Pharmacological profile of PD 117302, a selective κ‐opioid agonist

Leighton, G.E.; Johnson, Megan A.; Meecham, Ken; Hill, R.G.; Hughes, J.

doi:10.1111/j.1476-5381.1987.tb11398.x

Cited by 89 publications

(36 citation statements)

References 17 publications

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“…Recently, ic-agonists have received particular attention owing to their potentially analgesic properties. Indeed, systemic administration of non-peptide opioid receptor agonists, such as PD-1 17302, induce antinociception (Leighton et al, 1987). We showed that this K-agonist, like morphine, was effective in inhibiting plasma extravasation induced by electrical nerve stimulation, but not that induced by exogenous SP ( Table 1), suggesting that x-agonists act through receptors located presynaptically on afferent fibres to inhibit tachykinin release.…”

Section: Discussionmentioning

confidence: 84%

A non‐peptide NK₁‐receptor antagonist, RP 67580, inhibits neurogenic inflammation postsynaptically

Moussaoui

Montier

Carruette

et al. 1993

British J Pharmacology

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1 The non-peptide neurokinin NKI-receptor antagonist, RP 67580 (3aR, 7aR), a perhydroisoindolone derivative, powerfully reduced plasma extravasation in rat hind paw skin induced by local application of xylene (ID50 = 0.03 mg kg ', i.v.) or capsaicin (ID50 = 0.06 mg kg-', i.v.), or by i.v. injection of exogenous substance P (SP) or septide ([pGlu6,) (IDm = 0.04-0.05 mg kg ', i.v.). RP 67580 (1 mg kg-', i.v.) also abolished capsaicin-induced nasal fluid hypersecretion (by 82 ± 5%). These effects were found to be stereospecific, the enantiomer, RP 68651 (3aS, 7aS), being inactive at lmgkg-', i.v. 2 In rats neonatally treated with capsaicin (50 mg kg-', s.c.), plasma extravasation induced by SP was significantly increased (by 43 ± 7%). RP 67580 (1 mg kg-', i.v.) completely inhibited the SP-induced plasma extravasation in capsaicin neonatally treated-animals, as it did in control animals. This result suggests that RP 67580 acts at the postsynaptic level for the inhibition of plasma extravasation.3 Opioid receptor agonists, ft-(morphine) and ic-(PD-117302) at 10mgkg-', s.c., in contrast to NKI-receptor antagonists, did not inhibit plasma extravasation induced by exogenous SP. They were, however, partially effective against plasma extravasation induced by electrical nerve stimulation (74 ± 4% and 48 ± 9% inhibition at 10 mg kg', s.c. of morphine and PD-1 17302, respectively, compared to 90 ± 3% inhibition obtained with RP 67580, 3 mg kg-', s.c.). These results indicate the presynaptic action of opioid receptor agonists, in contrast to the postsynaptic action of NK,-receptor antagonists for the inhibition of plasma extravasation. 4 Ligature of the saphenous nerve distal to the point of electrical stimulation, local application of lignocaine to the saphenous nerve, neonatal capsaicin pretreatment, and colchicine at very low doses (120 jig kg' day-' given for 3 days) were found to prevent plasma extravasation elicited by electrical nerve stimulation. 5 The foregoing results demonstrate that the non-peptide NK,-receptor antagonist, RP67580, is a potent inhibitor of plasma extravasation induced in skin by NK,-receptor agonists, by local application of chemical irritants (capsaicin or xylene) or by electrical nerve stimulation. Moreover, opioid receptor agonists and colchicine inhibit plasma extravasation induced by electrical nerve stimulation but not that elicited by exogenous SP. Therefore, it is possible to inhibit neurogenic inflammation either at the presynaptic level with opioid receptor agonists and colchicine, or at the postsynaptic level with NK,-receptor antagonists, and that the new non-peptide NK,-receptor antagonists may have a great potential for alleviation of inflammation in various pathological syndromes in man.

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Section: Discussionmentioning

confidence: 84%

A non‐peptide NK₁‐receptor antagonist, RP 67580, inhibits neurogenic inflammation postsynaptically

Moussaoui

Montier

Carruette

et al. 1993

British J Pharmacology

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“…In an attempt to determine whether K-agonists exert their antinociceptive effect at a spinal or a supraspinal site we have evaluated three selective Kopioids, PD117302 (Clark et al, 1988;Leighton et al, 1987), U50488 (VonVoigtlander et al, 1983) and U69593 (Lahti et al, 1985) for their effects against mechanical and thermal noxious stimuli following intravenous, intracerebroventricular or intrathecal administration of drugs. Because of the rapid degradation of dynorphin that occurs in vivo and the nonopioid effect of flaccid paralysis that has been reported following intrathecal injection of this peptide, it was decided not to include it in this study.…”

