morphinans and dezocine

Sixty hospitalized subjects with chronic moderate to severe pain as a result of advanced cancer were enrolled in a randomized, parallel, double-blind trial comparing single doses and multiple doses of intramuscular dezocine (10 mg) with butorphanol (2 mg) and placebo. During the initial 6-hour efficacy evaluation, analgesia was measured using verbal and visual scriptors and vital signs, and acute toxicity information was recorded. Subjects with initial pain relief entered the 7-day multidose portion of the trial, and efficacy and toxicity data were recorded daily. After the initial dose the peak analgesia of the active agents was similar, but the duration of analgesia was longer with dezocine. After multiple doses, dezocine was superior to butorphanol in terms of length of treatment. Dezocine had less toxicity than had butorphanol after both single and repeated doses, further suggesting that dezocine may be beneficial in managing chronic cancer pain. The described study design is unique in that it compares the analgesic efficacy and toxicity of several analgesics with placebo after both single and multiple doses in the same subject. This method may prove to be an alternative pain model to evaluate chronic cancer pain.

Topics: Adult; Aged; Aged, 80 and over; Analgesics; Bridged Bicyclo Compounds, Heterocyclic; Butorphanol; Chronic Disease; Clinical Trials as Topic; Cycloparaffins; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Morphinans; Neoplasms; Pain; Random Allocation; Tetrahydronaphthalenes

The safety and efficacy of intravenous doses of dezocine (5 or 10 mg), butorphanol (1 mg), and placebo were compared in a double-blind study in 160 patients with moderate to severe postoperative pain. Analgesic efficacy was assessed for 6 hours after each dose. Mean pain relief scores were consistently higher, indicating greater pain relief, for the three active treatment groups than for the placebo group. The 10-mg dezocine dose was the most effective treatment, and 5 mg of dezocine was comparable to 1 mg of butorphanol. In the 2 hours after the first dose, 32% of the 10-mg dezocine group, 53% of the 5-mg dezocine group, 65% of the butorphanol group, and 88% of the placebo group withdrew from the study because of unsatisfactory pain relief. The differences in these percentages were statistically significant (P less than 0.05) between each active therapy group and the placebo group, and between the 10-mg dezocine group and the butorphanol group. Changes in degree of sedation were similar in the three active therapy groups. Adverse reactions were rare, mild, and equally distributed among the four treatment groups. We conclude that 10 mg of dezocine is superior to 1 mg of butorphanol, and that 5 mg of dezocine is as effective as 1 mg of butorphanol for the relief of moderate to severe postoperative pain.

Topics: Adolescent; Adult; Aged; Analgesics, Opioid; Bridged Bicyclo Compounds, Heterocyclic; Butorphanol; Clinical Trials as Topic; Cycloparaffins; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Injections, Intravenous; Male; Middle Aged; Morphinans; Pain, Postoperative; Placebos; Tetrahydronaphthalenes

The safety and efficacy of single intramuscular doses of dezocine (10 or 15 mg) were compared with butorphanol (2 mg) and placebo in 157 patients with moderate to severe postoperative pain. A verbal pain intensity scale, an analog pain intensity scale, and a verbal pain relief scale were used to record the patients' subjective assessments. The results of this study indicate that a single 10 or 15 mg intramuscular injection of dezocine is safe and more effective than placebo for four to six hours, respectively, in the treatment of moderate to severe postoperative pain (P less than .05). During the first hour of treatment the pain relief afforded by 2 mg of butorphanol was significantly greater than that afforded by 10 mg of dezocine (P less than .05), but both doses of dezocine provided long-lasting relief. The scores on all three efficacy scales were highest with the 15 mg dose of dezocine after the first hour, while the 10 mg dose of dezocine and butorphanol were compared during this period. Nausea and vomiting were the most commonly reported side effects; injection site reactions were reported more frequently in the butorphanol group.

Topics: Acute Disease; Adolescent; Adult; Bridged Bicyclo Compounds, Heterocyclic; Butorphanol; Clinical Trials as Topic; Consumer Behavior; Cycloparaffins; Double-Blind Method; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Morphinans; Nausea; Pain, Postoperative; Placebos; Tetrahydronaphthalenes; Time Factors; Vomiting

The relative performance of three analgesic rating scales--visual pain analog, verbal pain intensity, and verbal pain relief--was assessed in clinical trials with 1,497 patients and a variety of pain models. The scales correlated strongly with one another, with inconsistent and generally minimal differences in sensitivity. Overall, the verbal relief scale tended to be slightly more sensitive than the pain analog rating, which in turn showed a small advantage over the verbal pain intensity assessment. When the scores derived from the categorized ratings 1 hour after drug dosing (generally the time of peak effect) were analyzed, there was little difference whether a parametric or nonparametric approach was taken. When the cumulative measures of overall effect over 6 hours were considered, however, the nonparametric approach was decidedly more powerful. There was a similar pattern when the analog scores were analyzed. This unanticipated finding appears to be due to the cumulative measures (from all three scales) being more skewed toward the lower end of their respective ranges than are the 1-hour scores. A composite efficacy variable was defined, incorporating data from the three primary scales; this measure was found to be generally comparable in sensitivity to the individual scales and may be useful as a global summary of response. While our investigation provides evidence that any of the ratings considered will accurately reflect analgesic response, the verbal relief scale was the most sensitive and might be the best choice if a single measure is desired.

Topics: Bridged Bicyclo Compounds, Heterocyclic; Butorphanol; Clinical Trials as Topic; Cycloparaffins; Double-Blind Method; Humans; Morphinans; Morphine; Pain; Pain, Postoperative; Tetrahydronaphthalenes

Topics: Analgesics; Bridged Bicyclo Compounds, Heterocyclic; Butorphanol; Cycloparaffins; Humans; Morphinans; Pain, Postoperative; Tetrahydronaphthalenes

Nine mixed agonist-antagonist opioids were evaluated in macaque monkeys for their ability to serve as positive reinforcers and for their discriminative stimulus similarity to etorphine and ethylketazocine. For tests of reinforcing properties, various doses of each drug were substituted for codeine under a fixed-ratio 30 time-out 600 sec schedule of i.v. delivery. Discriminative properties were assessed in separate groups of monkeys for which etorphine and saline, or ethylketazocine and saline, were established as discriminative stimuli for responses maintained under a fixed-ratio 20 schedule of food delivery. Two patterns of reinforcing and discriminative stimulus properties were observed. Buprenorphine, butorphanol, GPA 1657, nalbuphine, propiram and WY 16225 (dezocine) functioned as positive reinforcers and occasioned etorphine-appropriate but not ethylketazocine-appropriate responses. dl-Profadol also functioned as a positive reinforcer; its stereoisomers occasioned etorphine-appropriate but not, in general, ethylketazocine-appropriate responses. In contrast, levallorphan and oxilorphan did not function as positive reinforcers and occasioned ethylketazocine-appropriate but no more than 30% etorphine-appropriate responses. Under these experimental conditions, the reinforcing and discriminative stimulus profiles of the mixed agonist-antagonist opioids paralleled those of etorphine-like (mu) or ethylketazocine-like (kappa) opioid agonists.

Topics: Animals; Bridged Bicyclo Compounds, Heterocyclic; Buprenorphine; Butorphanol; Cycloparaffins; Discrimination Learning; Female; Levallorphan; Macaca mulatta; Male; Morphinans; Nalbuphine; Narcotic Antagonists; Narcotics; Pyridines; Pyrrolidines; Reinforcement, Psychology; Tetrahydronaphthalenes