The irreversible narcotic antagonistic and reversible agonistic properties of the fumaramate methyl ester derivative of naltrexone

Takemori, A. E.; Larson, D. L.; Portoghese, Philip S.

doi:10.1016/0014-2999(81)90355-1

Cited by 226 publications

(81 citation statements)

References 11 publications

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“…Effects ofpre-incubation with P-funaltrexamine on the potency ofagonists in the guinea-pig myenteric plexus Pre-incubation of the myenteric plexus with 100 nM Pfunaltrexamine for 30 min led to an increase in the IC50 value for morphine, confirming the findings of Takemori et al (1981). However, although morphine interacts mainly with gu-receptors, it has significant affinities for the 6-and K-receptors (Magnan et al, 1982).…”

Section: Resultssupporting

confidence: 71%

“…It has been shown that, in acute experiments, it is an agonist in the guinea-pig myenteric plexus-longitudinal muscle preparation. However, exposure of this tissue to 0-funaltrexamine for periods of 30 to 90 min causes an irreversible decrease in the agonist potencies of morphine and normorphine, which interact with p-receptors, without altering the agonist potency of ethylketazocine, which interacts with K-'Present address: Merck Sharp & Dohme Research Labortories, Neuroscience Research Centre, Terlings Park, Eastwick Road,Harlow,Essex CM20 2QR. receptors (Takemori et al, 1981;Huidobro-Toro et al, 1982;Ward et al, 1982b).…”

Section: Introductionmentioning

confidence: 99%

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Pre‐incubation of guinea‐pig myenteric plexus with β‐funaltrexamine: discrepancy between binding assays and bioassays

Corbett

Kosterlitz

McKnight

et al. 1985

British J Pharmacology

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1 The acute effects of P-funaltrexamine and the effects of pre-incubation with this compound were examined in five in vitro assay tissues and in selective binding assays in homogenates of guinea-pig brain and myenteric plexus. 4 These findings indicate that the effects of pre-incubation with P-funaltrexamine on agonist potency of the IA-receptor ligand are due to an interference with the coupling mechanism between the n-binding site and the effector system.

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Section: Resultssupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Pre‐incubation of guinea‐pig myenteric plexus with β‐funaltrexamine: discrepancy between binding assays and bioassays

Corbett

Kosterlitz

McKnight

et al. 1985

British J Pharmacology

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“…in the presence of (3-FNA to that in the absence of a-FNA was 5.0, 1.1 or 1.0, respectively ( Table 3), showing that (3-FNA was an irreversible mu antagonist and consistent with the previous report (7).…”

Section: Resultssupporting

confidence: 91%

Agonist and Antagonist Actions of Buprenorphine on Three Types of Opioid Receptor in Isolated Preparations

Kajiwara

Aoki

Ishii

et al. 1986

Japanese Journal of Pharmacology

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Abstract-Both agonist and antagonist actions of buprenorphine on isolated preparations were studied.The Ke (equilibrium dissociation constant) values of both naloxone and Mr 2266 [(-)-2-(3-furylmethyl)-5,9-diethyl-2'-hydroxy-6,7 henzomorphan] against buprenorphine and the ratio of IC50 (concentration of the drug to produce 50% inhibition of the twitch) value of buprenorphine after to before exposure of mouse vas deferens to 3-FNA (a-fumaramate methyl ester derivatives of naltrexone), an irreversible mu antagonist, suggest that buprenorphine acts as both a mu and kappa agonist on mouse vas deferens.The agonist effect of buprenorphine at relatively high doses on guinea-pig ileum and mouse vas deferens and the negative agonist effect on both rat and rabbit vas deferens indicate that buprenorphine acts as a partial agonist on isolated preparations.

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“…The DAGO-and PLO-I 7-induced PRL secretion during lactation was reversed by naloxone suggesting interaction with opioid receptors. Furthermore, pretreatment with the irreversible mu antagonist fl-FNA (28,29) abolished the effect of DAGO on PRL release. It is interesting to note that Pfeiffer and coworkers employed a dose of 10.0 nmol 8-FNA to inhibit the rise in plasma PRL evoked by 1.0 nmol DAGO in OVX rats (16).…”

Section: Discussionmentioning

confidence: 95%

Mu‐Selective Opioid Peptides Stimulate Prolactin Release in Lactating Rats

Baumann

Rabii

1990

J Neuroendocrinology

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The fact that opiates elicit prolactin secretion is well known. However, we have recently discovered that morphine does not stimulate prolactin release in lactating rats. The physiological basis for this alteration in opiate sensitivity during lactation is not known. Since morphine-induced prolactin secretion in male rats is mediated via the mu opioid receptor subtype, one possible explanation is that mi1 receptors are down-regulated during lactation. To address this possibility, the effects of mu opioid peptides on prolactin secretion were examined in lactating rats. The presumed mu-selective peptides DAGO ([D-Ala', Me-Phe4, Gly-01'1-enkephalin) and PLO-17 ("Me-Phe3, D-Pro4]-morphiceptin) were administered to primiparous lactating rats and the resulting hormone responses measured. Both DAGO and PLO-17 caused a rapid and significant rise in plasma prolactin during lactation. The prolactin-releasing effects of both peptides were naloxone reversible, suggesting involvement of opioid receptors. Moreover, the DAGO-induced secretion of prolactin could be completely abolished by pretreatment with the irreversible mu antagonist b-funaltrexamine. In lactating rats, DAGO and PLO-17 were poor growth hormone-releasing agents, providing further evidence for the mu specificity of these peptides. These results imply that during lactation, as in other reproductive states, mu opioid receptor sites are positively coupled to the prolactin secretory mechanism. Thus, the previously observed inability of morphine to elicit prolactin release in lactating rats cannot be explained on the basis of down-regulation of mu opioid receptors.The \timulatory effect of opioids on prolactin (PRL) release is well estaidished for several mammalian species, including man (1, 2). In tile rat, opioid antagonists such as naloxone, suppress basal and stimulus-induced PRL release suggesting that endogenous opiclid peptides (EOPs) may have an important role in the phqyiological regulation of PRL secretion (1, 2). Although most evidLmce points to central sites of EOP action (3-9, direct opioid effects at the level of the anterior pituitary cannot be completely m1eC out (6). Recently, the concept of multiple opioid receptors has gained wide acceptance, and many investigators have attempted to correlate specific neuroendocrine functions with particular opioid receptor subtypes (7-1 6).There is general agreement that at least three major opioid receptor populations are present: mu, kappa, and delta sites (17 19). The characterization of receptor subtypes is based largely on !he affinities of opioid ligands for particular binding sites in Vitvri Thus, morphine is the prototypical mu receptor agonist while enkephalin peptides interact preferentially with delta sites. Kelaocine-like drugs are potent, though non-selective, kappa agonists, and dynorphins appear to be the endogenous ligands for the kappa site (17,19). Unfortunately, determining the functional importance of specific opioid receptor subtypes has been difficult due to the fact that few opioid...

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The irreversible narcotic antagonistic and reversible agonistic properties of the fumaramate methyl ester derivative of naltrexone

Cited by 226 publications

References 11 publications

Pre‐incubation of guinea‐pig myenteric plexus with β‐funaltrexamine: discrepancy between binding assays and bioassays

Pre‐incubation of guinea‐pig myenteric plexus with β‐funaltrexamine: discrepancy between binding assays and bioassays

Agonist and Antagonist Actions of Buprenorphine on Three Types of Opioid Receptor in Isolated Preparations

Mu‐Selective Opioid Peptides Stimulate Prolactin Release in Lactating Rats

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