Quantitative studies on the antagonism by naloxone of some narcotic and narcotic‐antagonist analgesics

Smits, Stephen E.; Takemori, A. E.

doi:10.1111/j.1476-5381.1970.tb10370.x

Cited by 86 publications

(26 citation statements)

References 14 publications

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“…All of the results of the interaction studies between meptazinol and naloxone support the view that the former drug's mechanism of action involves an effect at opiate receptors. Although naloxone was a more potent antagonist of responses to morphine than of those to meptazinol, this is consistent with other evidence that partial agonists are less susceptible to naloxone challenge than are opioid agonists of the morphine type (Smits & Takemori, 1970). Also, the general profile of action of meptazinol in vivo resembles that of established agonist/antagonist analgesics (Stephens et al, 1978) In contrast to the relatively consistent effects of naloxone, the action of scopolamine on responses to meptazinol differed substantially according to the antinociceptive test and species used.…”

Section: Discussionsupporting

confidence: 75%

The antinociceptive activity of meptazinol depends on both opiate and cholinergic mechanisms

Bill

Hartley

Stephens

et al. 1983

British J Pharmacology

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Antinociceptive responses to meptazinol, morphine and oxotremorine and the effects of pretreatment with naloxone or scopolamine on these responses in mice and rats, were examined. 2 Meptazinol evoked larger increases in nociceptive thresholds in the mouse than in the rat, whereas morphine induced large increases in both species. Oxotremorine was both a more potent and a more effective antinociceptive agent in the mouse than in the rat. 3 Antinociceptive responses to meptazinol were consistently inhibited in animals pretreated with naloxone, whereas scopolamine attenuated the effects of meptazinol in some, particularly the mouse tail immersion test, but not in all of the procedures used. 4 Naloxone inhibited all antinociceptive responses to morphine, and scopolamine inhibited all responses to oxotremorine. However, there was no significant interaction between naloxone and oxotremorine or between scopolamine and various opioid analgesic agents. 5 These results indicate that meptazinol, unlike established opioid drugs, may induce antinociception by a dual action on opiate and cholinergic mechanisms.

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Section: Discussionsupporting

confidence: 75%

The antinociceptive activity of meptazinol depends on both opiate and cholinergic mechanisms

Bill

Hartley

Stephens

et al. 1983

British J Pharmacology

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“…The pA2 value we obtained for the morphine-naloxone interaction in the rat colon is consistent with that found by Takemori, Kupferberg & Miller (1969), Smits & Takemori (1970) and Harris, Loh & Way (1976b) for antinociception in rodents, but slightly lower than that reported for inhibition of electrically induced contractions in the guinea-pig ileum (Kosterlitz & Watt, 1968;Vaught & Takemori, 1978;HuidobroToro et al, 1981). Perhaps these differences in pA2 values could be interpreted as evidence in support of the concept of heterogeneity of opiate receptors in the peripheral system as suggested by Lord, Waterfield, Hughes & Kosterlitz, 1977.…”

Section: Discussionsupporting

confidence: 79%

Contractile Effect of Morphine and Related Opioid Alkaloids, Β‐endorphin and Methionine Enkephalin on the Isolated Colon From Long Evans Rats

Huidobro‐Toro

Way

1981

British J Pharmacology

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1 Morphine and related synthetic surrogates as well as P-endorphin and methionine enkephalin caused a contractile response of the longitudinal musculature of the terminal colon of Long Evans rats. 2 The muscular contraction caused by the narcotic analgesics exhibited stereospecificity, with levorphanol being about 50 times more potent than dextrorphan and (-)-methadone 4 times more potent than (+ )-methadone. In addition, the rank order in potency of a homologous series of N-alkyl substituted norketobemidones demonstrated that the activity of these compounds in eliciting contractile responses corresponded to that for analgesic efficacy in the rat and also correlated to the ability of these derivatives to inhibit the muscular twitch evoked by electrical stimulation of the guinea-pig ileum. 3 Naloxone blocked the contractile response of the opiates following competitive kinetics; the naloxone pA2 values for morphine, etorphine, levorphanol and methadone were very close, in spite of the marked differences in potency of these agents. 4 The contractile effect of morphine on the rat colon was abolished by incubation of the tissues with tetrodotoxin 2.0 x 10-7M or by decreasing the external Ca2+ level 100 fold. Increasing the external Ca2+ concentration caused an apparent non-competitive antagonism of the response to morphine. 5 Pretreatment of the tissues with hexamethonium 8.3 x 10-5M caused a modest antagonism of the morphine effect while atropine 5.8 x 10-7M did not significantly modify the morphine contractile effect. In contrast, methysergide 1i-5 M caused a 10 fold increase in the morphine EC50.6 Colons from rats rendered tolerant-dependent on morphine were markedly less sensitive to the contractile effects of morphine than those from placebo-treated controls. Tolerance to morphine was also accompanied by an increased sensitivity to the contractile effects of 5-hydroxytryptamine (5-HT).7 A marked increase in the spontaneous muscular activity of segments of the terminal colon of rats chronically treated with morphine was found to occur upon removal of the residual morphine in the tissues by repetitive washings. The spontaneous activity was arrested by applications of morphine, suggesting that physical dependence can be demonstrated in vitro in this particular preparation. 8 It is concluded that the opiate-induced contractile response is mediated via stereospecific, naloxone-sensitive, opiate receptors and that the muscular response involves the activation of a 5-HT neurone in the nerve terminals of the colon.

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“…The potency ratios for Straub tail in combi nation with 3 and 10 pg U-50,488H were 0.175 and 0.044, respectively. (27,28). It is essential to have highly selective opioid antagonists as pharmacological tools to investigate the pharmacological effects that are mediated by different types of opioid receptors.…”

Section: Discussionmentioning

confidence: 99%

The Cytosolic Acidification in Rat Parotid Cells Is Associated with an Increase in Cytosolic Ca2+ Concentration

Narita

Takahashi

Takamori

et al. 1993

Japanese Journal of Pharmacology

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Quantitative studies on the antagonism by naloxone of some narcotic and narcotic‐antagonist analgesics

Cited by 86 publications

References 14 publications

The antinociceptive activity of meptazinol depends on both opiate and cholinergic mechanisms

The antinociceptive activity of meptazinol depends on both opiate and cholinergic mechanisms

Contractile Effect of Morphine and Related Opioid Alkaloids, Β‐endorphin and Methionine Enkephalin on the Isolated Colon From Long Evans Rats

The Cytosolic Acidification in Rat Parotid Cells Is Associated with an Increase in Cytosolic Ca2+ Concentration

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