Comparative action of Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 analogs on intestinal motility and nociception in rats.

Central (i.c.v.) effects of D-Tyr-D-Leu-[N-Me]-Phe-Gln-Pro-Gln-Arg-Phe-NH2 [(1DME)Y8Fa] and D-Tyr-D-Leu-D-Phe-Gln-Pro-Gln-Arg-Phe-NH2 [(3D)Y8Fa], synthetic analogs of Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 on intestinal myoelectric activity and nociception were studied and compared to that of D-Ala2-Met5-enkephalinamide in rats. The duration of disruption of intestinal migrating myoelectric complexes, induced by p.o. administration of a test meal was significantly shortened (P < .01) by (1DME)Y8Fa and (3D)Y8Fa (8, 40 and 80 micrograms/kg) and D-Ala2-Met5-enkephalinamide (40 and 80 micrograms/kg). The coadministration of any two of these drugs, at doses of nonmeasurable effect when given alone (2 micrograms/kg), has also reduced the duration (P < .01) of the postprandial intestinal motor profile. Both separate and combined effects of drugs were antagonized by naloxone (1 mg/kg s.c.). In contrast, in the tail-flick test, analgesia induced by D-Ala2-Met5-enkephalinamide (40 micrograms/kg i.c.v.) was blocked by (1DME)Y8Fa, (3D)Y8Fa (8 micrograms/kg) and naloxone (1 mg/kg s.c.). The coadministration of (1DME)Y8Fa and (3D)Y8Fa at doses of no proper effect when given alone (8 micrograms/kg) has significantly (P < .01) reduced the latency time. This effect was not blocked by naloxone (1 mg/kg s.c.). It is concluded that the Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 analogs, (1DME)Y8Fa and (3D)Y8Fa, when given i.c.v. exert effects similar to opiate agonists and antagonists on intestinal myoelectrical activity and on nociception, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)