Analgesic,central, cardiovascular and endocrine effects of the enkephalin analogue Tyr-D.Arg-Gly-Phe(4NO2)-Pro-NH2 (443C81) in healthy volunteers

Summary 443C81 is a synthetic enkephalin thought to act on peripheral opiate receptors. The analgesic, central, cardiovascular and endocrine effects of two i.v. doses of 443C81 were investigated in 12 healthy male volunteers. Its effects were compared with those of placebo and the classical opiate dipipanone given orally using a double dummy design.443C81 produced dose-related analgesia; dipipanone 10 mg had a greater effect than the high dose 443C81. In contrast to dipipanone, 443C81 did not cause significant miosis or reduce minute volume on rebreathing CO₂ and there was no evidence of sedation. Dry mouth was reported frequently and associated with reduced salivation after all active treatments. Both 443C81 and dipipanone increased circulating prolactin and growth hormone and reduced cortisol levels. This novel enkephalin appears to possess analgesic activity and some other properties of opiates but is devoid of clinically relevant narcotic effects.