Absence of emetic effects of morphine and loperamide in Suncus murinus.
The house musk shrew Suncus murinus recently has been introduced for the study of emesis. We investigated the emetic effects of the opioids morphine (0.1-21.5 mg/kg i.p.) and loperamide (0.01-10 mg/kg i.p.) and found a complete lack of emetogenic potential. Nicotine, however, dose dependently induced vomiting in the Suncus with an ED50 of 8.8 mg/kg s.c. and a 100% incidence at 20 mg/kg. This drug-induced vomiting was reduced by morphine or loperamide: ED50 values obtained were 1.2 mg/kg i.p. for morphine and 0.7 mg/kg i.p. for loperamide. Naloxone (2 mg/kg s.c.) antagonised the inhibitory effect of morphine (2 mg/kg i.p.) or loperamide (10 mg/kg i.p.). Serotonin (20 mg/kg s.c.) had less reliable emetogenic potency than nicotine in the Suncus with incidences between 50 and 100%. However, the serotonin-induced vomiting was abolished by morphine and loperamide and this inhibition was antagonised by naloxone. These results suggest that systemically administered opioids are pure antiemetics in Suncus murinus in contrast to other animal models and man. Naloxone antagonism indicates that this antiemetic effect is mediated by opioid receptors.
Selve
N
N
Abteilung Pharmakologie, Grünenthal GmbH, Aachen, Germany.
Friderichs
E
E
Reimann
W
W
Reinartz
S
S
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008139:Loperamide / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D008297:Male; D009020:Morphine / Q000627:therapeutic use*; D009270:Naloxone / Q000494:pharmacology; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D012701:Serotonin / Q000633:toxicity; D012702:Serotonin Antagonists / Q000494:pharmacology; D012788:Shrews; D014839:Vomiting / Q000139:chemically induced* / Q000517:prevention & control*
D012702:Serotonin Antagonists; D012701:Serotonin; D009270:Naloxone; D009538:Nicotine; D008139:Loperamide; D009020:Morphine