Abstract:
:Many anti-epileptic drugs (AEDs) that mainly target ion channels or post-synaptic receptors are in clinical use, but a proportion of patients are resistant to these traditional AEDs and experience repeated severe break-out seizures. Given its involvement in the etiology of epilepsy, the neurotransmitter glycine may serve as a novel target for epilepsy treatment. Increasing evidence suggests that inhibitors of glycine transporter 1 (GlyT1) exhibit anti-seizure properties in mouse models and show potential as anti-convulsions drugs. In the present study, we investigated the effect of a highly selective GlyT1 inhibitor (named M22) on glycine transport kinetics using a radioactive substrate uptake assay and investigated the anti-seizure effects of M22 on the maximal electroshock seizure threshold (MEST) test and the timed intravenous (i.v.) pentylenetetrazole (PTZ) intravenous test. Our results demonstrate that M22 was capable of elevating the seizure threshold in the MEST test but did not alter the seizure threshold in the PTZ i.v. test. Strychnine, an inhibitor of glycine receptor activity, reversed the threshold elevation at a subconvulsive dosage (0.1 mg/kg subcutaneously) in the MEST test and did not affect M22 plasma levels in mice, suggesting that the anti-seizure effect in this model may be mediated by increased glycine receptor activity. Moreover, M22 administration did not influence motor function and coordination in mice. In combination with the previously reported excellent pharmacokinetic features of M22, our present results suggested that M22 has the potential to serve as a new anti-convulsive drug or as a lead compound for the development of AEDs.
journal_name
Biol Pharm Bulljournal_title
Biological & pharmaceutical bulletinauthors
Zhao J,Tao H,Xian W,Cai Y,Cheng W,Yin M,Liang G,Li K,Cui L,Zhao Bdoi
10.1248/bpb.b15-00501subject
Has Abstractpub_date
2016-01-01 00:00:00pages
174-80issue
2eissn
0918-6158issn
1347-5215journal_volume
39pub_type
杂志文章abstract::Swallowing involves several motor processes such as bolus formation and intraoral transport of a food bolus (oral stage) and a series of visceral events that occur in a relatively fixed timed sequence but are to some degree modifiable (pharyngeal stage or swallow reflex). Reflecting the progressive aging of society, p...
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pub_type: 杂志文章,评审
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journal_title:Biological & pharmaceutical bulletin
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journal_title:Biological & pharmaceutical bulletin
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journal_title:Biological & pharmaceutical bulletin
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pub_type: 杂志文章,多中心研究,随机对照试验
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journal_title:Biological & pharmaceutical bulletin
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journal_title:Biological & pharmaceutical bulletin
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journal_title:Biological & pharmaceutical bulletin
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journal_title:Biological & pharmaceutical bulletin
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journal_title:Biological & pharmaceutical bulletin
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