Action of anti-tussive drugs on the emetic reflex of Suncus murinus (house musk shrew).
The cough and emetic reflexes involve a synchronized firing of motor neurones involved in respiratory control. Tachykinin NK1 receptor antagonists and 5-HT1A receptor agonists are examples of centrally acting drugs that reduce cough and emesis. In the present studies, therefore, we examined the possibility that other classes of drugs known to reducing cough have anti-emetic properties to prevent emesis induced by diverse challenges. We examined the potential of codeine (1-10 mg/kg), baclofen (1-10 mg/kg), scopolamine (0.3-10 mg/kg), diphenhydramine (1-10 mg/kg), imperialine (1-30 mg/kg) and verticine (0.3-3 mg/kg) to inhibit emesis induced by nicotine (5 mg/kg, s.c.), copper sulphate (120 mg/kg, intragastric), and provocative motion (4 cm horizontal displacement, delivered at 1 Hz) in Suncus murinus (house musk shrew). Only codeine had broad inhibitory properties (P<0.05) to antagonize emesis induced by all challenges with ID50 values ranging from 1.2 to 2.3 mg/kg. Baclofen antagonized emesis induced by nicotine (maximum reduction was 44.9%, P<0.05) and motion (maximum reduction was 97.3%, P<0.01), but potentiated copper sulphate-induced emesis (maximum potentiation was 73.0%, P<0.05). Scopolamine antagonized copper sulphate-induced emesis (maximum reduction was 61.2%, P<0.05) and imperialine antagonized nicotine-induced emesis (maximum reduction was 30.2%, P<0.01), but verticine potentiated motion-induced emesis (maximum potentiation was 60.0%, P<0.05). Diphenhydramine did not significantly reduce emesis induced by any of the challenges (P>0.05). In conclusion, codeine has broad inhibitory anti-emetic actions but a known ability to reduce coughing does not necessarily predict broad inhibitory anti-emetic properties.
Chan
Shun-Wan
SW
Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
Rudd
John A
JA
Lin
Ge
G
Li
Ping
P
D000704:Analysis of Variance; D000818:Animals; D000932:Antiemetics / Q000494:pharmacology* / Q000627:therapeutic use; D000996:Antitussive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001418:Baclofen / Q000494:pharmacology; D002595:Cevanes / Q000494:pharmacology; D003061:Codeine / Q000494:pharmacology; D019327:Copper Sulfate; D004155:Diphenhydramine / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D009041:Motion Sickness / Q000503:physiopathology / Q000517:prevention & control*; D009538:Nicotine; D012018:Reflex / Q000187:drug effects*; D012601:Scopolamine / Q000494:pharmacology; D012788:Shrews; D014839:Vomiting / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*
D000932:Antiemetics; D000996:Antitussive Agents; D002595:Cevanes; C014242:verticine; D009538:Nicotine; D004155:Diphenhydramine; D012601:Scopolamine; D001418:Baclofen; D019327:Copper Sulfate; D003061:Codeine