UI - 000225

AU - Halpern LM

AU - Dong WK

TI - D-phenylalanine: a putative enkephalinase inhibitor studied in a primate acute pain model

AB - 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 UI - 86176317

SO - Pain 1986;24:223-237