Neuroprotective agent riluzole potentiates postsynaptic GABAA receptor function

  title={Neuroprotective agent riluzole potentiates postsynaptic GABAA receptor function},
  author={Y. He and Ann M. Benz and Tao Fu and M. Wang and Douglas F. Covey and Charles F. Zorumski and Steven J. Mennerick},
Molecular mechanisms of interaction between the neuroprotective substance riluzole and GABAA-receptors
Three different molecular mechanisms of interaction of the neuroprotective compound riluzole were observed at two different subtypes of GABAA receptor channels, pointing to the impact of the inhibitory as well as the excitatory synaptic activity as a pharmacological target to counteract chronic excitotoxicity.
Modulation of AMPA receptors in spinal motor neurons by the neuroprotective agent riluzole
An interaction of riluzole with glutamatergic neurotransmission in spinal cord motor neurons is revealed and can contribute to explain its beneficial effect in the ALS treatment.
Anti-allodynic and promotive effect on inhibitory synaptic transmission of riluzole in rat spinal dorsal horn
Riluzole blocks persistent Na+ and Ca2+ currents and modulates release of glutamate via presynaptic NMDA receptors on neonatal rat hypoglossal motoneurons in vitro
Controlling NMDA receptor function and, thus, excitatory transmitter release via modulation of PKC suggests a novel potential target to contrast glutamate excitotoxicity in this motor nucleus.
The Interaction of the Neuroprotective Compounds Riluzole and Phenobarbital with AMPA-Type Glutamate Receptors: A Patch-Clamp Study
Riluzole and phenobarbital modulate AMPA-type receptor channels separately, which could be both characterized as a combination of open-channel block and competitive-block mechanism.
Interaction of Riluzole with the Closed Inactivated State of Kv4.3 Channels
The results suggest that riluzole inhibits Kv4.3 by binding to the closed inactivated state of the channels and that the unbinding of rILuzole occurs from the closed state during depolarization.
Riluzole, neuroprotection and amyotrophic lateral sclerosis.
The present review summarises the known chemical and pharmacological properties of riluzole, and the hypothesis that Na+ conductances may be involved in the processes of neuronal and axonal degeneration in ALS will be explored.
Riluzole in the Treatment of Mood and Anxiety Disorders
Riluzole may hold promise for the treatment of several psychiatric conditions, possibly through its ability to modulate pathologically dysregulated glutamate levels, and merits further investigation.


Effects of the GABA uptake inhibitor tiagabine on inhibitory synaptic potentials in rat hippocampal slice cultures.
It is concluded that GABA uptake plays a significant role in determining the time course of evoked IPSPs and also limits the likelihood that GABAB receptors are activated.
Differential Inhibition by Riluzole, Lamotrigine, and Phenytoin of Sodium and Calcium Currents in Cortical Neurons: Implications for Neuroprotective Strategies
The different pharmacological profiles of the tested agents might indicate that glutamate release blockers do not represent a homogenous class of drugs, and could support their selective utilization in different disease status.
Effects of the neuroprotective agent riluzole on the high voltage-activated calcium channels of rat dorsal root ganglion neurons.
Riluzole inhibition of N- and P/Q-type calcium channels may result in reduced calcium influx at presynaptic terminals, which thereby decreases excessive excitatory neurotransmitter release, especially glutamate, a mechanism known to cause neuronal death in ischemic conditions.
Block of the rat brain IIA sodium channel alpha subunit by the neuroprotective drug riluzole.
The results show that the riluzole binding site is on the alpha subunit of the sodium channel, and they suggest that stabilization of the inactivated state may underlie the neuroprotective properties of rilzole.
Bicuculline and Gabazine Are Allosteric Inhibitors of Channel Opening of the GABAA Receptor
Study of the ability of alphaxalone and pentobarbital to directly activate recombinant GABAA receptors containing the α1, β2, and γ2L subunits concludes that the sites for binding steroids and barbiturates do not overlap with the GABA-binding site.
Lactone Modulation of the γ-Aminobutyric Acid A Receptor: Evidence for a Positive Modulatory Site
A modulatory site on the GABA(A) receptor distinct from that interacting with barbiturates, benzodiazepines, and steroids is identified, showing that the gamma-butyrolactones probably interact at two different sites on the ionophore to produce opposite effects on GABA-mediated current.
GABAA receptor channels.
This chapter discusses the gamma-aminobutyric acid (GABA) receptor channels, which are the most abundant inhibitory neurotransmitter in the CNS. Following release from presynaptic vesicles, GABA
Gamma-butyrolactone antagonism of the picrotoxin receptor: comparison of a pure antagonist and a mixed antagonist/inverse agonist.
Compared to alpha EMGBL, alpha IMGBL had no effect on responses to either 0.5 or 30 microM GABA or on IPSCs, but it was able to block the effects of picrotoxin receptor agonists and inverse agonists, so it is suggested that drugs modulating the GABA-linked chloride ionophore may be specific for the kinetic state of the GABA-gated channel.