Moranoline (1 -deoxynojirimycin) isolated from mulberry root bark (Mori Cortex), is a potent intestinal a-glucosidase inhibitor. The IC50 values for sucrase and maltase in various animals ranged around 10~7m.Postprandial hyperglycemia in sucrose-, starch-, or maltose-loaded rats was significantly supressed by simultaneous administration of moranoline in doses over 6 mg/kg. In contrast to the potent inhibition of intestinal a-glucosidase, the inhibition of /?-glucosidase, glucoamylase, and a-amylase was weak.Among the N-substituted alkyl derivatives of moranoline, the methyl and ethyl derivatives had more potent hypoglycemic activity than moranoline in sucrose-or starch-loaded rat models. Nojirimycin, or 2,5-dihydroxymethyl 3,4-dihydroxypyrrolidine (DMDP), which structurally re-

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The effects of 4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy) pyrimidine hydrochloride (NS-7), a novel neuroprotective compound, on the voltage-sensitive sodium channels (VSSC) were examined in the rat brain and cardiac myocytes. NS-7 inhibited [3H]batrachotoxinin A 20 alpha-benzoate (BTX) binding (neurotoxin receptor site 2) in brain membranes with a Ki value of 1 microM, while the compound was less effective in the cardiac myocytes (Ki = 13 microM). Aconitine, on the other hand, inhibited [3H]BTX binding to brain membranes and cardiac myocytes with the same potency. In contrast. NS-7 had no affinity for [3H]saxitoxin binding in brain (neurotoxin receptor site 1). In superfused slices of the rat cerebral cortex, NS-7 inhibited the veratridine (5 microM)-evoked glutamate release in a concentration-dependent manner, the IC50 value of which was 7.7 microM, whereas the compound showed a weak and not significant suppression of KCl-evoked glutamate release. The tissue concentrations of NS-7 in the rat cerebral cortex and heart were 89 and 28 nmole/g tissue, respectively, 5 min after its intravenous injection (8 mg/kg). Furthermore, in the cerebral cortex, NS-7 distributed preferentially to the membrane-enriched synaptosomal fraction. Since neurotoxin receptor site 2 is located in the transmembrane region of the VSSC moiety, the channel function may be substantially inhibited by a peripheral administration of NS-7. These results suggest that the blockade of neurotoxin receptor site 2 of VSSC in the brain contributes to the neuroprotective action of NS-7.

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Preischemic treatment with MOR-14 preserved glycogen, attenuated the accumulation of lactate, and reduced the myocardial infarct size by 69%. This cardioprotective effect was independent of changes of blood pressure and heart rate or regional blood flow. It may be associated with alpha-1,6-glucosidase inhibition, because MOR-14 markedly decreased the alpha-1,6-glucosidase activity in the heart.