A comparison of (+) SK & F 10047 and MK-801 on cortical spreading depression

doi:10.1016/0006-8993(94)91140-1

Brain Research

Volume 648, Issue 2, 20 June 1994, Pages 347-351

https://doi.org/10.1016/0006-8993(94)91140-1 Get rights and content

Abstract

MK-801 and (+)SK & F 10047 produced a dose-related inhibition of the EEG suppression and cortical hyperemia associated with cortical spreading depression (CSD) and reduced the CSD propagation rate; ED₅₀ = 1mg/kg, i.v. and15mg/kg, i.v., respectively. MK-801 had a delayed onset of action (inversely related to dose) and a prolonged duration of action at all doses (> 2h). In contrast, (+)SK & F 10047 had a rapid onset of action (< 30min) and a predictable dose-related duration of action. These results suggests that an efficacious compound acting with moderate affinity as a non-competitive antagonist at the NMDA-receptor channel may possess a preferable time-course and toxicity profile when compared to agents acting similarly, but with high affinity.

References (22)

LauritzenM. et al.
Quisqualate, kainate and NMDA can initiate spreading depression in the turtle cerebellum
Brain Res.
(1988)
LodgeD. et al.
Noncompetitive excitatory amino acid receptor antagonists
Trends Neurosci.
(1990)
LyskoP.G. et al.
Excitatory amino acid neurotoxicity at the N-methyl-d-aspartate receptor in cultured neurons: protection by SKF 10, 047
Neurosci. Lett.
(1990)
MacDonaldJ.F. et al.
Mechanisms of blockade of excitatory amino acid receptor channels
Trends Neurosci.
(1990)
RogawskiM.A.
Therapeutic potential of noncompetitive NMDA and AMPA/kainate antagonists
Trends Pharmacol. Sci.
(1993)
WoodruffG.N. et al.
The interaction between MK-801 and receptors for N-methyl-d-aspartate: functional consequence
Neuropharmacology
(1987)
BarkelyG.L. et al.
Magnetoencephalographic studies of migraine
Headache
(1990)
CurtisD.R. et al.
Analogues of glutamic acid and gamma-amino-n-butyric acids having potent actions on mammalian neurones
Nature
(1961)
HuettnerJ.E. et al.
Block of N-methyl-d-aspartate-activated current by the anticonvulsant MK-801, selective binding to open channels
JonesS.M. et al.
The anticonvulsant (±)-5-aminocarbonyl-10, 11-dihydro-5H0dibenzo[a,b]cyclohepten-5,10-imine (ADCI) selectivity blocks NMDA-activated current in cultured rat hippocampal neurones: kinetics analysis and comparison with dizocilpine
Mol. Neuropharm.
(1992)

LauritzenM. et al.

The effect of glutamate receptor blockade on anoxic depolarization and cortical spreading depression

J. Cereb. Blood Flow Metab.

(1992)

Cited by (25)

