5-Iodo-A-85380, a specific ligand for α4β2 nicotinic acetylcholine receptors, prevents glutamate neurotoxicity in rat cortical cultured neurons

Masashi Ueda, Yasuhiko Iida, Youji Kitamura, Hidekazu Kawashima, Mikako Ogawa, Yasuhiro Magata, Hideo Saji

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16 Citations (Scopus)


5-iodo-3-(2(S)-azetidinylmethoxy)pyridine (5-iodo-A-85380, 5IA) has very high affinity and selectivity to nicotinic acetylcholine receptor (nAChR) α4β2 subtype, and a relative safe profile. To assess whether 5IA has neuroprotective properties, we examined the effect of 5IA on glutamate (Glu)-induced neurotoxicity using primary cultures of rat cortical neurons. A 10-min exposure of cultures to Glu followed by 2-h incubation with drug-free medium caused a marked loss of viability, as determined by trypan blue exclusion method. Glu-induced neurotoxicity was prevented by 5IA both in a time- and concentration-dependent manner. 5IA-induced neuroprotection required pretreatment of 5IA prior to Glu exposure with an optimal concentration of 10 nM and an optimal pretreatment time of 2 h. Treatment after Glu exposure could not rescue the cultured cells. The neuroprotective effect of 5IA was antagonized by mecamylamine, a nAChR antagonist, but not by scopolamine, a muscarinic acetylcholine receptor antagonist. Dihydro-β-erythroidine, an α4β2 nAChR antagonist, completely inhibited 5IA-induced neuroprotection, whereas α-bungarotoxin, an α7 nAChR antagonist, had no effect. Furthermore, 5IA did not show neuroprotective effects in the absence of extracellular Ca2+. These results suggest that the neuroprotective effects of 5IA are produced by activation of α4β2 nAChRs followed by the influx of extracellular Ca2+. In conclusion, 5IA is possibly not only useful for the treatment and prevention of glutamate neurotoxicity, but also as an available tool for elucidating the mechanism of neuroprotection associated with α4β2 nAChRs.

Original languageEnglish
Pages (from-to)46-52
Number of pages7
JournalBrain Research
Publication statusPublished - Mar 14 2008
Externally publishedYes


  • 5-iodo-A-85380 (5IA)
  • Extracellular calcium ion
  • Glutamate toxicity
  • Neuroprotection
  • Nicotinic acetylcholine receptor
  • α4β2 subtype

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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