Toward the development of a potent, nonsedating, oral analgesic

The separate and combined analgesic effects of 10 mg of oral amphetamine sulfate and 25 mg of oral anileridine dihydrochloride were studied in 24 healthy, adult, male volunteers. Tolerance of progressively increasing pain produced by the Submaximum Effort Tourniquet Technique was tested four times in each subject: after amphetamine, after anileridine, after the combination, and after a matching placebo. Treatments were administered double blind and in counterbalanced order. Elapsed time to report of slight, moderately distressing, very distressing, and unbearable pain was recorded on each trial. The four oral treatments differed significantly for very distressing and for unbearable pain. At each of the three upper pain levels, the mean tolerance times for anileridine and amphetamine were similar; each was longer than placebo but shorter than the combination; and the effect of the combination was approximately the sum of the effects of the two components.