Pharmacological studies on “rhodotoxin” isolated from rhododendron hymenanthes and “andro medotoxin” isolated from andromeda japonica, thunberg

Abstract

1. In chemical characters of rhodotoxin (RTR) and andromedotoxin (ATA) isolated from Andromeda japonica, they have similar reactions against several reagents, but m.p. 120-119�C in ATA, 258-260'C in RTR, and Rf-value of paperchromatograms is 0.89 in ATA, 0.96 in RTR. 2. LD50 on mice (subcutaneously) is 3.473-�0.132 ug'g in ATA, and 0.143�0.01,ug,!g in RTR. The toxicity on mice of RTR is 23.4 times that of ATA. LD50 on Rana nigromaculata (into lymphsack) is 5.074-�0.66,ug/g in ATA, and 3.899�-0.125,ug/g in RTR. The toxicity on frogs of RTR is 1.3 times that of ATA. MLD on cats and rabbits anesthetized with urethane (intravenously) is about 400,ug/kg in both ATA and RTR, the time of death after administration is from 7 to 28 min. The cause of death is respiratory paralysis in all cases. 3. The emetic action on cats of RTR (subcutaneously) occurs from 80 pg/kg, and the dose which causes vomiting in 50 per cent of cases of that animal (ED50) is 83.3�0.8 ug/kg ; the action of ATA occurs from 70 ug/kg, and its ED50 is 123.3:L-15.2 ug/kg. The emetic action of RTR is 1.47 times that of ATA. ED50 on Rana nigromaculata (into lymphsack) is 0.347�0.026 ug/g in RTR, and 1.180� 0.120,ug/g. The emetic action on frogs of RTR is 3.4 times that of ATA. So-called frog's mouth-opening corresponding with mammal's nausea, occurs from 0.25,ug/g, and always from 0.59 to 5.5 ug/g with a few exceptions, in RTR. Its action occurs from 0.125,ug/g in ATA, and invariably from 1.3 to 10 pg'g with a few exceptions. 4. The vasodepressor action in anesthetized cats by the administration of 20,ug/kg of RTR reduces by 41.8,?,ot'h e normal blood pressure, with recovery to 64.5, 74.6, 76.8 and 80% of normality, respectively in 15, 30, 45 and 60 min. The administration of 20,ug/kg of ATA diminishes by 78.3% the normal blood pressure, and recovery to 93.6, 97.5, 100 and 100% of usual state occurs respectively in 15, 30, 45 and 60 min. In rabbits the administration of 20 ug/kg of RTR reduces by 39.5 Jo : the normal blood pressure, and recovery to 50.3, 70.7, 80.8 and 89.8!0 of normal, respectively follows in 15, 30, 45 and 60 min. The same dose of ATA reduces normal blood pressure by 62.2%, with recovery to 76.2, 88.0, 91.6 and 93.7% of usual state respectively in 15, 30, 45 and 60 minutes. From the above results, it is confirmed that RTR (rhodotoxin) and ATA (andromedotoxin isolated from Andromeda japonica) are different substances. © 1956, The Japanese Pharmacological Society. All rights reserved.