Pharmacological studies on the hypoglycemic effect of 7,8-dihydro-2- (4-methylpiperazinyl) -4- (1-pyrrolidinyl) -6H-thi opyrano [3,2-d] pyrimidine dimaleate (MTP-1307) , a novel hypoglycemic agent
Kunoh, Y.; Ogawa, H.; Nagasaka, M.; Asai, H.; Iguchi, A.; Niki, A.; Sakamoto, N.
Archives Internationales de Pharmacodynamie et de Therapie 298: 276-287
1989
ISSN/ISBN: 0003-9780 PMID: 2667487 Document Number: 340562
MTP-1307, 7,8-dihydro-2-(4-methylpiperazinyl)-4-(1-pyrrolidinyl)-6H- thiopyrano[3,2-d]pyrimidine dimaleate, is a novel oral hypoglycemic agent, structurally different from any existing hypoglycemic drugs. In fasted rats, the hypoglycemic effect of MTP-1307 was accompanied by elevation of the plasma insulin. In glucose tolerance tests, MTP-1307 suppressed the hyperglycemia after glucose loading and significantly enhanced the glucose-induced insulin secretion. In isolated hepatocytes from fasted rats, MTP-1307 inhibited gluconeogenesis from lactate and alanine. Furthermore, MTP-1307 increased the lactate/pyruvate ratio but did not increase the lactate level. MTP-1307 did not influence glycogenolysis in isolated hepatocytes from fed rats. In genetically diabetic ob/ob mice, MTP-1307 decreased the blood glucose level and improved glucose tolerance, but did not affect the level of plasma insulin. MTP-1307 increased 14CO2 production from glucose in isolated epididymal fat pads of ob/ob mice. Thus, these findings suggest that MTP-1307 produces hypoglycemic activities not only in normal animals but also in genetically diabetic animals, and that the hypoglycemic mechanism of MTP-1307 involves the promotion of glucose utilization in adipose tissue and, partially, the inhibition of gluconeogenesis in the liver and the stimulation of insulin release from the pancreas.