Voltage-dependent block of excitatory amino acid currents by pentobarbital

Miljkovic, Z.; MacDonald, John F.

doi:10.1016/0006-8993(86)90207-6

Cited by 48 publications

(9 citation statements)

References 18 publications

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“…Stone & Javid, 1980;Turski et al, 1990). A more likely mode of action is a voltagedependent block of channels opened by kainate (Miljkovic & MacDonald, 1986).…”

Section: Discussionmentioning

confidence: 99%

Pharmacological characterization of non‐NMDA subtypes of glutamate receptor in the neonatal rat hemisected spinal cord in vitro

Zeman

Lodge

1992

British J Pharmacology

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1 A grease-gap technique was used to record depolarizing responses to a-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA), kainate and N-methyl-D-aspartate (NMDA) in the hemisected spinal cord of the neonatal rat. The pharmacology of non-NMDA subtypes of glutamate receptor was investigated with the novel quinoxalinedione, 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo (F)-quinoxaline (NBQX) and with a series of barbiturates. 2 NBQX antagonized AMPA-and kainate-, but not NMDA-induced depolarizations. The near parallel shifts of the major part of the dose-response curves for AMPA and kainate by NBQX gave pA2 values (± s.e.) of 6.7 ± 0.2 and 6.8 ± 0.2 respectively, consistent with a common site of action for these two agonists. 3 Below the 50% level at which these pA2 values were calculated, however, an NBQX-resistant plateau was seen within the kainate, but not the AMPA, dose-response curve. 4 In decreasing order of potency, methohexitone, secobarbitone, thiopentone, pentobarbitone and phenobarbitone preferentially reduced kainate-, rather than AMPA-and NMDA-, induced depolarizations. Methohexitone was also the most selective with IC50s against kainate, AMPA and NMDA of 31 ± 7, 172 ± 47 and >200 LLM respectively. 5 The NBQX-resistant plateau seen within the kainate dose-response curve was reduced by methohexitone. Kainate antagonism by methohexitone was not reduced by 50 !LM picrotoxin. 6 We conclude that, while mixed agonist actions may hamper demonstration of antagonist selectivity, depolarizations induced by the non-NMDA ionotropic agonists, AMPA and kainate, are mediated in part via distinct receptors.

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“…Stone & Javid, 1980;Turski et al, 1990). A more likely mode of action is a voltagedependent block of channels opened by kainate (Miljkovic & MacDonald, 1986).…”

Section: Discussionmentioning

confidence: 99%

Pharmacological characterization of non‐NMDA subtypes of glutamate receptor in the neonatal rat hemisected spinal cord in vitro

Zeman

Lodge

1992

British J Pharmacology

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“…To date there have been few studies of the action of general anaesthetics on the sub-types of ionotropic receptor although barbiturates have been shown to depress the sensitivity of hippocampal neurones to ionophoretically-applied NMDA and kainate (Sawada & Yamamoto, 1985). Moreover, pentobarbitone has been found to block currents activated by kainate and L-aspartate more effectively at negative membrane potentials (Miljkovic & MacDonald, 1986). Unlike nictonic receptors which have relatively simple kinetics, NMDA receptors have multiple open and closed states (Gibb & Colquhoun, 1992).…”

Section: Introductionmentioning

confidence: 99%

Pentobarbitone modulation of NMDA receptors in neurones isolated from the rat olfactory brain

Charlesworth¹,

Jacobson²,

Richards³

1995

British J Pharmacology

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“…Moreover, PB is able to activate directly the GABA A receptors in the absence of GABA (Rho et al, 1996). Electrophysiological and biochemical studies have provided evidence that PB, at relatively low concentrations, inhibits responses mediated by excitatory amino-acid (non-NMDA) receptors (Miljkovic and MacDonald, 1986;Frandsen et al, 1990;Ko et al, 1997). Hence, the increment of GABA concentration into synaptic clefts after the inhibition of GABA degradation by VGB associated with the prolongation of time channel opening of postsynaptic GABA A receptors and inhibition of excitatory amino-acid-mediated neurotransmission by PB may contribute to the appearance of synergy between these AEDs with respect to their anticonvulsant activities in the PTZinduced seizure model in mice.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological and Behavioral Characteristics of Interactions between Vigabatrin and Conventional Antiepileptic Drugs in Pentylenetetrazole-Induced Seizures in Mice: An Isobolographic Analysis

Łuszczki

Wojcik-Cwikla

Andres

et al. 2004

Neuropsychopharmacol

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To characterize the anticonvulsant effects and types of interactions exerted by mixtures of vigabatrin (VGB) and conventional antiepileptic drugs (valproate (VPA), ethosuximide (ESM), phenobarbital (PB), and clonazepam (CZP)) in pentylenetetrazole (PTZ)-induced seizures in mice, the isobolographic analysis for three fixed-ratio combinations of 1 : 3, 1 : 1, and 3 : 1 was used. The adverse-effect profile of the combinations tested, at the doses corresponding to their median effective doses (ED 50 ) at the fixed-ratio of 1 : 1 against PTZ-induced seizures, was determined by the chimney (motor performance), step-through passive avoidance (long-term memory), pain threshold (pain sensitivity), and Y-maze (general explorative locomotor activity) tests in mice. Additionally, the observed isobolographic interactions were verified in terms of a pharmacokinetic interaction existence. VGB combined with PB or ESM exerted supra-additive (synergistic) interactions against the clonic phase of PTZ-induced seizures, which was associated with the increment of PB or ESM concentrations in the brains of examined animals. The remaining combinations tested (ie VGB þ VPA and VGB þ CZP) occurred additive in the PTZ test, which was associated with no significant changes in the brain concentrations of VPA and CZP. None of the examined combinations exerted motor impairment in the chimney test in mice. In the standard variant of passive avoidance task (current of 0.6 mA; 2 s of stimulus duration), the combinations of VGB þ CZP and VGB þ VPA significantly affected long-term memory in mice. Moreover, VGB in a dose-dependent manner lengthened the latency to the first pain reaction in the pain threshold test in mice. The modified variant of step-through passive avoidance task (current of 0.6 mA; stimulus duration based on the latency from the pain threshold test) revealed no significant changes in the long-term memory of animals for the combinations of VGB þ VPA and VGB þ CZP; so the observed effects in the standard variant of passive avoidance task were a result of the antinociceptive effects produced by VGB. In the Y-maze test, VGB also, in a dose-dependent manner, increased the general explorative locomotor activity of the animals tested. Similarly, the total number of arm entries in the Y-maze was significantly increased for the combinations of VGB þ CZP and VGB þ ESM, but not for VGB þ PB and VGB þ VPA. The application of VGB in combination with PB, ESM, CZP, and VPA suppressed the clonic phase of PTZ-induced seizures, having no harmful or deleterious effects on behavioral functioning of the animals tested, which might be advantageous in further clinical practice.

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Voltage-dependent block of excitatory amino acid currents by pentobarbital

Cited by 48 publications

References 18 publications

Pharmacological characterization of non‐NMDA subtypes of glutamate receptor in the neonatal rat hemisected spinal cord in vitro

Pharmacological characterization of non‐NMDA subtypes of glutamate receptor in the neonatal rat hemisected spinal cord in vitro

Pentobarbitone modulation of NMDA receptors in neurones isolated from the rat olfactory brain

Pharmacological and Behavioral Characteristics of Interactions between Vigabatrin and Conventional Antiepileptic Drugs in Pentylenetetrazole-Induced Seizures in Mice: An Isobolographic Analysis

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