[General pharmacology of (2"R)-4'-O-tetrahydropyranyladriamycin, a new antitumor antibiotic].
General pharmacology of (2"R)-4'-O-tetrahydropyranyladriamycin hydrochloride (THP) was studied in experimental animals. Intravenous administration of THP showed no significant effect on the respiratory and cardiovascular systems, such as blood pressure, heart rate, ECG and respiration in anesthetized rabbits and dogs. But in rats and cats, THP produced a transient decrease in blood pressure resulted from vasodilation. The hypotension was not inhibited by antihistaminics. Contraction of isolated guinea-pig atria was stimulated by THP at high concentrations (10(-4) g/ml). THP inhibited the spontaneous movement of isolated rabbit ileum and rat uterus (virgin and pregnant) at high concentrations (10(-4) g/ml). In some isolated guinea-pig ileum preparations, THP partially (6 approximately 36%) antagonized the contraction inducing by acetylcholine, histamine, serotonin and barium chloride. Urine volume and urinary excretion of electrolytes were increased by intravenous injection of 5.0 mg/kg THP. Vascular permeability was progressed when administered intracutaneously. Hemolytic effect was shown at high concentrations (10(-4) g/ml) but no effect on the coagulation was found. No significant effect of THP was observed on the general behavior and central nervous system, autonomic nervous and peripheral nervous systems. Also, THP had no significant effect on gastrointestinal propulsion in mice, the mucous membranes of the stomach and duodenum of rats, or gastric acid and bile secretion in rats.
Tone
H
H
Kiyosaki
T
T
Nishimori
T
T
Kobayashi
F
F
Nishimura
K
K
Morino
H
H
Tsuchiyama
M
M
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001341:Autonomic Nervous System / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D002415:Cats; D002490:Central Nervous System / Q000187:drug effects; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010525:Peripheral Nerves / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D012119:Respiration / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; C027260:pirarubicin