Morphine-induced straub tail response: Mediated by central μ2-opioid receptor

Nath, Chandishwar; Gupta, M. K. Das; Patnaik, G. K.; Dhawan, K.N.

doi:10.1016/0014-2999(94)90543-6

Cited by 34 publications

(23 citation statements)

References 6 publications

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“…In the case of F, C and T, they are most probably of the m type. This is consistent with previous reports that m opioid receptors are involved in the mechanisms of opioid induced antinociception, Straub tail, muscle rigidity, catalepsy and other morphine-like behavioural effects in rats (Negri et al, 1992;Nath et al, 1994;Chen et al, 1996;Piepponen et al, 1997).…”

Section: Discussionsupporting

confidence: 93%

Neurotoxicity evaluation of fentanyl analogs in rats

Vučković¹,

Vujovic-Savic²,

Ivanović³

et al. 2012

ACTA VET-BEOGRAD

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This study aimed at evaluating the neurotoxicity of fentanyl analogs: (±)-cis-3-carbomethoxy fentanyl (C) and (±)-trans-3-carbomethoxy fentanyl (T) in rats. C and T are less potent (2.4-3.1 and 8.4-12.3 times, respectively) than fentanyl (F) in producing both antinociception and morphine-like neurotoxic effects: loss of pinna reflex, Straub tail, impairment of motor coordination, catalepsy, loss of corneal reflex and loss of righting reflex. All of the effects tested were dose-dependent and they were abolished by pretreatment with naloxone, nonselective antagonist of opioid receptors, indicating that they are mediated via opioid receptors. Further, F, C and T exhibited similar relative potencies in producing all tested effects, indicating that similar receptors are involved in producing antinociceptive and neurotoxic effects, most probably of μ type. By using equiantinociceptive doses, C and T produced significantly shorter duration of both antinociception and neurotoxicity than F. No significant differences between therapeutic indices for F, C and T were found, indicating that these compounds are equally safe and tolerable in respect to the neurotoxic effects tested. Neurotoxicity testing presented in this paper may be useful in studying the structure-activity relationship of opioid congeners

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Section: Discussionsupporting

confidence: 93%

Neurotoxicity evaluation of fentanyl analogs in rats

Vučković¹,

Vujovic-Savic²,

Ivanović³

et al. 2012

ACTA VET-BEOGRAD

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“…The mdr1a(Ϫ/Ϫ) mice administered norbuprenorphine exhibited Straub tails, the tail held erect because of opioid-induced contraction of the sacrococcygenus muscle (Bilbey et al, 1960;Aceto et al, 1969). This has been shown to be mediated through the central 2 opioid receptor subtype (Nath et al, 1994). The mdr1a(Ϫ/Ϫ) mice also exhibited loss of righting reflex, another 2 opioid receptormediated effect (Oka et al, 1992;Kamei et al, 1996).…”

Section: Role Of P-gp In Brain Exposure Of Norbuprenorphine 57mentioning

confidence: 99%

P-Glycoprotein Is a Major Determinant of Norbuprenorphine Brain Exposure and Antinociception

