Opiate-like peptides. Part XIII. Synthesis and analgesic activity of met-enkephalin analogs substituted in position 4 with D-4-halogenophenylalanine.

Six met-enkephalin derivatives substituted in position 4 with D-4-chlorophenylalanine or D-4-fluorophenylalanine were obtained. Their antinociceptive activity was determined after icv administration to rats by tail immersion test. Cataleptic activity and the influence of the analogs obtained on the body temperature were also estimated. All compounds exerted analgesic activity, which was decreased significantly by naloxone. Almost all compounds appeared cataleptic, some of them caused hypothermia.