Abstract

The effect of morphine, meperidine, methadone, dextromoramide and levorphanol on the biliary flow through the terminal bile duct in situ has been studied in the cat and dog. These drugs were also tested on the isolated bile duct of calf and cat. The bile duct in situ was considerably more sensitive to these drugs than was the isolated bile duct. The order of potency in constricting the terminal bile duct is the following: on the isolated bile duct, meperidine > levorphanol > morphine; and in situ, dextromoramide > levorphanol > morphine > methadone > meperidine.

The constriction of the bile duct can be dissociated from the increased motility of the duodenum. Except for meperidine, all the drugs exhibit tachyphylaxis.

The mechanism of action of the analgesic drugs on the bile duct was investigated, with the following findings: (a) their actins were not antagonized by drugs blocking acetylcholine, epinephrine and norepinephrine, histamine and 5-hydroxytryptamine: (b) the constrictor action of the analgesics was greater when injected intravenously than when infused intraarterially to the eholedoehus-duodenal junction; (c) the isolated bile duct bathed by exteriorized blood of a donor eat was as sensitive as the bile duct in situ in the donor cat to intravenous injection of of morphine: (d) the response of the bile duct were unaffected after severing all nervous connections and after hexamethonium; (e) the analgesics had no effect on the response of the bile duct to stimulation of autonomic nerves.

It is suggested that the constriction of the bile duct in situ after giving time analgesic drugs is due to the liberation of a constrictor substance, The constriction of the isolated bile duct caused by the analgesic drugs may be due to their action directly on the smooth muscle.