Brown

Campbell

Crafford

et al. 2012

J Pharmacol Exp Ther

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Norbuprenorphine is a major metabolite of buprenorphine and potent agonist of , ␦, and opioid receptors. Compared with buprenorphine, norbuprenorphine causes minimal antinociception but greater respiratory depression. It is unknown whether the limited antinociception is caused by low efficacy or limited brain exposure. Norbuprenorphine is an in vitro substrate of the efflux transporter P-glycoprotein (Mdr1), but the role of P-glycoprotein in norbuprenorphine transport in vivo is unknown. This investigation tested the hypothesis that limited norbuprenorphine antinociception results from P-glycoprotein-mediated efflux and limited brain access. Human P-glycoprotein-mediated transport in vitro of buprenorphine, norbuprenorphine, and their respective glucuronide conjugates was assessed by using transfected cells. P-glycoprotein-mediated norbuprenorphine transport and consequences in vivo were assessed by using mdr1a(ϩ/ϩ) and mdr1a(Ϫ/Ϫ) mice. Antinociception was determined by hotwater tail-flick assay, and respiratory effects were determined by unrestrained whole-body plethysmography. Brain and plasma norbuprenorphine and norbuprenorphine-3-glucuronide were quantified by mass spectrometry. In vitro, the net P-glycoproteinmediated efflux ratio for norbuprenorphine was nine, indicating significant efflux. In contrast, the efflux ratio for buprenorphine and the two glucuronide conjugates was unity, indicating absent transport. The norbuprenorphine brain/plasma concentration ratio was significantly greater in mdr1a(Ϫ/Ϫ) than mdr1a(ϩ/ϩ) mice. The magnitude and duration of norbuprenorphine antinociception were significantly increased in mdr1a(Ϫ/Ϫ) compared with mdr1a(ϩ/ϩ) mice, whereas the reduction in respiratory rate was similar. Results show that norbuprenorphine is an in vitro and in vivo substrate of P-glycoprotein. P-glycoprotein-mediated efflux influences brain access and antinociceptive, but not the respiratory, effects of norbuprenorphine.

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“…Previous studies have shown that implantation of two morphine pellets (75 mg, free base) results in a steady state of plasma morphine levels by 3 days post-pellet implant, ranging between 86.8±13.1 and 156±45 ng/ml, that was maintained through 12 days post-pellet implant (Gold et al, 1994;Yoburn et al, 1985). Mice were visually evaluated for signs of morphine-induced agonist actions by assessing the presence or absence of the Straub tail response and by observing the characteristic stereotypic locomotor actions in the home cage (Hasegawa et al, 1990;Nath et al, 1994). No signs of withdrawal (i.e.…”

Section: Sustained Morphine Administrationmentioning

confidence: 99%

“…All mice that received morphine pellets demonstrated clear Straub tail behavior and exhibited characteristic cagecircling behavior within 30 min of morphine pellet implantation; these effects are typical of morphine agonist actions (Hasegawa et al, 1990;Nath et al, 1994). Paw-withdrawal latencies were determined in mice prior to implantation of morphine or placebo pellets and again 6 days following pellet implant.…”

Section: Nk-1 Receptor Antagonist In Micementioning

confidence: 99%

Role of NK-1 neurotransmission in opioid-induced hyperalgesia

King

Gardell

Wang

et al. 2005

Pain

153

128

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Opiates are among the most important drugs for treatment of moderate to severe pain and prolonged opiate administration is often required to treat chronic pain states. We investigated the neurobiological actions of sustained opiate administration revealing paradoxical pronociceptive adaptations associated with NK-1 receptor function. Sustained morphine delivered over 6 days elicited hyperalgesia in rats and mice during the period of opiate delivery. Sustained morphine administration increased substance P (SP) and NK-1 receptor expression in the spinal dorsal horn. Sustained morphine treatment also enhanced capsaicin-evoked SP release in vitro, and increased internalization of NK-1 receptors in response to noxious stimulation. While NK-1 receptor internalization was observed primarily in the superficial laminae of placebo-treated rats, NK-1 receptor internalization was seen in both superficial and deep lamina of the dorsal horn in morphinetreated animals. Morphine-induced hyperalgesia was reversed by spinal administration of an NK-1 receptor antagonist in rats and mice, and was observed in wildtype (NK-1 +/+ ), but not NK-1 receptor knockout (NK-1 −/− ), mice. These data support a critical role for the NK-1 receptor in the expression of sustained morphine-induced hyperalgesia. Additionally, these data indicate that sustained opiate administration induces changes reminiscent of those associated with inflammatory pain. These opiate-induced changes might produce unintended deleterious actions in the course of pain treatment in patients. Understanding of sustained morphine-induced neurochemical changes will help identify approaches that limit the deleterious actions of opiates.

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Morphine-induced straub tail response: Mediated by central μ2-opioid receptor

Cited by 34 publications

References 6 publications

Neurotoxicity evaluation of fentanyl analogs in rats

Neurotoxicity evaluation of fentanyl analogs in rats

P-Glycoprotein Is a Major Determinant of Norbuprenorphine Brain Exposure and Antinociception

Role of NK-1 neurotransmission in opioid-induced hyperalgesia

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