nalbuphine and dezocine

Adult patients who had arthroscopic surgery under general anesthesia and requested postoperative pain relief were randomized to receive treatment in a double-blind protocol with 5 mg of intravenous dezocine (20 patients), morphine (22 patients), nalbuphine (18 patients), or saline (24 patients). At 10-min intervals, starting with the first dose of analgesic, patients could choose up to three additional doses of the primary treatment, or choose an alternative analgesic if the primary drug was unsatisfactory. One to four doses of morphine were given as the alternate treatment if the initial treatment was dezocine or nalbuphine, and one to four doses of dezocine were given if the initial treatment was saline or morphine. The proportion of patients treated successfully by the initial treatments (i.e., not requesting alternate treatment), with P value for difference from placebo treatment, were saline 25%, nalbuphine 33% (P = 0.048), morphine 54% (P = 0.04), and dezocine 75% (P = 0.003). Dezocine and morphine are more efficacious than nalbuphine in the management of early postoperative pain. As an alternate analgesic in this study, dezocine required fewer doses to achieve patient satisfaction and was thus more efficacious than morphine. The incidence of treatment-related, adverse effects was different from that of saline or other treatments only for nalbuphine-related pain or burning on injection and dezocine-related facial itching. With respect to analgesic actions and side effects, dezocine seems more like morphine than nalbuphine.

Topics: Adult; Aged; Ambulatory Surgical Procedures; Analgesics; Bridged Bicyclo Compounds, Heterocyclic; Cycloparaffins; Female; Humans; Male; Middle Aged; Morphine; Nalbuphine; Pain; Postoperative Period; Prospective Studies; Tetrahydronaphthalenes

Myocardial ischemia (MI) could cause many complications, such as arrhythmia, ischemic cardiomyopathy, which could lead to angina and myocardial infarction. The clinical efficacy of dezocine, morphine and nalbuphine are becoming dominated in China market. This aim of this study was to investigate the effects of dezocine, morphine and nalbuphine on electrical pain threshold, temperature pain threshold and cardiac function in rats with MI.. A rat model of MI was established by ligating the coronary artery. Rats in the model group were injected with dezocine, morphine, nalbuphine and 0.9% normal saline. The effects of the three analgesics on MI rats were evaluated by comparing the electrical pain threshold, temperature pain threshold, and cardiac function index.. The electrocardiogram revealed that the model of MI was successful. The results of the electrical pain threshold and temperature pain threshold tests revealed that nalbuphine was the most sensitive after medication, followed by dezocine, and the sensitivity of morphine was the lowest. These three drugs reached its peak at two hours after administration. The analgesic effect of dezocine on electrical stimulation was the best, while nalbuphine had the best effect on temperature. The efficacy of dezocine decreased with time, while morphine basically failed at four hours after administration. The peak time of these three kinds of analgesics was selected to detect the cardiac function index in each group. Morphine had the least influence on the cardiac function index of rats, followed by nalbuphine and dezocine.. These results show that the analgesic effect of nalbuphine had the earliest and best effect with the longest duration on temperature, and had less influence and higher safety in the cardiac function test of MI rats. Hence, nalbuphine is a relatively good analgesic for MI patients. The present study provides a database for the selection of analgesics in patients with MI.

Topics: Analgesics, Opioid; Animals; Bridged Bicyclo Compounds, Heterocyclic; China; Humans; Morphine; Myocardial Ischemia; Nalbuphine; Pain Threshold; Rats; Temperature; Tetrahydronaphthalenes

