In this study, we examined the effect of noradrenaline on delayed neuronal death induced by chemical ischemia, a model of ischemia-reperfusion injury in vivo, in the mixed culture of human astrocytoma U-251 MG cells and human neuroblastoma SH-SY5Y cells. Chemical ischemia was induced by incubating the cultures in buffered salt solution containing 0.5 mM 2-deoxy-D-glucose and 5 mM sodium azide for 3 hours. After the induction of chemical ischemia, the medium was replaced with DMEM and cultured for an additional 45 hours. Delayed neuronal cell death of SH-SY5Y cells after chemical ischemia was significantly attenuated by noradrenaline (3 μM) in the mixed culture, but not in single culture of SH-SY5Y cells. The neuroprotective effect of noradrenaline was inhibited by a nonselective α-adrenoceptor antagonist phenoxybenzamine (3 μM), but not by a nonselective β-adrenoceptor antagonist propranolol (10 μM), whereas a selective α₁-adrenoceptor agonist phenylephrine (1-30 μM) attenuated chemical ischemia-induced cell death of SH-SY5Y cells in the mixed culture. These results suggest that noradrenaline attenuates chemical ischemia-induced delayed cell death of SH-SY5Y cells by stimulating the α₁ receptor of U-251 MG cells in the mixed culture.