Human tolerability studies with D-Met2,Pro5-enkephalinamide

As reported previously D-Met2,Pro5-enkephalinamide (EA) is a highly active enkephalin analogue. To examine its human tolerability male volunteers were treated s.c. with increasing doses (0.1-30.0 mg). The observed autonomic effects were as follows: feeling of heaviness in the limbs, dry mouth, pallor of the face and conjunctival injection. There was no significant change in blood pressure, pulse and respiratory frequency. The autonomic effects appeared within 15-30 min. However, its effects on mood and wakefulness i.e. slight drowsiness, decrease in psychic tension and emotional detachment developed only later. The serum prolactin level increased dose-dependently, while the growth hormone (HGH) content showed biphasic dose-response pattern. The TSH content increased only at the highest doses applied (10.0-30.0 mg).