SP - 347

EP - 349

JO - Neuropsychopharmacology

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IS - 4

ER -

α₂ adrenergic agonists prevent MK-801 neurotoxicity

Abstract

Keywords

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