Propofol hemisuccinate suppresses cortical spreading depression
2012, Neuroscience Letters
Citation Excerpt :
The drug solutions were administered intraperitoneally 15 min before cortical application of KCl at doses of 0.1, 0.5 and 2.5 mg/kg. Inhibitory effects of dizocilpine on CSD in rats in vivo have been obtained at doses of 1–10 mg/kg [21,30]. The drugs were administered in a volume of 10 ml/kg.
Propofol is a rapidly acting water-insoluble non-barbiturate anesthetic agent that is widely used as an intravenous sedative–hypnotic agent. Anecdotal evidence indicates that propofol may be effective at terminating intractable migraine headache. Cortical spreading depression (CSD) is believed to be the neural correlate of migraine aura and may be a trigger for migraine pain. Agents that block the induction or slow the spread of CSD may be of utility in treating migraine. Here we examined the ability of propofol hemisuccinate (PHS), a water-soluble prodrug of propofol, to affect CSD in mice. For comparison, we examinined dizocilpine, an NMDA receptor antagonist, that is well recognized to inhibit CSD. When administered 15 min prior to activation of CSD by KCl application to the cortex, intraperitoneal PHS at doses of 120 and 200 mg/kg decreased the number of CSD deflections without an effect on CSD amplitude, and at 200 mg/kg caused a 77% reduction in CSD velocity. The minimally-effective dose of PHS (120 mg/kg) did not cause sedation or motor impairment and while some animals receiving 200 mg/kg did demonstrate motor impariment none exhibited loss-of-righting reflex (anesthesia). Dizocilpine produced comparable inhibition of CSD at doses of 0.5 and 2.5 mg/kg. We conclude that acute PHS treatment inhibits CSD. Our results indicate that propofol, or its prodrug PHS, are worthy of further investigation as a treatment for migraine.
Effects of early aging and cerebral hypoperfusion on spreading depression in rats
2011, Neurobiology of Aging
Citation Excerpt :
This reduced cortex susceptibility to CSD in Middle-age rats agrees with the slower CSD propagation that was previously demonstrated in 24-month-old rats as compared with 3-month-old rats (Guedes et al., 1996). Indeed, slower propagation was found associated with CSD inhibition in a number of previous studies in vivo (Willette et al., 1994; Takaoka et al., 1996; Sonn and Mayevsky, 2001). This decreased sensitivity to CSD in Middle-aged rats contrasts with the previous notion that CSD latency may become shorter with aging as a result of a decreasing threshold of CSD elicitation, due to interstitial space shrinkage that would imply a lower dilution capacity for extracellular K+ (Somjen, 2001).
Cortical spreading depression (CSD) is a feature of stroke pathophysiology. As stroke incidence increases with age, we have examined the effects of early aging and chronic cerebral hypoperfusion on CSD in rats.
Three groups were studied: Young, 2-month-old animals; Middle-aged-2VO, subjected to 8 months of bilateral carotid occlusion from 2-month-of-age; and Middle-aged-SHAM, sham-operated. At 2- and 10-month-of-age for the Young and Middle-aged groups, recurrent CSD were induced under halothane anesthesia, by sustained application of 1 M KCl to the cortex for 2 h. Propagating CSD (i.e., cortical EEG, direct current potential) and associated laser Doppler blood flow changes were recorded anteriorly.
Susceptibility to CSD and event duration were both decreased by early aging (frequency: 21 ± 0.5 and 6 ± 0.5 CSD/h; duration: 139 ± 7 and 63 ± 8 s; in Young and Middle-aged-SHAM, respectively). There was also a tendency for CSD-associated hyperemia to be reduced in the Middle-aged-2VO group (8.9 ± 2.1 vs. 32.8 ± 12.6% × min in Young). These data suggest reduced sensitivity of the cortex to CSD elicitation with early aging, and a less responsive cerebrovascular system with chronic hypoperfusion.
N-methyl-d-aspartate receptor antagonists for migraine: A potential therapeutic approach
2009, Medical Hypotheses
Migraine is one of the most common neurological disorders and still remains incurable. New targets for potential pharmacological intervention should be explored and evaluated for effective long-term management of patients with migraine. N-methyl-d-aspartate receptors (NMDARs) are glutamate-gated ion channels widely expressed in the central nervous system. NMDAR activation has been suggested to be implicated in trigeminovascular system and cortical spreading depression, which are involved in the mechanisms of migraine. Thus, it is reasonable to infer that NMDAR antagonists may provide a potentially novel therapeutic approach to the treatment of migraine. So far, no controlled clinical trial has been published that examines the efficacy of NMDAR antagonist for migraine prophylaxis. It is to be hoped that further studies of NMDAR antagonists, especially NR2B-selective and low-affinity antagonists, will enable the potential of these drugs to be fully tested.
Repetitive spreading depression induces nestin protein expression in the cortex of rats and mice. Is this upregulation initiated by N-methyl-D-aspartate receptors?
2002, Neuroscience Letters
In the November issue (2001) of Neuroscience Letters, Holmin et al. (Neurosci. Lett. 314 (2001) 151) reported that the synthesis of the intermediate filament protein nestin was upregulated by potassium-induced depolarization in the rat cortex. In this letter, we provide supplementary evidence that repeated cortical spreading depression elicited by potassium induces a delayed upregulation of nestin. However, we argue against the authors’ conclusion, “Nestin expression was N-methyl-d-aspartate (NMDA)-receptor dependent since dizocilpine (MK-801) treatment abolished the response” because spreading depression itself is very sensitive to NMDA-receptor block, and the drug treatment was initiated prior to potassium application to the cortex in Holmin et al.’s study.
Sigma receptor agonists provide neuroprotection in vitro by preserving bcl-2
2007, Anesthesia and Analgesia
Sigma (σ)-receptor agonists attenuate brain injury after experimental focal cerebral ischemia in several species. We tested the hypothesis that the potent, prototypical σ₁-receptor agonist, 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP), protects neurons by a mechanism involving the antiapoptotic protein bcl-2.
Primary cortical neuronal cultures were exposed to either 2 h of oxygen–glucose deprivation (OGD) or glutamate (100 μM). PPBP treatment was initiated either 15 min prior to the insult or at 15 min postinsult then continued for 24 h. In another set of experiments, cultured neurons were preincubated for 2 h prior to PPBP treatment with σ₁-receptor antagonist, rimcazole, in a dose-dependent manner. Alive and dead cells were detected with calcein-AM and propidium iodide respectively. Bcl-2 and bax expression were determined by quantitative real time reverse transcription polymerase chain reaction and western blotting, and DNA damage was detected by TUNEL staining.
PPBP pretreatment attenuated neuronal injury induced by OGD or glutamate (50 or 100 μM). This protection was reversed with rimcazole (cell death: OGD 48 ± 2%, OGD plus PPBP 31 ± 3%, OGD plus PPBP with rimcazole 46 ± 2%). PPBP treatment increased bcl-2 but not bax mRNA levels. PPBP's ability to preserve bcl-2 protein after OGD by PPBP was fully abolished by rimcazole. Lastly, PPBP reduced the number of TUNEL-positive cells after OGD, suggesting fewer cells with overt DNA damage.
These data demonstrate that PPBP reduces cell death in vitro by a mechanism involving receptor-dependent preservation of protective genes such as bcl-2
Physiological studies of cortical spreading depression
2006, Biological Reviews of the Cambridge Philosophical Society

