2-Amino-6-trifluoromethoxy benzothiazole, a possible antagonist of excitatory amino acid neurotransmission—I

Mizoule, J.; Meldrum, Brian S.; Mazadier, Martine; Croucher, Martin J.; Ollat, Catherine; Uzan, A.; Legrand, Jean-Christophe; Guérémy, C.; Fur, G. Le

doi:10.1016/0028-3908(85)90011-5

Cited by 172 publications

(70 citation statements)

References 24 publications

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“…Riluzole, an inhibitor of voltage-gated Na + channels, while not initially developed as an AED, has been found to be a relatively potent anticonvulsant in the MES seizure model. 28 Because the MES study with riluzole was done in mice and not rats we were not able to directly compare its MES seizure activity against its protective activity vis-à-vis NRHypo neurotoxicity. Allowing for inter-species differences in pharmacokinetics, its potency against MES seizures in the mouse (ED 50 = 8.5 mg kg −1 ) is similar to its ED 50 against NRHypo neurotoxicity in the rat, suggesting that the same mechanism, namely inhibition of voltage-gated Na + channels, may underlie its activity in both models.…”

Section: Discussionmentioning

confidence: 99%

Antiepileptic drugs and agents that inhibit voltage-gated sodium channels prevent NMDA antagonist neurotoxicity

et al. 2002

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N-methyl-D-aspartate (NMDA) glutamate receptor antagonists are used in clinical anesthesia and are being developed as therapeutic agents for preventing neurodegeneration in stroke, epilepsy, and brain trauma. However, the ability of these agents to produce neurotoxicity in adult rats and psychosis in adult humans compromises their clinical usefulness. In addition, an NMDA receptor hypofunction (NRHypo) state might play a role in neurodegenerative and psychotic disorders, like Alzheimer's disease, bipolar disorder and schizophrenia. Thus, developing pharmacological means of preventing these NRHypo-induced effects could have significant clinically relevant benefits. NRHypo neurotoxicity appears to be mediated by a complex disinhibition mechanism that results in the excessive stimulation of certain vulnerable neurons. Here we report our findings that five agents (phenytoin, carbamazepine, valproic acid, lamotrigine, and riluzole), thought to possess anticonvulsant activity because they inhibit voltage-gated sodium channels, prevent NRHypo neurotoxicity. The ability of tetrodotoxin, a highly selective inhibitor of voltage-gated sodium channels, to prevent the same neurotoxicity suggests that inhibition of this ion channel is the likely mechanism of action of these five agents. We also found that three other anticonvulsants (felbamate, gabapentin and ethosuximide), whose mechanism is less clear, also prevent NRHypo neurotoxicity, suggesting that inhibition of voltage-gated sodium channels is not the only mechanism via which anticonvulsants can act to prevent NRHypo neurotoxicity. Several of these agents have been found to be of clinical use in bipolar disorder. It would be of interest to determine whether these agents might have therapeutic benefits for conditions in which a NRHypo state may exist.

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Section: Discussionmentioning

confidence: 99%

Antiepileptic drugs and agents that inhibit voltage-gated sodium channels prevent NMDA antagonist neurotoxicity

et al. 2002

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“…Riluzole (5,41) has been demonstrated to reduce persistent sodium channel currents with greater potency than its reduction of transient peak currents in nonadapting postganglionic sympathetic neurons of the rat and mouse superior cervical ganglion (30). Riluzole was used to test the hypotheses that 1) it affects tonic firing of visceromotor neurons in the guinea pig IMG and 2) its effects are greater in neurons from inflamed guinea pigs.…”

Section: Resultsmentioning

confidence: 99%

Enhanced excitability of guinea pig inferior mesenteric ganglion neurons during and following recovery from chemical colitis