Section: Introductionmentioning

confidence: 99%

κ‐Opioid agonists produce antinociception after i.v. and i.c.v. but not intrathecal administration in the rat

Leighton

Rodrı́guez

Hill

et al. 1988

British J Pharmacology

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1 Nociceptive thresholds to noxious mechanical (paw pressure) and thermal (tail flick) stimuli were recorded in conscious rats. The effects of three selective K-opioid receptor agonists on the responses to these stimuli were determined following intravenous, intracerebroventricular or intrathecal administration. Results were compared with those obtained with morphine. 2 Following intravenous administration PD1 17302, U50488, U69593 and morphine produced steep parallel dose-response curves indicating antinociceptive activity when evaluated in the paw pressure test. When U50488 and U69593 were tested at a single dose of 3.3 mgkg' no effect was seen in the tail flick test. 3 When given by the intrathecal route only morphine was effective at increasing the nociceptive threshold. PD1 17302, U50488 and U69593 were without effect in either the paw pressure or tail flick tests when tested at doses up to 100lpg per rat. PD117302 caused flaccid paralysis of the hindlimbs following intrathecal administration at the top dose tested. This effect was not reversible by naloxone. 4 All three K-Opioid receptor agonists produced naloxone-reversible antinociception in the paw pressure test, and to a lesser extent in the tail flick test, when injected directly into the third cerebral ventricle with the maximum effect occurring between 5 and 10 min after administration and declining back to control levels by 60min. Morphine had a much slower onset of action with the peak effect being observed 30 min after dosing. 5 It is concluded that, under our experimental conditions in the rat, the antinociceptive effects of K-agonists are likely to be operated via an action at a supraspinal rather than a spinal site.

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“…They were gently placed on a hot plate thermostatically maintained at 55˚C [13]. The time in sec at which the animals displayed nociceptive responses exhibited as licking of the front paws or fanning (blowing) the hind paws was recorded and the animals were removed from the plate.…”

Section: Screening For Analgesic Activity-hot Plate Methodsmentioning

confidence: 99%

“…The effect of the different extracts of A. Lebbeck on pain sensation was tested using hot plate method [13]. Administration of the different extracts at doses of 1 g/kg I.p, except n-butanol extract which was administered in dose of 0.25 g/kg, induced variable increases in the pain threshold in the hot plate test.…”

Section: Analgesic Activitymentioning

confidence: 99%

Evaluation of Some Biological Activities of <i>Albizia lebbeck</i> Flowers

Farag¹,

Gamal²,

Kalil³

et al. 2013

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Reviewing the current literature for the importance of the plant Albizia lebbeck L. growing worldwide revealed many biological interests. However, the species growing in Saudi Arabia has not received due attention. The present study was undertaken to study antipyretic, analgesic, estrogenic and anti-inflammatory activities of five different fractions from successive extraction of Albizia lebbeck flowers: n hexane, dichloromethane, ethyl acetate, n-butanol as well as the 70% total alcohol. The flowers showed reasonable antipyretic, analgesic, estrogenic and anti-inflammatory activities.

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Pharmacological profile of PD 117302, a selective κ‐opioid agonist

Cited by 89 publications

References 17 publications

A non‐peptide NK₁‐receptor antagonist, RP 67580, inhibits neurogenic inflammation postsynaptically

A non‐peptide NK₁‐receptor antagonist, RP 67580, inhibits neurogenic inflammation postsynaptically

κ‐Opioid agonists produce antinociception after i.v. and i.c.v. but not intrathecal administration in the rat

Evaluation of Some Biological Activities of <i>Albizia lebbeck</i> Flowers

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Pharmacological profile of PD 117302, a selective κ‐opioid agonist

Cited by 89 publications

References 17 publications

A non‐peptide NK1‐receptor antagonist, RP 67580, inhibits neurogenic inflammation postsynaptically

A non‐peptide NK1‐receptor antagonist, RP 67580, inhibits neurogenic inflammation postsynaptically

κ‐Opioid agonists produce antinociception after i.v. and i.c.v. but not intrathecal administration in the rat

Evaluation of Some Biological Activities of &lt;i&gt;Albizia lebbeck&lt;/i&gt; Flowers

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A non‐peptide NK₁‐receptor antagonist, RP 67580, inhibits neurogenic inflammation postsynaptically

A non‐peptide NK₁‐receptor antagonist, RP 67580, inhibits neurogenic inflammation postsynaptically

Evaluation of Some Biological Activities of <i>Albizia lebbeck</i> Flowers