Recent studies indicate that morphine is more potent as an antinociceptive agent in male than female rodents and monkeys.. To evaluate the influence of sex, nociceptive stimulus intensity and an opioid's relative efficacy on opioid-induced antinociception in rat strains (F344 and Lewis) that display differential sensitivity to morphine antinociception.. Antinociceptive testing was conducted using a rat warm-water (50-56 degrees C) tail-withdrawal procedure. Dose-response and time-course determinations were performed with various opioids.. Across the nociceptive stimulus intensities tested, the high-efficacy mu opioids morphine, etorphine, and levorphanol were equally effective in males and females, but on average 2.5-fold more potent in males. At moderate stimulus intensities, the low-efficacy mu opioid buprenorphine was approximately 0.4-fold more potent in males, and at higher stimulus intensities more potent and effective (greater maximal effect) in males. At low stimulus intensities, the low-efficacy mu opioid dezocine and the mu/kappa opioid butorphanol were greater than 8.9-fold more potent in males, and at moderate stimulus intensities were more potent and effective in males. At a low stimulus intensity, the mu/kappa opioid nalbuphine was more potent and effective in males. At stimulus intensities in which buprenorphine, dezocine, butorphanol, and nalbuphine produced maximal effects in males but not females, these opioids antagonized the effects of morphine in females. Genotype-related differences were noted as opioids were generally more potent in F344 than Lewis males, whereas no consistent differences were observed between F344 and Lewis females.. That sex differences in the potency and effectiveness of opioids increased with decreases in the opioid's relative efficacy and with increases in the nociceptive stimulus intensity suggests that the relative efficacy of mu opioids as antinociceptive agents is greater in male than female rats.

Topics: Analgesics, Opioid; Animals; Bridged Bicyclo Compounds, Heterocyclic; Buprenorphine; Butorphanol; Cycloparaffins; Dose-Response Relationship, Drug; Etorphine; Female; Genotype; Levorphanol; Male; Morphine; Nalbuphine; Rats; Rats, Inbred F344; Rats, Inbred Lew; Reaction Time; Receptors, Opioid, mu; Sex Factors; Species Specificity; Tetrahydronaphthalenes

We examined the effects of several opioids that vary in intrinsic efficacy at the mu-opioid receptor alone and in combination with morphine in a rat warm water tail withdrawal procedure using 50 degrees C and 52 degrees C water (i.e., low- and high-stimulus intensities). Morphine, levorphanol, dezocine, and buprenorphine produced dose-dependent increases in antinociception using both stimulus intensities. Butorphanol produced maximal levels of antinociception at the low, but not at the high, stimulus intensity, whereas nalbuphine failed to produce antinociception at either stimulus intensity. For cases in which butorphanol and nalbuphine failed to produce antinociception alone, these opioids dose-dependently antagonized the effects of morphine. When levorphanol, dezocine, and buprenorphine were combined with morphine, there was a dose-dependent enhancement of morphine's effects. Similar effects were obtained at the low-stimulus intensity when butorphanol was administered with morphine. In most cases, the effects of these combinations could be predicted by summating the effects of the drugs when administered alone. These results indicate that the level of antinociception produced by an opioid is dependent on the intrinsic efficacy of the drug and the stimulus intensity. Furthermore, the level of antinociception produced by the opioid, not necessarily the opioids' intrinsic efficacy, determines the type of interaction among opioids.. Compared with high-efficacy opioids, lower efficacy opioids produce lower levels of pain relief, especially in situations of moderate to severe pain. When opioids are given in combination, the effects can only be predicted on the basis of the antinociception obtained when the drugs are administered alone.

Topics: Analgesics, Opioid; Animals; Bridged Bicyclo Compounds, Heterocyclic; Buprenorphine; Butorphanol; Cycloparaffins; Dose-Response Relationship, Drug; Drug Combinations; Levorphanol; Morphine; Nalbuphine; Narcotics; Nociceptors; Pain; Physical Stimulation; Rats; Rats, Long-Evans; Receptors, Opioid, mu; Tetrahydronaphthalenes

