Opiate receptor binding of nicomorphine and its hydrolysis products in rat brain

Lobbezoo, Marinus W.; Rooy, H.H. Van; Wijngaarden, I. Van; Soudijn, W.

doi:10.1016/0014-2999(82)90515-5

Cited by 11 publications

(2 citation statements)

References 7 publications

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“…[7][8][9][10][11][12] In the present study, the morphine 3-esters, when compared with the parent compound, were up to 4600-, 300-, and 9300-fold less potent for binding to µ-, δ-, and κ-opioid receptors, respectively ( Table 4). [7][8][9][10][11][12] In the present study, the morphine 3-esters, when compared with the parent compound, were up to 4600-, 300-, and 9300-fold less potent for binding to µ-, δ-, and κ-opioid receptors, respectively ( Table 4).…”

Section: Resultsmentioning

confidence: 50%

Synthesis, Opioid Receptor Affinity, and Enzymatic Hydrolysis of Sterically Hindered Morphine 3-Esters*

Mignat

Heber

Schlicht

et al. 1996

Journal of Pharmaceutical Sciences

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With the intention of preparing prodrugs, 10 morphine 3-esters were synthesized and evaluated in vitro for opioid receptor binding and enzymatic hydrolysis. The results of binding assays performed on homogenates of guinea pig brain demonstrate a loss in affinity of morphine to mu-, delta-, and kappa-receptors by esterification at the 3-position. The conversion of the esters to morphine was determined in human plasma by HPLC analysis. The half-lives of hydrolysis ranged from 0.5 to > 300 h. The investigations indicate that esterification at the 3-position results in morphine prodrugs with variable hydrolytic stability. Sterically hindered morphine 3-esters may be a promising approach to manipulate the rate of release of morphine.

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Section: Resultsmentioning

confidence: 50%

Synthesis, Opioid Receptor Affinity, and Enzymatic Hydrolysis of Sterically Hindered Morphine 3-Esters*

Mignat

Heber

Schlicht

et al. 1996

Journal of Pharmaceutical Sciences

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“…Nicomorphine (Vilan | is the 3,6-dinicotinoyl ester of morphine, which can be considered as a morphinomimetic prodrug that is approximately equipotent to morphine [1]. However, its onset is quicker, its duration of action longer, and it shows fewer side-effects than morphine.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of nicomorphine and its metabolites in man after epidural administration

Koopman-Kimenai¹,

Vree²,

Hasenbos

et al. 1991

Pharmaceutisch Weekblad Scientific Edition

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In ten patients who received an epidural injection of 15 mg of nicomorphine, the compound was relatively slowly released from the epidural space and was found in plasma for approximately 1.5 h. Nicomorphine is relatively slowly metabolized into 6-nicotinoylmorphine and morphine. The rate of release is patient-dependent. The relative AUC values are 15.3% for nicomorphine, 23.9% for 6-nicotinoylmorphine and 60.8% for morphine. The mean clinical effect lasts for 18.2 +/- 10.1 h.

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Pharmacokinetics of epidurally administered nicomorphine with its metabolites and glucuronide conjugates in patients undergoing pulmonary surgery during combined epidural local anaesthetic block and general anaesthesia

Koopman-Kimenai

Vree

Booij

et al. 1995

Biopharm & Drug Disp

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After epidural administration of 15 mg 3, 6-dinicotinoylmorphine (nicomorphine) in 10 patients undergoing pulmonary surgery, the parent compound was quickly metabolized into the metabolites 6-mononicotinoylmorphine and morphine. The mean apparent half-lives (+/- SD) of elimination were 10 min (0.165 h +/- 0.053 h) for 3,6-dinicotinoylmorphine and 1.77 h +/- 1.23 h for 6-mononicotinoylmorphine. Morphine is subsequently metabolized into morphine-3-glucuronide and morphine-6-glucuronide. The apparent half-lives of morphine, morphine-3-glucuronide, and morphine-6-glucuronide are similar: 3.63 h +/- 1.63 h, 4.10 h +/- 0.57 h, and 4.20 h +/- 1.64 h respectively. The possible glucuronide conjugate of 6-mononicotinoylmorphine was not detected. The prodrug 3,6-dinicotinoylmorphine was biotransformed into three active compounds: 6-mononicotinoylmorphine, morphine, and morphine-6-glucuronide.

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Opiate receptor binding of nicomorphine and its hydrolysis products in rat brain

Cited by 11 publications

References 7 publications

Synthesis, Opioid Receptor Affinity, and Enzymatic Hydrolysis of Sterically Hindered Morphine 3-Esters*

Synthesis, Opioid Receptor Affinity, and Enzymatic Hydrolysis of Sterically Hindered Morphine 3-Esters*

Pharmacokinetics of nicomorphine and its metabolites in man after epidural administration

Pharmacokinetics of epidurally administered nicomorphine with its metabolites and glucuronide conjugates in patients undergoing pulmonary surgery during combined epidural local anaesthetic block and general anaesthesia

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