Toxicological study of a new maintenance fluid, Veen 3G, in rats.

A study of the different volume and infusion rates of a new maintenance fluid, Veen 3G, on the general conditions of rats was investigated during the 14 days after infusion. In Experiment I, 100 ml/kg and 200 ml/kg of Veen 3G were infused at a rate of 300 ml/kg/h in male and female rats. Results were compared with those for Gurunon Ringer solution (GRS) in male and female rats. We observed only transient polyuria in animals administered by each dose of Veen 3G and GRS for 0-15 min after infusion. Necropsy was not observed in any of the animals tested 14 days after infusion. In Experiment II, 200 ml/kg of Veen 3G was infused at rates of 200, 400, 800 and 1600 ml/kg/h in male rats. At 800 and 1600 ml/kg/h, irregular respiration and decrease in movement were observed concomitantly with polyuria. Three out of 4 rats died immediately after the infusion of Veen 3G at a rate of 1600 ml/kg/h, and one rat was still alive 14 days after the infusion. In this experiment, 200 ml/kg Veen 3G was safe when we infused at a rate of less than 400 ml/kg/h in male rats. Since this rate is about 27-80 times higher than that used clinically in maintenance treatment, Veen 3G is suggested to be safe, with the exception of polyuria, in clinical situations at the standard infusion rate (5-15 ml/kg/h).

Ipidacrine (NIK-247), a novel antidementia, rapidly enters the brain and improves scopolamine-induced amnesia in rats during the Morris water maze task.

The effects of single and repeated administrations of ipidacrine (NIK-247, 9-amino-2, 3, 5, 6, 7, 8-hexahydro-1H-cyclopenta [b] quinoline monohydrochloride monohydrate) on scopolamine-induced spatial learning deficit were investigated in rats using the Morris water maze task. A single oral administration of ipidacrine (0.3 and 1 mg/kg) reduced the increased total latency induced by scopolamine in this task. The repeated administration of ipidacrine (1 mg/kg) of once a day for 5 successive days reduced the increased total latency induced by scopolamine to the levels of the saline-treated control rats in this task. In this pharmaco-kinetic study, ipidacrine was rapidly taken up into the brain within 5 min. Moreover, higher drug levels were observed mainly in the cortex and hippocampus, which both play important roles in learning and memory. Thus, a previous study together with this investigation indicate that ipidacrine improves amnesia which consists of the impairment of the working and reference memory in various animal models, suggesting that ipidacrine is a useful candidate for the therapy of patients with Alzheimer's disease.