The ability of morphine, fentanyl, butorphanol, nalbuphine, and dezocine to compete with radiolabeled ligands for binding at the mu1, mu2, kappa1, and delta opioid receptors and the sigma receptor was characterized. In the absence of sodium, the potency of opioid receptor competition at each receptor site was found to be: mu1-fentanyl > butorphanol > morphine > or = dezocine = nalbuphine; mu2-butorphanol > fentanyl > nalbuphine > morphine = dezocine; kappa1-butorphanol > nalbuphine >> morphine > or = dezocine > fentanyl; and delta-butorphanol > nalbuphine > or = dezocine > morphine > fentanyl. For all five compounds, competition at the sigma receptor was weak, with nalbuphine and dezocine having Kis of approximately 0.5 microM and the other opioids having Kis of greater than 1 microM. Since the presence of 100 mM NaCl during the competitive binding decreased the K(i), to varying degrees, of all five opioids at the mu1 and delta receptors and of some of the opioids at the mu2 and kappa1 receptors, the five compounds studied appear to differ in efficacy at the five receptor sites.

Topics: Analgesics, Opioid; Analysis of Variance; Animals; Binding, Competitive; Bridged Bicyclo Compounds, Heterocyclic; Butorphanol; Cycloparaffins; Fentanyl; Guinea Pigs; In Vitro Techniques; Male; Morphine; Nalbuphine; Narcotic Antagonists; Rats; Rats, Sprague-Dawley; Receptors, Opioid; Tetrahydronaphthalenes

Responding in patas monkeys was maintained under a multiple schedule of food presentation. One component of the multiple schedule was a repeated-acquisition task in which the discriminative stimuli for left- and right-key responses changed each session (learning). In the other component, the discriminative stimuli were the same each session (performance). The mixed agonist-antagonists dezocine, GPA 1657 and nalbuphine each produced dose-related decreases in the overall rate of responding in each component of the multiple schedule. In general each drug produced greater rate-decreasing effects in the learning than in the performance component, although this differential effect between components was less apparent with dezocine. In the learning component low doses of nalbuphine and GPA 1657 produced small increases in percentage of errors but had little or no effect on response rate. A similar effect was obtained with dezocine in only one of four subjects tested. At doses which produced comparable rate-decreasing effects dezocine also exerted the least disruptive effect on the within-session pattern of acquisition. High doses of each drug disrupted accuracy in each component of the multiple schedule. In contrast to the other drugs tested, buprenorphine had virtually no effect on response rate or percentage of errors in either component of the multiple schedule across a wide range of doses (0.01-3.2 mg/kg). The results suggest that, among the mixed agonist-antagonist, buprenorphine is unique in that it does not disrupt the acquisition or performance of complex discrimination in patas monkeys.

Topics: Animals; Benzomorphans; Bridged Bicyclo Compounds, Heterocyclic; Buprenorphine; Conditioning, Operant; Cycloparaffins; Discrimination Learning; Erythrocebus patas; Female; Male; Nalbuphine; Narcotic Antagonists; Narcotics; Reinforcement, Psychology; 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

Dezocine in equianalgesic intravenous doses depressed respiratory response to CO2 breathing of six healthy subjects to approximately the same degree as morphine but with a more rapid onset and higher peak depression. The depression was dose related up to 30 mg/70 kg but was not increased by an additional 10 mg/70 kg dose. Its duration of effect was approximately the same as that of morphine. Respiratory depression by dezocine was promptly and almost completely antagonized by 0.4 mg naloxone, but antagonism lasted less than 1 hr. Healthy subjects found dezocine less pleasant than morphine and after large doses reported sensations suggestive of psychotomimetic effects. A ceiling effect for respiratory depression has now been demonstrated for three agonist-antagonist analgesics: nalorphine, nalbuphine, and dezocine. It is not yet clear to what extent this is a general characteristic of agonist-antagonist analgesics.

Topics: Adult; Bridged Bicyclo Compounds, Heterocyclic; Carbon Dioxide; Cycloparaffins; Dose-Response Relationship, Drug; Humans; Injections, Intravenous; Male; Morphine; Nalbuphine; Naloxone; Respiration Disorders; Tetrahydronaphthalenes