General pharmacology of CKD-732, a new anticancer agent: effects on central nervous, cardiovascular, and respiratory system.
CKD-732 [6-O-(4-dimethylaminoethoxy) cinnamoyl fumagillol hemioxalate] is a new fumagillin anticancer drug that belongs to an angiogenesis inhibitor. Its effect on the central nervous system (CNS), general behavior, cardiovascular-respiratory system and the other organ systems were studied. CKD-732 was intravenously administered with the dosages of 10, 30, 40 or 50 mg/kg and the highest dosage of 50 mg/kg prolonged the hexobarbital-induced sleep time. CKD-732 at the dosage of 50 mg/kg, also, caused the decrease of body temperature from 15 to 120 min after the administration, which was recovered at 240 min. In the study of the effects on gastric secretion, CKD-732 induced the increase of pH and decrease of total acidity. However, CKD-732 showed no effect on general behavior, spontaneous locomotor activity, motor coordination, analgesia, convulsion, mean arterial pressure, and cardiac functions except for heart rate of isolated rat heart, respiration, isolated smooth muscle, intestinal charcoal transport and renal function. Based on the results, we suggested that CKD-732 is safe general pharmacologically at clinical supposed dose (1.75 mg/kg) and demonstrated to have much better safety than other fumagillin derivatives.
Kim
Eun-Joo
EJ
Department of Pharmacology and National Research Laboratory, Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, Yuseong, Daejeon, 305-343 Korea.
Shin
Won-Ho
WH
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002319:Cardiovascular System / Q000187:drug effects*; D002490:Central Nervous System / Q000187:drug effects* / Q000502:physiology; D002934:Cinnamates / Q000494:pharmacology*; D003510:Cyclohexanes; D004305:Dose-Response Relationship, Drug; D015507:Drugs, Investigational / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D012137:Respiratory System / Q000187:drug effects*; D012717:Sesquiterpenes / Q000494:pharmacology*
D000970:Antineoplastic Agents; D002934:Cinnamates; D003510:Cyclohexanes; D015507:Drugs, Investigational; D004852:Epoxy Compounds; D012717:Sesquiterpenes; C487952:CKD732