Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Morphine slows hepatobiliary elimination of sulfobromophthalein in rodents, raising dye levels in plasma and liver. Earlier studies showed these effects to be independent of other opiate effects such as bile duct spasm, hypothermia or blood gas changes resulting from respiratory depression. Because opiate receptors are distributed throughout the body, within the central nervous system and at peripheral sites including the gastrointestinal tract, experiments were performed to ascertain whether central or peripheral sites mediate the hepatobiliary effects of morphine. Sulfobromophthalein was administered intravenously to mice and its levels were measured in plasma and liver. Tail-flick latency indicated centrally mediated analgesia. Inhibited intestinal transit of India ink reflected an opiate effect with a significant peripheral component. When injected into a cerebral ventricle morphine was much more potent in producing analgesia and raising sulfobromophthalein levels than when administered intravenously or intraperitoneally. An intravenous dose of naloxone that reversed morphine analgesia also prevented sulfobromophthalein elevation but did not prevent gut slowing. Naltrexone injected in a cerebral ventricle also reversed analgesia and sulfobromophthalein elevation but not intestinal slowing. The polar opiate agonist N-methylmorphine did not cause analgesia or raise sulfobromophthalein levels at peripheral intraperitoneal doses to 100 mg/kg. When given in a central ventricle at 4 x 10(-3) mg/kg, this agent produced analgesia and raised sulfobromophthalein but did not slow intestinal transit. After spinal cord transection, intravenous morphine did not retard the tail-flick response or affect sulfobromophthalein disposition, but peripherally mediated intestinal transit was slowed as it was in intact mice. These experiments demonstrate parallel opiate effects on analgesia and on BSP disposition but not on intestinal transit.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Hepatobiliary effects of morphine are mediated in the brain. 217 93

Loperamide effects on hepatobiliary function, analgesia and gut transit were studied in mice. Varying doses of the antidiarrheal drug, loperamide, were administered to mice by intracerebroventricular, intravenous, subcutaneous and intragastric routes. Gut motility was determined by intestinal transit of India ink, analgesia by warm water tail flick latency, and hepatobiliary function by retention of the anionic dye, sulfobromophthalein in plasma and liver. When given by all routes at modest doses, loperamide slowed intestinal transit. Analgesia, a centrally mediated opiate effect, was only detected after intracerebroventricular or subcutaneous loperamide at high, near-toxic doses. Elevations of plasma and liver sulfobromophthalein were noted at routes and doses which slowed gut transit, well below those needed for analgesia. Intragastric loperamide at one fortieth its LD50 caused marked elevation of sulfobromophthalein levels and gut slowing, but no analgesia. Sulfobromophthalein elevation and gut slowing by intragastric loperamide were not affected by spinal cord transection but were reversed by naltrexone, an opiate antagonist. Non-toxic doses of loperamide slow gut transit and modify hepatobiliary function in mice by opiate actions at peripheral sites.
 ...
PMID:Loperamide effects on hepatobiliary function, intestinal transit and analgesia in mice. 817 10