抄録
Action of morphine on the blood sugar level had previously been described in the voluminous literatures and the mechanism of hyperglycemic action had widely been known to be a central stimulation in the posterial hypothalamus, to increase adrenal epinephrine secretion (l-4). E. Larson (5) reported that methadone, dromoran and meperidine produced hyperglycemia in rabbits and rats. He, however, had mentioned in the same report that not a few rats, which were administered with 25-50 mg/kg of morphine in his experiment, died under hypoglycemia.
The action mode of hypoglycemia produced by morphine had never been investigated, since the studies on this action was found very difficult on account of overlapping with hyperglycemic response in animals produced by morphine itself. It is consequent that the morphine-derivatives showing purely hypoglycemic effect without any hyperglycemic responses is expected to be synthetized as an experimental materials. 4-Dimethylamino-n-methyl-2, 2-diphenyl valeramide hydrochloride (U-6420), which's chemical structure was related with that of methadone, was reported as a hypoglycemic agent by Dulin et al. (6) and was recently found to have an additive effect on morphine-hypoglycemia (7). It seemed expectable that if the compound mentioned above would have the similar action-mechanism to the morphine's one, some active compounds might be discovered in the group of derivatives from methadone, since these reports told us that the toxic dose (respiration arrest) of U-6420 was near to its effective level.
Present communication described the results of screening test for 3 and/or 4 substitutes of N-methyl piperidines and the actions of the derivatives of 3-aza bicyclo 3, 3, 1 nonane screened by our experiments.
