The binding spectrum of narcotic analgesic drugs with different agonist and antagonist properties

Magnan, Jacques; Paterson, S.J.; Tavani, Alessandra; Kosterlitz, H. W.

doi:10.1007/bf00495865

Cited by 509 publications

(160 citation statements)

References 29 publications

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“…NAT is a specific, non-selective opioid receptor antagonist but has longer duration of action than naloxone, another commonly used opioid receptor antagonist [28]. To investigate whether opioid receptors participate in the induction of METH-induced behavioral sensitization, mice were injected i.p.…”

Section: Effects Of Nat On the Induction Of Behavioral Sensitizationmentioning

confidence: 99%

Attenuation of methamphetamine-induced behavioral sensitization in mice by systemic administration of naltrexone

Chiu

2005

Brain Research Bulletin

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Repeated intermittent exposure to psychostimulants was found to produce behavioral sensitization. The present study was designed to establish a mouse model and by which to investigate whether opioidergic system plays a role in methamphetamine-induced behavioral sensitization. Mice injected with 2.5 mg/kg of methamphetamine once a day for 7 consecutive days showed behavioral sensitization after challenge with 0.3125 mg/kg of the drug on day 11, whereas mice injected with a lower daily dose (1.25 mg/kg) did not. Mice received daily injections with either 1.25 or 2.5 mg/kg of methamphetamine showed behavioral sensitization after challenge with 1.25 mg/kg of the drug on days 11, 21, and 28. To investigate the role of opioidergic system in the induction and expression of behavioral sensitization, long-acting but non-selective opioid antagonist naltrexone was administrated prior to the daily injections of and challenge with methamphetamine, respectively. Our results show that the expressions of behavioral sensitization were attenuated by pretreatment with 10 or 20 mg/kg of naltrexone either during the induction period or before methamphetamine challenge when they were tested on days 11 and 21. These results indicate that repeated injection with methamphetamine dose-dependently induced behavioral sensitization in mice, and suggest the involvement of opioid receptors in the induction and expression of methamphetamine-induced behavioral sensitization.

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Section: Effects Of Nat On the Induction Of Behavioral Sensitizationmentioning

confidence: 99%

Attenuation of methamphetamine-induced behavioral sensitization in mice by systemic administration of naltrexone

Chiu

2005

Brain Research Bulletin

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“…Fentanyl was chosen as the p-agonist; for its receptor selectivity in binding tests see Magnan et al (1982). U-50,488H (trans-3,4- Leander, 1983;Vonvoigtlander et al, 1983;Burkard, 1984;Hayes et al, 1985;.…”

Section: Drugs Drug Administration and Analysismentioning

confidence: 99%

Spinal antinociceptive actions of μ‐ and κ‐opioids: the importance of stimulus intensity in determining ‘selectivity’ between reflexes to different modalities of noxious stimulus

Parsons

Headley

1989

British J Pharmacology

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1In electrophysiological experiments in spinalized rats, y-and K-opioids were tested intravenously on the responses of single motoneurones to electronically controlled, alternating noxious heat and noxious pinch stimuli. The effects of u-and K-opioids were compared with those of the general anaesthetic x-chloralose and the dissociative anaesthetic/PCP ligand ketamine. 2 The K-opioids U-50,488 (0.5-16 mg kg'-i.v.) and tifluadom (0.05-1.6 mg kg-1 i.v.) had very similar actions to the p-opioid fentanyl (0.5-16 pg kg '-i.v.). Thus all three agonists reduced thermal and mechanical nociceptive reflexes in parallel and in a dose-dependent manner, but only so long as neuronal responses to the alternating stimuli elicited similar excitability levels in the neurone under study. Ketamine (0.5-16mgkg-1 i.v.) had similar actions to the opioids whereas a-chloralose (20 mg kg -i.v.) had very little effect on neuronal responsiveness. 3 Apparently 'selective' depressions by both p-and K-opioids could be orchestrated by a deliberate mismatch of the intensities of alternating noxious heat and pinch stimuli; as measured by neuronal firing rate, the weaker of the responses to either type of stimulus was invariably reduced to a greater degree. 4 Similar 'selectivity' could be demonstrated for both p-and K-ligands when the weaker and stronger responses were of the same modality, being applied by the same pincher device but with alternating applied force. 5 It is concluded that the 'selective' spinal actions of K-opioids seen in non-thermal over thermal behavioural models of nociception is likely to be related to the relative intensities, rather than the modalities, of the noxious stimuli used. The validity of the interpretation of results obtained in such behavioural studies is discussed.

