Effects of graded oral doses of a new 5‐hydroxytryptamine/noradrenaline uptake inhibitor (Ro 15‐8081) in comparison with 60 mg codeine and placebo on experimentally induced pain and side effect profile in healthy men.

Abstract

1 Ro 15-8081 (Hoffmann-La Roche, Basle, Switzerland) is a novel mixed 5-HT/noradrenaline uptake inhibitor producing potent antinociceptive effects in animal pain models. 2 In healthy man, two models with electrically and thermally induced pain, respectively, have been shown to reliably discriminate between the effects of opioid as well as of antipyretic analgesics and placebo. 3 This study investigated the effects of single oral doses of 10, 25, and 50 mg Ro 15-8081 in comparison with 60 mg codeine and placebo on threshold and tolerance to electrically induced pain and on threshold to thermally induced pain. Furthermore, the effects on psychomotor function, self-rated subjective feelings, and side effect profile were studied. 4 Twenty healthy males participated each in five experiments in which they received, in random double-blind fashion, each of the treatments. Every experiment comprised two series of measurements before and twelve after drug administration, carried out at 30 min intervals. 5 Ro 15-8081 produced marked elevations of threshold and tolerance to electrically and of threshold to thermally induced pain. The effects of all doses of Ro 15-8081 were significantly superior to those of placebo. Threshold and tolerance to electrically induced pain were not affected differently by the three doses of Ro 15-8081, whereas the threshold to thermally induced pain was elevated significantly more by 50 mg than by 10 and 25 mg Ro 15-8081. 6 Codeine 60 mg had a more rapid onset of action and greater maximal effects than Ro 15-8081. 7 Psychomotor function, as measured by a reaction time and a fine motor control task, was not altered by any dose of Ro 15-8081, whereas 60 mg codeine produced a significant prolongation of reaction time. 8 Subjective feelings indicative of altered central nervous system arousal, well-being and mood were not influenced by Ro 15-8081. 9 Ro 15-8081 produced an only slightly higher number of side effects such as abdominal discomfort, headache, and nausea than did placebo.

Psychomotor, Respiratory and Neuroendocrinological Effects of a μ‐Opioid Receptor Agonist (Oxycodone) in Healthy Volunteers

“…Especially critical flicker fusion, Maddox wing and visual analogue scales proved sensitive to the residual effects of this opioid in accordance with previous works (Manner et al 1987a). Compared to placebo, oxycodone transiently impaired reaction time, body balance and attention, changes also described with other pagonists such as codeine (Stacher et al 1987) and dextropropoxyphene (Saarialho-Kere et al 1988b). No impairment in eye-hand coordination was noticed in the tracking test which has proved sensitive to benzodiazepines and bears relevance to real driving (Eklund 1971).…”

Abuse liability and reinforcing efficacy of oral tramadol in humans

“…The magnitude of effects was typically greatest for oxycodone, followed by the high doses of tramadol and codeine, which were comparable (see Table 1); these findings are consistent with prior studies (Jasinski et al, 1993; Epstein et al, 2006). Codeine (100 mg) produced minimal subjective effects, consistent with studies reporting on low (60–120 mg) codeine doses (Kim et al, 2002; Oyler et al, 2000; Stacher et al, 1987), while 200 mg was active and more similar to 40 mg oxycodone.…”

Subjective, psychomotor, and analgesic effects of oral codeine and morphine in healthy volunteers

“…Mild performance decrements have been found for eye-hand coordination, visual acuity (Bradley and Nicholson 1986), and one measure of driving ability (Linnoila and Hakkinen 1973) using doses ranging from 30 to 90 mg. However, oral codeine doses up to 100 mg did not impair postural balance, information processing, perception, learning and recall, reaction time, or Þne motor control (Liljequist 1981;Redpath and Pleuvry 1982;Stacher et al 1982Stacher et al , 1987Bradley and Nicholson 1986;SaarialhoKere et al 1986), and three other measures of driving ability were una¤ected or enhanced by codeine (Linnoila and Hakkinen 1973). It appears, then, that oral morphine and codeine produce mild or no psychomotor impairment and, in some cases, may actually enhance performance (Linnoila and Hakkinen 1973;Liljequist 1986;Stacher et al 1987).…”

“…However, oral codeine doses up to 100 mg did not impair postural balance, information processing, perception, learning and recall, reaction time, or Þne motor control (Liljequist 1981;Redpath and Pleuvry 1982;Stacher et al 1982Stacher et al , 1987Bradley and Nicholson 1986;SaarialhoKere et al 1986), and three other measures of driving ability were una¤ected or enhanced by codeine (Linnoila and Hakkinen 1973). It appears, then, that oral morphine and codeine produce mild or no psychomotor impairment and, in some cases, may actually enhance performance (Linnoila and Hakkinen 1973;Liljequist 1986;Stacher et al 1987). The present study sought to compare directly the e¤ects of oral morphine and codeine by studying two doses of each drug and using the same battery of psychomotor / cognitive tests so that comparisons could be made on identical dependent measures.…”