Selective antagonists at the opiate delta-receptor

Shaw, J.S.; Miller, Lynne; Turnbull, M J; Gormley, James J.; Morley, J. S.

doi:10.1016/0024-3205(82)90356-3

Cited by 174 publications

(71 citation statements)

References 7 publications

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“…Naloxone and ICI-l 54,129, a preferential h-antagonist (Shaw et al, 1982;Priestley et al, 1985), likewise failed to modify the withdrawal response of the paw or tail to noxious pressure. A hyperalgesic effect of naloxone has, in contrast, been reported with regard to the vocalization response to pressure or electrical stimulation in arthritic rats (Oliveras et al, 1979;Kayser and Guilbaud, 1981).…”

Section: Endogenous and Exogenous Opioid Control Of Nociception In Armentioning

confidence: 92%

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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Section: Endogenous and Exogenous Opioid Control Of Nociception In Armentioning

confidence: 92%

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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“…Another interesting finding observed in the present study is the fact that the IC50 ratio in the presence to in the absence of sodium of dynorphin- (1-1 3), which had been shown to be a strong kappa agonist (13), was less than those of mixed agonist-antagonists and significantly low when it was compared to those of other opioid agonists. This character of dynorphin- (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13) may relate to its peculiar antagonistic action (22). Inter estingly, the IC50 ratio in the presence to in the absence of sodium of ketocyclazocine, which had been reported to behave as an effective antagonist as well as a potent agonist in the guinea-pig ileum (23), was also low.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, the reduction of the potency of dynorphin-(1 13) was quite small in the presence of sodium alone, while it was large in the presence of both Gpp(NH)p and sodium (Table 4). Interestingly, the chemical structure of either U-50,488, dynorphin- (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13) or tifluadom is quite different from that of traditional benzomorphan kappa agonists such as ketocyclazocine and ethylketocyclazocine (12)(13)(14).…”

Section: Abstract-effects Of 5'-guanylylimidodiphosphate (Gpp(nh)p) Amentioning

confidence: 99%

Regulation of opioid antagonist and mu, kappa or delta agonist binding by guanine nucleotide and sodium.

Ishizuka

Oka

1984

Jpn.J.Pharmacol

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Abstract-Effectsof 5'-guanylylimidodiphosphate (Gpp(NH)p) and sodium on the inhibition by various opioids of [3H]-naloxone binding to guinea-pig brain mem brane preparations were studied.The ratio of the concentration required to produce a 50% inhibition of [3H]-naloxone binding in the presence of both Gpp(NH)p and sodium to that in the absence of both Gpp(NH)p and sodium (IC50 ratio) was less than 1 for antagonists, from 3 to 10 for mixed agonist-antagonists, from 16 to 85 for either kappa, delta, or peptide mu agonists, and more than 200 for morphine-like non peptide mu agonists.Exceptionally, the IC50 ratio of N,N-diallyl-[D-Ala2, D-Leu5] enkephalin, an opioid which had been shown not to have an agonist activity in guinea-pig ileum but to have a naloxone-reversible agonist activity in mouse vas deferens, was less than 1. The significance of the different IC50 ratio among opioids employed in the present study was discussed.

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“…In the antagonist studies, microinjections of a bis-penicillamine enkephalin analogue were alternated with the selective p-opioid receptor agonist [D-Ala2, MePhe4, Gly(ol)5] enkephalin (DAGO) (Handa et al, 1981). The opioid antagonists used in this study included naloxone and the novel 6-receptor selective compounds ICI 154,129 and ICI 174,864 (Gormley et al, 1982;Shaw et al, 1982;Cotton et al, 1984;Dray & Nunan, 1984 Unless otherwise indicated all substances were dissolved in a minimum volume of DMSO and then made up in sterile physiological saline to the required concentration. Concentrations are expressed as those ofthe salt.…”

Section: Methodsmentioning

confidence: 99%

“…In addition we have used the novel 6-opioid receptor antagonists ICI 154,129 [N,Gly-Gly-4-(CH2S)-Phe-Leu-OH] and ICI 174,864 [N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH: Aib = ax-aminoisobutyric acid] Shaw et al, 1982;Cotton et al, 1984) confirming the in vivo 6-receptor selectivity of the latter compound (Dray & Nunan, 1984). Furthermore we have observed that the endogenous opioid, P-endorphin, produced prolonged changes in the activity of central 6-opioid receptors.…”

Section: Introductionmentioning

confidence: 99%

Central δ‐opioid receptor interactions and the inhibition of reflex urinary bladder contractions in the rat

Dray

Nunan

Wire

1985

British J Pharmacology

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Selective antagonists at the opiate delta-receptor

Cited by 174 publications

References 7 publications

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

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

Regulation of opioid antagonist and mu, kappa or delta agonist binding by guanine nucleotide and sodium.

Central δ‐opioid receptor interactions and the inhibition of reflex urinary bladder contractions in the rat

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