Safety pharmacology of CKD-602, a novel anticancer agent.
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.
Kim
Eun Joo
EJ
Toxicology Research Center, Korea Research Institute of Chemical Technology, Yuseong, Daejeon, Korea.
Lee
Rae Kyong
RK
Suh
Jeong Eun
JE
Han
Sang Seop
SS
Kim
Joon Kyum
JK
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
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