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.

Abstract

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.

• Authors: Y Kunoh, H Ogawa, M Nagasaka, H Asai, A Iguchi, A Niki, N Sakamoto
• Journal: Archives internationales de pharmacodynamie et de therapie (Arch Int Pharmacodyn Ther) 1989 Mar-Apr Vol. 298 Pg. 276-87 ISSN: 0003-9780 [Print] Belgium
• PMID: 2667487 (Publication Type: Journal Article)

Chemical References

• Hypoglycemic Agents
• Insulin
• Liver Glycogen
• Pyrimidines
• MTP 1307
• Glucose

Topics

• Adipose Tissue (drug effects, metabolism)
• Animals
• Diabetes Mellitus, Experimental (metabolism)
• Gluconeogenesis (drug effects)
• Glucose (metabolism)
• Glucose Tolerance Test
• Hypoglycemic Agents (pharmacology)
• Insulin (metabolism)
• Insulin Secretion
• Liver (drug effects, metabolism)
• Liver Glycogen (biosynthesis)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Obese
• Pyrimidines (pharmacology)
• Rats
• Rats, Inbred Strains