Linden

2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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Linden DR. Enhanced excitability of guinea pig inferior mesenteric ganglion neurons during and following recovery from chemical colitis. Am J Physiol Gastrointest Liver Physiol 303: G1067-G1075, 2012. First published September 6, 2012 doi:10.1152/ajpgi.00226.2012.-Postganglionic sympathetic neurons in the prevertebral ganglia (PVG) provide ongoing inhibitory tone to the gastrointestinal tract and receive innervation from mechanosensory intestinofugal afferent neurons primarily located in the colon and rectum. This study tests the hypothesis that colitis alters the excitability of PVG neurons. Intracellular recording techniques were used to evaluate changes in the electrical properties of inferior mesenteric ganglion (IMG) neurons in the trinitrobenzene sulfonic acid (TNBS) and acetic acid models of guinea pig colitis. Visceromotor IMG neurons were hyperexcitable 12 and 24 h, but not 6 h, post-TNBS during "acute" inflammation. Hyperexcitability persisted at 6 days post-TNBS during "chronic" inflammation, as well as at 56 days post-TNBS when colitis had resolved. In contrast, there was only a modest decrease in the current required to elicit an action potential at 24 h after acetic acid administration. Vasomotor neurons from inflamed preparations exhibited normal excitability. The excitatory effects of XE-991, a blocker of the channel that contributes to the M-type potassium current, and heteropodatoxin-2, a blocker of the channel that contributes to the A-type potassium current, were unchanged in TNBS-inflamed preparations, suggesting that these currents did not contribute to hyperexcitability. Riluzole, an inhibitor of persistent sodium currents, caused tonic visceromotor neurons to accommodate to sustained current pulses, regardless of the inflammatory state of the preparation, and restored a normal rheobase in neurons from TNBS-inflamed preparations but did not alter the rheobase of control preparations, suggesting that enhanced activity of voltage-gated sodium channels may contribute to colitis-induced hyperexcitability. Collectively, these data indicate that enhanced sympathetic drive as a result of hyperexcitable visceromotor neurons may contribute to small bowel dysfunction during colitis. intracellular electrophysiology; postganglionic sympathetic; inflammation INFLAMMATION OF THE GASTROINTESTINAL tract is associated with numerous changes in the neuromuscular apparatus. Within the region of inflammation, there is generally smooth muscle hyperplasia with reduced contractility (11,20,43,45,47), enhanced excitability of intrinsic primary afferent neurons (32,33,46), and neuronal cell loss (12,31). In addition to neuromuscular plasticity within the region of inflammation, there are often changes in neuromuscular function outside this area. These include reduced small bowel motility or intestinal secretory dysfunction during localized colitis in humans (2,9,35,37,48,58) and in experimental models (3,4,10,23,24,44). Systemic inflammatory cytokines or other endocrine signals may directly stimulate the upper bow...

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“…Riluzole (2-amino-6-trifluoromethoxy benzothiazole), a Na + channel blocker reported to be an antagonist of the excitatory amino acid neurotransmission (Mizoule et al, 1985), is currently used in the therapy of patients with amyotrophic lateral sclerosis (Jackson et al, 2002). Riluzole alleviates the circling behaviour in 6-OHDA-treated rats and decreases the suppression of striatal and nigral dopamine metabolism (Barneoud et al, 1996).…”

Section: Glutamate Antagonistsmentioning

confidence: 99%

Driving GDNF expression: The green and the red traffic lights

Saavedra

Baltazar

Duarte

2008

Progress in Neurobiology

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2-Amino-6-trifluoromethoxy benzothiazole, a possible antagonist of excitatory amino acid neurotransmission—I

Cited by 172 publications

References 24 publications

Antiepileptic drugs and agents that inhibit voltage-gated sodium channels prevent NMDA antagonist neurotoxicity

Antiepileptic drugs and agents that inhibit voltage-gated sodium channels prevent NMDA antagonist neurotoxicity

Enhanced excitability of guinea pig inferior mesenteric ganglion neurons during and following recovery from chemical colitis

Driving GDNF expression: The green and the red traffic lights

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