Inhibition of cortical spreading depression by L‐701,324, a novel antagonist at the glycine site of the <i>N</i>‐methyl‐D‐aspartate receptor complex

Obrenovitch, Tihomir P.; Zilkha, E.

doi:10.1111/j.1476-5381.1996.tb15283.x

Cited by 71 publications

(38 citation statements)

References 42 publications

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“…The GABA A receptor is now accepted as a common target for many general anesthetics (Campagna, et al, 2003, Garrett and Gan, 1998, Hara and Harris, 2002, but enhanced GABAergic transmission is unlikely to modulate CSD susceptibility since barbiturates do not suppress CSD (Brand, et al, 1998, Kitahara, et al, 2001, Van Harreveld and Stamm, 1953. Relevant for CSD suppression, however, are the NMDA subtype of glutamate receptors, inhibition of which potently reduces CSD speed and duration, and blocks CSD (Gorelova, et al, 1987, Hernandez-Caceres, et al, 1987, Marrannes, et al, 1988, Obrenovitch and Zilkha, 1996. Interaction with NMDA receptors has thus far been convincingly demonstrated for isoflurane and N 2 O. Isoflurane causes modest inhibition of NMDA receptors, likely via the noncompetitive glycine site (Carla and Moroni, 1992, Dickinson, et al, 2007, Solt, et al, 2006.…”

Section: Discussionmentioning

confidence: 99%

The impact of anesthetics and hyperoxia on cortical spreading depression

Kudo

Nozari

Moskowitz

et al. 2008

Experimental Neurology

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Cortical spreading depression (CSD), a transient neuronal and glial depolarization that propagates slowly across the cerebral cortex, is the putative electrophysiological event underlying migraine aura. It negatively impacts tissue injury during stroke, cerebral contusion and intracranial hemorrhage. Susceptibility to CSD has been assessed in several experimental animal models in vivo, such as after topical KCl application or cathodal stimulation. Various combinations of anesthetics and ambient conditions have been used by different laboratories making comparisons problematic and differences in data difficult to reconcile. We systematically studied CSD susceptibility comparing commonly used experimental anesthetics (isoflurane, α-chloralose, urethane) with or without N 2 O or normobaric hyperoxia (100% O 2 inhalation). The frequency of evoked CSDs, and their propagation speed, duration, and amplitude were recorded during 2 hour topical KCl (1M) application. We found that N 2 O reduced CSD frequency when combined with isoflurane or urethane, but not α-chloralose; N 2 O also decreased CSD propagation speed and duration. Urethane anesthesia was associated with the highest CSD frequency that was comparable to pentobarbital. Inhalation of 100% O 2 did not alter CSD frequency, propagation speed or duration in combination with any of the anesthetics tested. Our data show anesthetic modulation of CSD susceptibility in an experimental model of human disease, underscoring the importance of proper study design for hypothesis testing as well as for comparing results between studies.

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Section: Discussionmentioning

confidence: 99%

The impact of anesthetics and hyperoxia on cortical spreading depression

Kudo

Nozari

Moskowitz

et al. 2008

Experimental Neurology

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“…MK-801 (2 mg/kg i.v. ), at a fully neuroprotective dose (Massieu et al, 1993), blocked SD triggering almost completely (Table 1) (Willette et al, 1994;Obrenovitch and Zilkha, 1996). Furthermore, compounds known not to inhibit SD generation when administered acutely in normal animals (sodium valproate and propranolol) (Ayata et al, 2006) were inactive.…”

Section: Discussionmentioning

confidence: 99%

“…Since Marrannes et al (1988) confirmed that NMDA-R is an important component in the generation and propagation of SD and associated inward currents, a variety of NMDA-R antagonists have been shown to block cortical SD (Marrannes et al, 1988;Lauritzen and Hansen, 1992;Anderson and Andrew, 2002). The role of NMDA [but not kainate or AMPA (␣-amino-3-hydroxy-5-methyl-4-isoxazole propionate) receptors] in SD is suggested by the abilities of MK-801 (dizocilpine) and SKF-10047 (noncompetitive NMDA-R ion channel blockers) (Willette et al, 1994) and L-701,324 and ZD9379 (antagonists of the glycine site of the NMDA-R complex) (Obrenovitch and Zilkha, 1996;Tatlisumak et al, 1998), and CP-101,606 (traxoprodil) and ifenprodil (NR2B subunit-selective antagonists) (Menniti et al, 2000;Faria and Mody, 2004) to inhibit SD initiation and propagation.…”

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confidence: 99%

Effects of Pan- and Subtype-SelectiveN-Methyl-d-aspartate Receptor Antagonists on Cortical Spreading Depression in the Rat: Therapeutic Potential for Migraine