View all citing articles on Scopus

View full text

Article preview

Brain Research

Abstract

References (22)

Quisqualate, kainate and NMDA can initiate spreading depression in the turtle cerebellum

Brain Res.

Noncompetitive excitatory amino acid receptor antagonists

Trends Neurosci.

Excitatory amino acid neurotoxicity at the N-methyl-d-aspartate receptor in cultured neurons: protection by SKF 10, 047

Neurosci. Lett.

Mechanisms of blockade of excitatory amino acid receptor channels

Trends Neurosci.

Therapeutic potential of noncompetitive NMDA and AMPA/kainate antagonists

Trends Pharmacol. Sci.

The interaction between MK-801 and receptors for N-methyl-d-aspartate: functional consequence

Neuropharmacology

Magnetoencephalographic studies of migraine

Headache

Analogues of glutamic acid and gamma-amino-n-butyric acids having potent actions on mammalian neurones

Nature

Block of N-methyl-d-aspartate-activated current by the anticonvulsant MK-801, selective binding to open channels

The anticonvulsant (±)-5-aminocarbonyl-10, 11-dihydro-5H0dibenzo[a,b]cyclohepten-5,10-imine (ADCI) selectivity blocks NMDA-activated current in cultured rat hippocampal neurones: kinetics analysis and comparison with dizocilpine

Mol. Neuropharm.

The effect of glutamate receptor blockade on anoxic depolarization and cortical spreading depression

J. Cereb. Blood Flow Metab.

Cited by (25)

Propofol hemisuccinate suppresses cortical spreading depression

Effects of early aging and cerebral hypoperfusion on spreading depression in rats

N-methyl-d-aspartate receptor antagonists for migraine: A potential therapeutic approach

Repetitive spreading depression induces nestin protein expression in the cortex of rats and mice. Is this upregulation initiated by N-methyl-D-aspartate receptors?

Sigma receptor agonists provide neuroprotection in vitro by preserving bcl-2

Physiological studies of cortical spreading depression