Ventilatory and Analgesic Effects of Dezocine in Humans

Gal, Thomas J.; DiFazio, Cosmo A.

doi:10.1097/00000542-198412000-00015

Cited by 34 publications

(25 citation statements)

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“…Since dezocine is a partial mu antagonist, in theory, a concerted use of dezocine together with a mu receptor agonist like morphine should decrease the analgesia effect of morphine significantly. However, it is reported that the combination of morphine and dezocine increases the analgesic effects significantly,(4) indicating that dezocine may induce analgesia through an additional mechanism(s).…”

Section: Introductionmentioning

confidence: 99%

Novel Molecular Targets of Dezocine and Their Clinical Implications

et al. 2014

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Background While dezocine is a partial mu opioid receptor agonist, it is not a controlled substance. Thus, the characterization of the molecular targets of dezocine is critical for scientific and clinical implications. The goal of this study is to characterize molecular targets for dezocine and their implications. Methods A binding screen for dezocine was performed on 44 available receptors and transporter proteins. Functional assays for the novel targets were performed along with computation calculations to locate the binding site. A G protein activation study was performed for the human kappa opioid receptor to determine whether dezocine is a kappa antagonist. Data are presented as mean ± SE. Results The affinities for dezocine were 3.7±0.7 nM for the mu receptor, 527±70 nM for the delta receptor, and 31.9±1.9 nM for the kappa receptor. Dezocine failed to induce G protein activation with kappa opioid receptor and concentration dependently inhibited kappa agonist (salvinorin A and nalbuphine) induced receptor activation, indicating that dezocine is a kappa antagonist. Two novel molecular targets (norepinephrine transporter, NET; and serotonin transporter, SERT) were identified. Dezocine concentration-dependently inhibited norepinephrine and serotonin reuptake in vitro. The half maximal inhibitory concentrations (expressed as pIC50) were 5.68±0.11 for NET and 5.86 ± 0.17 for SERT. Dezocine occupied the binding site for known NET and SERT inhibitors. Conclusions The unique molecular pharmacological profile of dezocine as a partial mu receptor agonist, a kappa receptor antagonist and a norepinephrine and serotonin reuptake inhibitor (via NET and SERT) was revealed. These discoveries reveal potentially important novel clinical implications and drug interactions of dezocine.

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Section: Introductionmentioning

confidence: 99%

Novel Molecular Targets of Dezocine and Their Clinical Implications

et al. 2014

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“…For example, several studies indicate that the doses of an opioid antagonist required to block the antinociceptive, rate-decreasing, or discriminative-stimulus effects of dezocine and d-propoxyphene are similar to the doses required to block the effects of morphine (Nickander et al 1977;Lehman and Peterson 1978). Nevertheless, other studies (Gal and DiFazio 1984) indicate that opioid antagonists are less potent in blocking these effects of dezocine and d-propoxyphene than morphine (Neil and Terenius 1981;Schaefer and Holtzman 1981;Picker et al 1993). Other reports indicate that opioid antagonists are ineffective in blocking the rate-decreasing effects of dezocine and d-propoxyphene (Leander 1979;Picker 1997).…”

Section: Introductionmentioning

confidence: 99%

Naltrexone and β-funaltrexamine antagonism of the antinociceptive and response rate-decreasing effects of morphine, dezocine, and d -propoxyphene

et al. 1999

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These data suggest that the antinociceptive effects of morphine, dezocine, and d-propoxyphene and the rate-decreasing effects of morphine and dezocine are mediated through mu opioid receptors. Overall, high doses of beta-FNA produced a greater degree of antagonism of the behavioral effects of dezocine than morphine or d-propoxyphene, confirming other reports that dezocine is a lower efficacy agonist than morphine. Additionally, the degree of antagonism produced by beta-FNA was greater for the antinociceptive effects of all three compounds than for the rate-decreasing effects.

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“…Numerous studies have demonstrated that pain and the consequent neuroendocrine stress response, which was originally considered by surgeons as homeostatic mechanisms important for 20 survival and for restitution of the patient to the preoperative status, are deleterious to the organism and are therefore considered maladaptive (4,5,10). The use of regional anesthesia during and after surgery blunts and in some instances eliminates this deleterious responses and results in a quicker ambulation, shorter convalescence and consequen tl y shorter hospi taliza tion (80,81). Related to this are a number of studies which have shown that the use of regional analgesia with local anesthetics during surgical trauma is extremely useful in delaying the onset of postoperative pain.…”

Section: Use Of Diagnostic and Therapeutic Nerve Blocksmentioning

confidence: 99%

“…This is suggested by the factthatnociceptive barrage from small 80 C fibers in deep structures produces hyperexcitability in the spinal cord that may not be the same from nociceptive input via cutaneous afferents. New pharmacologic and pharmacokinetic studies are likely to suggest the use of a combination of nonopioid and opioid that bind to different receptors to increase the analgesic efficacy and decrease (and perhaps even eliminate) side effects.…”

Section: Future Use Of Intraspinal Analgesicsmentioning

confidence: 99%