title: Safety pharmacology of CKD-602, a novel anticancer agent.
abstract: CKD-602 ((20S)-7-[2-(N-isopropylamino)-ethyl]-camptothecin.HCl, CAS 213819-48-8) is a new class of anticancer drug that belongs to the topoisomerase inhibitors. Its effect on the central nervous system (CNS), general behavior, cardiovascular-respiratory system and the other organ systems were studied. When intravenously administered, CKD-602 up to doses of 5 mg/kg caused an increase of body temperature, increase of respiration rate, decrease of gastrointestinal transport, showed analgesic action and produced antisecretory action in pylorus ligated rats. However, CKD-602 showed no effects on general behavior, motor coordination, spontaneous locomotor activity, hexobarbital sleeping time, convulsion, cardiovascular, smooth muscle and urinary tract system. These findings demonstrate that CKD-602 in doses up to 5 mg/kg has minor effects on the CNS in animals. However, CKD-602 does not exert any general pharmacological effects at the dose of 1 mg/kg except the effects on gastric secretion.
authors.affiliation: Toxicology Research Center, Korea Research Institute of Chemical Technology, Yuseong, Daejeon, Korea.
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Kim
authors.forename: Rae Kyong
authors.initials: RK
authors.lastname: Lee
authors.forename: Jeong Eun
authors.initials: JE
authors.lastname: Suh
authors.forename: Sang Seop
authors.initials: SS
authors.lastname: Han
authors.forename: Joon Kyum
authors.initials: JK
authors.lastname: Kim
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000633:toxicity*; D004285:Dogs; D004791:Enzyme Inhibitors / Q000633:toxicity; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006591:Hexobarbital / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015656:Respiratory Mechanics / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D012890:Sleep / Q000187:drug effects; D059004:Topoisomerase I Inhibitors
chemical_list: D000700:Analgesics; D000927:Anticonvulsants; D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D006993:Hypnotics and Sedatives; D059004:Topoisomerase I Inhibitors; C116963:belotecan; D006591:Hexobarbital; D002166:Camptothecin