D-phenylalanine: a putative enkephalinase inhibitor studied in a primate acute pain model.
D-Phenylalanine, along with morphine, acetylsalicylic acid and zomepirac sodium were evaluated for their antinociceptive actions in monkeys (M. fascicularis) trained to autoregulate nociceptive stimulation using a discrete-trials, aversive-threshold paradigm. Morphine sulfate produced dose-related increases in aversive threshold which were reversible after administration of naloxone (12.5 or 25 micrograms/kg i.m.). D-Phenylalanine (500 mg/kg p.o.) produced a small increase in aversive threshold which was not statistically significant and not naloxone reversible. Acetylsalicylic acid (200 mg/kg p.o.) but not zomepirac sodium (200 mg/kg p.o.) in combination with D-phenylalanine (500 mg/kg) produced a small statistically significant increase in aversive threshold. Our results argue against the hypothesis that D-phenylalanine is responsible for increasing aversive thresholds via opiate receptor mechanisms involving increased activity of enkephalins at synaptic loci. Previous studies by others in rats and mice showed that D-phenylalanine and acetylsalicylic acid produced increases in nociceptive thresholds which were naloxone reversible. Our failure to find opiate receptor mediated analgesia in a primate model with demonstrated opiate receptor selectivity and sensitivity is discussed in terms of previous basic and clinical research indicating an analgesic role for D-phenylalanine. Possible species difference in drug action is discussed in terms of inhibition by D-phenylalanine of carboxy-peptidase-like enkephalin processing enzymes as well as inhibition of carboxypeptidase-like enkephalin degrading enzymes.
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors; D004347:Drug Interactions; D007536:Isomerism; D008252:Macaca fascicularis; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D015260:Neprilysin; D010146:Pain / Q000503:physiopathology*; D010649:Phenylalanine / Q000494:pharmacology*; D011480:Protease Inhibitors; D012684:Sensory Thresholds / Q000187:drug effects; D014046:Tolmetin / Q000031:analogs & derivatives / Q000494:pharmacology
D011480:Protease Inhibitors; D009270:Naloxone; D010649:Phenylalanine; D009020:Morphine; C020549:zomepirac; D014046:Tolmetin; D002268:Carboxypeptidases; D015260:Neprilysin; D001241:Aspirin