Peeters

Gunthorpe²,

Strijbos³

et al. 2007

J Pharmacol Exp Ther

101

106

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Spreading depression (SD) has long been associated with the underlying pathophysiology of migraine. Evidence that the Nmethyl-D-aspartate (NMDA) glutamate receptor (NMDA-R) is implicated in the generation and propagation of SD has itself been available for more than 15 years. However, to date, there are no reports of NMDA-R antagonists being developed for migraine therapy. In this study, an uncompetitive, pan-NMDA-R blocker, memantine, approved for clinical use, and two antagonists with selectivity for NMDA-R containing the NR2B subunit, (1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol (CP-101,606) and (Ϯ)-(R*,S*)-␣-(4-hydroxyphenyl)-␤-methyl-4-(phenylmethyl)-1-piperidine propanol (Ro 25-6981), were investigated to assess their protective effects against SD in the rat. Under isoflurane anesthesia, d.c. potential and the related cortical blood flow and partial pressure of O 2 (pO 2 ) were recorded simultaneously at separate cortical sites. Drugs (1, 3, and 10 mg/kg i.p.) were given 1 h or 30 min before KCl application to the brain surface. Core temperature and arterial pCO 2 , pO 2 , and pH measurements confirmed physiological stability. KCl induced 7.7 Ϯ 1.8 (mean Ϯ S.D.) SD events with d.c. amplitude of 14.9 Ϯ 2.8 mV.Memantine and CP-101,606 dose-dependently decreased SD event number (to 2.0 Ϯ 1.8 and 2.3 Ϯ 2.9, respectively) and SD amplitude at doses relevant for therapeutic use. Ro 25-6981 also decreased SD events significantly, but less effectively (to 4.5 Ϯ 1.6), without affecting amplitude. These results indicate that NR2B-containing NMDA receptors are key mediators of SD, and as such, memantine-and NR2B-selective antagonists may be useful new therapeutic agents for the treatment of migraine and other SD-related disorders (e.g., stroke and brain injury). Whether chronic, rather than acute, treatment may improve their efficacy remains to be determined.Spreading depression (SD) is a slowly (2-6 mm/min) propagating wave of transiently increased cerebral blood flow, suppressed cortical activity, and loss of membrane potential accompanied by major metabolic disturbance (for review, see Smith et al., 2006). SD can be induced in the brains of all animal species investigated, including human, using a variety of mechanical and chemical methods. Typically, in the anesthetized rat, the brain is surgically exposed using a small craniotomy, and SD is evoked by topical administration of KCl. SD can be detected via a reduction in d.c. amplitude using electrodes placed on the brain surface distant from the SD induction site. Associated changes in extracellular ion concentrations and cerebral blood flow can also be detected with appropriate probes. Changes in cerebral tissue water, This study was supported by Marie Curie Industry Host Fellowship QLG5-CT-2001-60018 and the Fonds Spécial de Recherche de l'Université Catholique de Louvain, Belgium) (to M.P.).

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“…Ketamine, for instance, binds to the NMDA receptor, and during glutamatergic synaptic transmission, it decreases its open probability-and therewith the total sodium influx into a cell. Indeed, the use of non-competitive NMDA receptor antagonists is considered one of the most promising strategies for suppression of spreading depolarizations (Iijima et al, 1992;Obrenovitch and Zilkha, 1996). The first experimental evidence to this effect was obtained in animal experiments and was attributed specifically to NMDA receptor blockade (Marrannes et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

Spreading Depressions as Secondary Insults after Traumatic Injury to the Human Brain

Hartings¹

2012

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE (DD-MM-YYYY)2. REPORT TYPE Annual DATES COVERED (From -To)1 Sept 11 -31 Aug 12 TITLE AND SUBTITLESpreading depressions as secondary insults after traumatic injury to the human brain 5a. CONTRACT NUMBER W81XWH-08-2-0016 injury to the human brain 5b. GRANT NUMBER W91ZSQ8005N668 5c. PROGRAM ELEMENT NUMBER AUTHOR(S)Jed A. Hartings, Ph.D.5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) AND ADDRESS(ES) PERFORMING ORGANIZATION REPORT NUMBERUniversity of Cincinnati Tana Housh University Hall Suite 530 PO Box 210222 Cincinnati, OH 45221-0222 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command 1077 SPONSOR/MONITOR'S REPORT1077 Patchel St, Fort Detrick, MD 21702-5012 NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for public release; distribution unlimited SUPPLEMENTARY NOTES ABSTRACTThis report describes year 4 progress of a multi-center study of neurosurgical TBI patients to determine the effects of spreading depression (SD), measured by electrocorticography, on neurologic outcome. In this year, we have enrolled 42 patients, bringing the study total to 136. Data collection, scoring, and monitoring has been completed for 90 patients. Using data from the present study combined with the pilot study, we published the finding that SD is independently associated with worse outcomes in 103 patients. These results establish SD as a mechanism of secondary injury. These analyses will be repeated with the full cohort from the present study and an advanced prognostic model will be developed based on more refined metrics of SD burden, secondary insults, and TBI pathoanatomy. Overall progress indicates that SD should be targeted therapeutically in a future interventional trial. We also found evidence that SD can be monitored non-invasively by scalp EEG recordings, thus providing a method to extend results to non-surgical TBI patients. SUBJECT TERMS I. INTRODUCTIONSevere TBI often results in delayed complications and deterioration of a patient's condition after initial stabilizati...

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Inhibition of cortical spreading depression by L‐701,324, a novel antagonist at the glycine site of the N‐methyl‐D‐aspartate receptor complex

Cited by 71 publications

References 42 publications

The impact of anesthetics and hyperoxia on cortical spreading depression

The impact of anesthetics and hyperoxia on cortical spreading depression

Effects of Pan- and Subtype-SelectiveN-Methyl-d-aspartate Receptor Antagonists on Cortical Spreading Depression in the Rat: Therapeutic Potential for Migraine

Spreading Depressions as Secondary Insults after Traumatic Injury to the Human Brain

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