1977 Volume 2 Issue 2 Pages 115-127
Tolerance was provoked to all the pharmacological activities of H-88 examined, such as anti-inflammatory (Carrageenin-induced rat paw edema), analgetic (Tail pressure method in mice), hypothermic (Rectal temperature in mice), hypomotor activity (Wheal cage method in mice), prolongation of the sleeping time induced by pentobarbital Na (rats and mice), depression of gastric emptying and intestinal transport (rats) and stimulation to hypothalmo-hypophyse-adrenal axis (rats). The effect of H-88 on the pentobarbital Na-induced sleeping time in rats was not dissipated by adrenalectomy, and did not depend on the depression of intestinal absorption. The development of tolerance to H-88 was antagonized by ethionine pretreatment. It is suggested that tolerance to H-88 is mainly due to the hepatic enzyme induction.
