Effects of double-enkephalin (biphalin), an enkephalin analogue, on respiration and the cough reflex in rats

The pharmacological actions of double-enkephalin (biphalin; (HCl-Try-D-Ala-Gly-Phe-NH-)2) an analogue of enkephalin, on nociception, respiration and the cough reflex were compared with those of morphine in anesthetized rats. Double-enkephalin (D-Enk), injected i.p., produced significant analgesia at doses of 10 and 20 mg/kg in a hot-plate test. The analgesic effect of D-Enk was antagonized by pretreatment with naloxone (5 mg/kg, i.p.). D-Enk and morphine (M) produced a dose-dependent decrease in the frequency of respiration (RF) and in the tidal volume (Vt). However, the effects of D-Enk on RF and Vt were significantly weaker than those of M. The 50% antitussive dose (AtD50) of D-Enk and M were 0.63 and 0.48 mg/kg, i.p., respectively. The antitussive effect of D-Enk was antagonized by pretreatment with naloxone (0.4 mg/kg, i.p.). These results suggest that D-Enk exerted an antitussive effect similar to that of morphine, and that the involvement of opiate receptors is associated with the antitussive effect of D-Enk.