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“…As is explained elsewhere (Millan, 1986), this paradoxical analgesia appears to be due to a peripheral action of naloxone upon extra-CNS opioid receptors with poorly defined characteristics, probably located within the paw itself. MR 2266, which possesses a much greater ability to block K-receptors than does naloxone (Magnan et al, 1982;Vonvoigtlander et al, 1983), decreased thresholds for withdrawal of the paw to noxious pressure; that is, it potentiated the hyperalgesia. This was a highly specific and selective action, in that (1) kg 2266 did not affect the response to noxious heat, (3) MR 2266 was inactive in control rats, and (4) MR 2266 proved inactive in rats with acute inflammation.…”

Section: Endogenous and Exogenous Opioid Control Of Nociception In Armentioning

confidence: 99%

A model of chronic pain in the rat: functional correlates of alterations in the activity of opioid systems

Millan¹,

Członkowski²,

Pilcher³

et al. 1987

J. Neurosci.

111

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Intradermal inoculation of rats at the tail base with Mycobacterium butyricum led to the gradual development of an arthritic swelling of the limbs which peaked at 3 weeks and subsided thereafter. Arthritic rats displayed a loss of body weight, hypophagia, and hypodipsia in addition to a disruption of the diurnal rhythms of ingestive behavior and of core temperature. The activity of adenohypophyseal beta- endorphin-(beta-EP) secreting corticotrophs, in contrast to prolactin- (PRL) secreting lactotrophs, was increased in arthritic rats. Indeed, hypertrophy of the adrenal glands was seen. Arthritic rats also showed an elevation in spinal cord levels of immunoreactive dynorphin (DYN), an endogenous ligand of the kappa-opioid receptor. The paws and tail of arthritic rats showed lower thresholds in response to noxious pressure (hyperalgesia), higher thresholds in response to noxious heat (hypoalgesia), and no change in their response to noxious electrical stimulation. Neither naloxone nor ICI-154, 129 (a preferential delta- receptor antagonist) modified the responses of the paw or tail to pressure. However, MR 2266 (an antagonist with higher activity at kappa- receptors) decreased thresholds to pressure in arthritic, but not control, rats; that is, it potentiated the hyperalgesia. This action was stereospecific. None of the antagonists modified the response to heat. MR 2266 did not affect the response to pressure in rats with acute inflammation produced by yeast. Thus, the potentiation of pressure hyperalgesia by MR 2266 in chronic arthritic rats is highly selective. Arthritic rats showed a reduced response to the analgesic effect of a kappa-agonist (U-50,488H), whereas the response to a mu- agonist (morphine) was enhanced. These effects were specific to nociception in that their influence upon endocrine secretion (PRL and beta-EP) was otherwise changed. The secretion of beta-EP and PRL was stimulated by both morphine and U-50,488H, and the influence of U- 50,488H upon the release of beta-EP (from the adenohypophysis) was enhanced in arthritic rats. It is suggested that polyarthritis is a complex condition entailing many changes, both behavioral and endocrinological. Further, arthritic rats cannot simply be described as “hyperalgesic”: of critical importance is the nature of the nociceptive stimulus applied. The parallel alterations in spinal cord pools of DYN and kappa-receptors (see also Millan et al., 1986) and the changes in the influence on nociception of kappa-agonists and kappa-antagonists suggest an increased activity of spinal DYN. Thus, spinal kappa- receptors may play a role in the modulation of nociception under chronic pain.(ABSTRACT TRUNCATED AT 400 WORDS)

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The binding spectrum of narcotic analgesic drugs with different agonist and antagonist properties

Cited by 509 publications

References 29 publications

Attenuation of methamphetamine-induced behavioral sensitization in mice by systemic administration of naltrexone

Attenuation of methamphetamine-induced behavioral sensitization in mice by systemic administration of naltrexone

Spinal antinociceptive actions of μ‐ and κ‐opioids: the importance of stimulus intensity in determining ‘selectivity’ between reflexes to different modalities of noxious stimulus

A model of chronic pain in the rat: functional correlates of alterations in the activity of opioid systems

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