Peripheral antinociceptive effects of N-methyl morphine

Smith, T.W.; Buchan, Peter; Parsons, D.N.; Wilkinson, S.

doi:10.1016/0024-3205(82)90343-5

Cited by 110 publications

(42 citation statements)

References 4 publications

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“…The effect of morphine appeared to be mediated through interaction with classical opiate receptors since intravenous administration of low doses of the opiate antagonist, naloxone, abolished this response. In addition, the peripherally-acting quaternary antagonist, N-methyl nalorphine (Smith et al, 1982) also substantially inhibited the potentiating action of morphine, giving further support to a peripheral site of action of the opioids in this model. Although the opioid receptors have not been fully characterised, the specificity of morphine, naloxone and N-methyl nalorphine (Magan et al, 1982) suggest the involvement of y receptors in this mechanism.…”

Section: Discussionmentioning

confidence: 61%

“…Furthermore, studies on pain and analgesia have demonstrated that opioids can affect afferent sensory neurones by an action at peripheral sites (Ferreira & Nakamura, 1979;Smith et al, 1982;Ferreira et al, 1984;Russell et al, 1987). The suggestion that local afferent neurones can modulate gastric mucosal integrity thus raises the possibility that opioids could affect the response to mucosal injury, by a peripheral action on such neuronal mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…This effect appears to be exerted at peripherally-located opioid receptors since the quaternary analogue, N-methyl morphine, which does not penetrate the blood-brain barrier and thus acts at peripheral sites (Smith et al, 1982), likewise substantially augmented Paf-induced damage. The effect of morphine appeared to be mediated through interaction with classical opiate receptors since intravenous administration of low doses of the opiate antagonist, naloxone, abolished this response.…”

Section: Discussionmentioning

confidence: 99%

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Local opioid‐sensitive afferent sensory neurones in the modulation of gastric damage induced by Paf

Esplugues

Whittle

Moncada

1989

British J Pharmacology

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The role of local sensory neurones in modulating the extent of gastric mucosal damage induced by close‐arterial infusion of platelet‐activating factor (Paf 50 ng kg−1 min−1 for 10 min) has been investigated in the anaesthetized rat. Local intra‐arterial infusion of the neurotoxin, tetrodotoxin (TTX), substantially augmented the mucosal damage induced by Paf, as assessed by both macroscopic and histological techniques. In rats pretreated with capsaicin 2 weeks prior to study, to induce a functional ablation of primary afferent neurones, gastric damage induced by Paf was significantly augmented. Administration of morphine (0.75–3 mg kg−1 i.v.) or its peripherally acting quaternary analogue, N‐methyl morphine (15 mg kg−1 i.v.), also significantly enhanced the gastric damage induced by Paf. The potentiation by morphine of Paf‐induced gastric damage was inhibited by administration of the opioid antagonists, naloxone (1 mg kg−1 i.v.) or the peripherally acting N‐methyl nalorphine (3 mg kg−1 i.v.). Administration of TTX or morphine alone, or pretreatment with capsaicin did not induce any detectable mucosal damage, suggesting that interference with local sensory neuronal activity itself does not directly induce mucosal disruption. These results indicate that peripheral opiate‐sensitive afferent sensory neurones play a physiological defensive role in the mucosa, attenuating the extent of gastric damage induced by Paf.

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Local opioid‐sensitive afferent sensory neurones in the modulation of gastric damage induced by Paf

Esplugues

Whittle

Moncada

1989

British J Pharmacology

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“…administration was used in the hot-plate test as this method involves a supraspinal response whilst the i.p. route was used for the abdominal constriction test which is sensitive to antinociceptive agents which act peripherally (Smith et al, 1982). When investigating the possible involvement of opioids, naloxone was administered by the same route as the arginine vasopressin.…”

Section: Nociceptionmentioning

confidence: 99%

Vasopressin and stress‐induced antinociception in the mouse

Hart

Oluyomi

1990

British J Pharmacology

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1 Arginine vasopressin produced antinociception in the hot-plate test after intracerebroventricular injection (0.5 yg) and in the acetic acid abdominal constriction test after intraperitoneal injection (0.1 mg kg-1). 2 The antinociception produced by arginine vasopressin was sensitive to deamino(CH2),Tyr(Me) arginine vasopressin (0.5 pg i.c.v.; 0.1 mg kg-l i.p.) but not to naloxone (5 pg i.c.v.; 2mg kg-l i.p.) 3 Arginine vasopressin when administered by the intracerebroventricular route, but not by the intraperitoneal route, produced characteristic behaviour which was sensitive to deamino(CH2)5Tyr(Me) arginine vasopressin (0.5 pg, i.c.v.).4 A 3min swim at 20'C produced antinociception on the hot-plate which was sensitive to naloxone (0.4 mg kg-1, i.p.) but not to deamino(CH2).Tyr(Me) arginine vasopressin (0.5 pg, i.c.v.).5 The reduction in the number of acetic acid-induced abdominal constrictions produced by a 30s swim at 30°C was not sensitive to either naloxone (2mgkg-1, i.p.) or deamino(CH2).Tyr(Me) arginine vasopressin (0.1 mg kg-1, i.p.). 6 Arginine vasopressin, at high doses, is antinociceptive in the mouse but does not appear to mediate stress-induced antinociception in this species.

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“…Local activity of the opioids when applied locally is reversed by naloxone [6,17,20,21,22] is dose-dependent and stereospecific. Most studies indicate that mu receptor ligands are the most important agonists, but delta and kappa-ligands are also active, depending upon the nature of the noxious stimuli [23].…”

Section: Discussionmentioning

confidence: 99%

The efficacy of locally applied morphine in post‐operative pain after bilateral third molar surgery.

Moore

Seymour

Gilroy

et al. 1994

Brit J Clinical Pharma

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1. Recent evidence has hinted at a peripheral site of action of morphine analgesic efficacy. 2. Previous studies by the same authors have developed a model for testing local analgesic efficacy by placing drugs into tooth sockets after third molar surgery. 3. The present studies test the hypothesis of local morphine activity at two dosage concentrations, 100 ng ml‐1 and 100 micrograms ml‐1 after third molar surgery. 4. No significant analgesic efficacy was found at either dose when compared with placebo.

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Peripheral antinociceptive effects of N-methyl morphine

Cited by 110 publications

References 4 publications

Local opioid‐sensitive afferent sensory neurones in the modulation of gastric damage induced by Paf

Local opioid‐sensitive afferent sensory neurones in the modulation of gastric damage induced by Paf

Vasopressin and stress‐induced antinociception in the mouse

The efficacy of locally applied morphine in post‐operative pain after bilateral third molar surgery.

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