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1. Administration of diquat (NN'-ethylene-2,2'-bipyridilium) or paraquat (NN'-dimethyl-4,4'-bipyridilium) prevents the normal depletion of liver glycogen in starved rats. 2. There is an increase in blood glucose, which returns to normal values after approx. 7h. 3. After administration of diquat or paraquat, plasma corticosteroids increase to very high concentrations and remain high for at least 24h, but plasma ACTH (adrenocorticotrophin) is only increased for 4h. 4. Adrenal cyclic AMP is considerably increased after administration of diquat and remains significantly higher than control values for at least 24h. 5. It is suggested that diquat and paraquat increase the response of the adrenal cortex to ACTH.

Previous studies suggest that proteoglycans and glycosaminoglycans (GAGs) may play an important role in the pathogenesis and/or alleviation of neurodegenerative disorders, including Alzheimer’s disease (AD). Proteoglycans increase the formation of neurofibrillary tangles, and stimulate the aggregation of β-amyloid (Aβ). This effect, on the other hand, is believed to be competitively inhibited by certain GAGs. Over the past few years, we have examined the neuroprotective properties of Neuroparin (C3), a low-molecular-weight GAG (approx. 2.1 kDa), in animal models of lesions characteristic of AD. Neuroparin is composed of 4–10 oligosaccharides, and it is derived from heparin involving depolymerization of heparin by gamma irradiation. In our experiments, Neuroparin protected against cholinergic lesions induced by intracerebroventricular injection of a specific cholinotoxin, AF64A, in rats. Administration of Neuroparin attenuated AF64A-stimulated, low-affinity nerve growth factor receptor-immunoreactive axonal varicosities in the rat septum, and increased arborization of hippocampal CA1 neurons. Neuroparin also reduced the septal caspase 3 immunoreactivity induced by AF64A treatment. Moreover, Neuroparin reduced tau 2 immunoreactivity in the rat hippocampus, stimulated by intra-amygdaloid injection of Aβ_25–35. These findings are in good agreement with our previous data indicating a neuroprotective role of GAGs. These results, plus others, all suggest that Neuroparin may possess neuroprotective properties against many of the characteristic neural lesions in AD. Since our pharmacokinetic studies revealed that Neuroparin is capable of crossing the blood-brain barrier, Neuroparin may, conceivably, open an entirely new avenue in the treatment of neurodegenerative disorders. Phase I studies have been completed, and have proven to be extremely supportive in that regard.