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Results for “Morphine Derivatives”

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At least 19 recordsLinked to original sources
PubMed2003

Molecular interactions between DPPC and morphine derivatives: a DSC and EPR study.

The interaction between different morphine derivatives (morphine, codeine, N-methyl-morphine, N-methyl-codeine) and alpha-L-dipalmitoyl phosphatidylcholine (DPPC) liposomes was studied with differential scanning calorimetry (DSC) and electron paramagnetic resonance (EPR) spectroscopy. Small unilamellar DPPC-liposomes with the given morphine-derivative were prepared by sonication. The size distribution of liposomes was checked by dynamic light scattering (DLS). The amount of entrapped morphine was determined spectrophotometrically. Our results indicate that the morphine and its derivatives principally interact with the lipid head groups, and this interaction leads to a decrease in the mobility of the polar head groups, especially in case of codeine and N-methyl-codeine.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2001

Reactions of morphine derivatives with phenyliodo(III)diacetate (PIDA): synthesis of new morphine analogues.

The reactions of morphine and its derivatives with phenyliodo(III)diacetate (PIDA) have been studied. This methodology has not been introduced to morphine alkaloids, despite the fact that such a strategy would ensure dearomatization of the electrophilic aromatic ring of morphine derivatives leading to nucleophilic ortho-quinoidal structures with potential pharmacological interest. The products, formed in regio- and diastereoselective or diastereospecific reactions, carry mixed-acetal or 1,3-dioxolane moieties. At low concentrations 6a has mu-opioid agonist character but in higher concentrations showed a non receptorial antagonist effect on isolated mouse vas deferens.

Acetates↗
PubMed1993

Synthesis and analgetic activity of nicotinic esters of morphine derivatives.

The synthesis of morphine nicotinates is described using nicotinyl chloride in the presence of pyridine. Isomorphine and isocodeine nicotinates were prepared from the corresponding morphine and codeine derivatives with nicotinic acid in the presence of triphenylphosphine and diethyl azodicarboxylate. Unexpectedly the reaction of 14-hydroxy-dihydromorphinone derivatives was anomalous, enolesters were formed. The analgetic activity of selected compounds was determined.

Analgesics, Opioid↗
PubMed1977

Interactions of narcotics and their antagonists with human serum esterase. VI: The behavior of 14-hydroxylated morphine derivatives.

Study of the interaction of 14-hydroxylated morphines and morphinans with human serum esterase revealed behavior similar to that of other morphine derivates as shown by similar acceleratory efficacies and affinity constants. However, 14-hydroxydihydro-6-morphinones showed anomalously low apparent affinities and anomalously high apparent efficacies, while at the same time seemingly interfering with the attachment of another drug to the enzyme. These anomalies are satisfactorily explained by assuming a second receptor site for which only the hydroxyketones have affinity and which interacts with the receptor site common to all opiates and opiate antagonists. Equations derived from this assumption allow to determine the parameters of the interactions of drugs with both receptor sites.

Esterases↗
PubMed1996

3-O-acetylmorphine-6-O-sulfate: a potent, centrally acting morphine derivative.

In view of the potent analgesia exhibited by the apparent structurally dissimilar morphine-6-O-glucuronide (M6G) and morphine-6-O-sulfate (M6S) conjugates of morphine, we have examined the effect of structural modification of M6S on analgesic activity, using the tail-flick test. Changes in the M6S structure were made that would affect the lipophilicity and polarity of the molecule. Subcutaneous (sc) and intracerebroventricular (ICV) administration of equimolar doses of morphine, M6S, 3-O-acetylmorphine-6-O-sulfate (M3A6S), 3-O-benzoylmorphine-6-O-sulfate (M3B6S), and 3-O-acetyl-N-methylmorphinium-6-O-sulfate (MM3A6S) were employed. M6S and M3A6S exhibited a longer duration of action and greater activity compared to morphine after SC and ICV administration. However, M3B6S and MM3A6S in doses equimolar to that of morphine were found to be inactive after both SC and ICV administration. In addition, M3A6S showed the highest potency in inhibiting electrically stimulated guinea pig ileum followed by M6S and M3B6S. Moreover, both M6S and M3A6S displayed a greater affinity than that of morphine to mu and kappa 3 receptor sites in guinea pig brain homogenate. In contrast, the nonanalgesic compounds M3B6S and MM3A6S showed weak receptor binding ability compared to morphine. These results indicate that lipophilicity alone is not a determinant of analgesic activity in these novel morphine derivatives. These modified effects of morphine by the conjugations at the 3- and 6-position, appear to be due to their altered interactions with opioid receptors.

Animals↗
PubMedDate not supplied

Some pharmacological properties of a newly synthesized morphine derivative, (-)-6 beta-acetylthiomorphine.

Some pharmacological properties of a newly synthesized morphine derivative, (-)-6 beta-acetylthiomorphine (AcS-morphine) were studied. AcS-morphine was about twice as potent as morphine in the inhibitory action of the twitch response of the guinea-pig ileal preparation to electrical stimulation. AcS-morphine, however, was 5 times as potent as morphine in the analgesic action in the rats. Both the effects of AcS-morphine were inhibited by naloxone, suggesting that the site of action of AcS-morphine is mu-receptors. It is interesting that 6 beta-isomer of AcS-morphine is 5 times as potent as 6 alpha-OH isomer of morphine in the analgesic action, because 6 alpha-OH isomer of morphine is much more potent than that of 6 beta-OH isomer. The effects of AcS-morphine on the specific binding of [3H]-naloxone, [3H]-ethylketocyclazocine and [3H]-D-Ala2-D-Leu5-enkephalin to the membrane fractions from the rat brain were tested. AcS-morphine was about 5 times as potent as morphine in its interactions with opioid receptors, as determined by the binding assay. AcS-morphine, as well as morphine, had a selectively high affinity to mu-receptors. The "sodium effect" and the "GTP effect" of AcS-morphine were almost the same as those of morphine. The dependence liability of AcS-morphine was preliminary tested in the guinea-pig ileal preparations treated with a high concentration of AcS-morphine for 24 hr. Results suggested that AcS-morphine is weaker than morphine in its dependence liability, though it seems almost certain that AcS-morphine does have this liability.

Analgesics↗
PubMed1977

Evidence for topographical analogy between methionine-enkephalin and morphine derivatives.

Analogues of the endogenous opiate-receptor ligand [5-methionine]enkephalin (H-Tyr-Gly-Gly-Phe-Met-OH) were designed and synthesized for the purpose of testing the proposed similarity in spatial structure between this peptide and morphine derivatives. In the bioassay (inhibition of electrically induced contractions of the mouse vas deferens) [1-O-methyltyrosine,5-methionine]enkephalin, [1-N-methyltyrosine,5-methionine]enkephalin, [4-tryptophan,5-methionine]enkephalin, and [5-methionine sulfoxide]enkephalin possess, respectively, 0.4, 21, 27, and 67% activity of [5-methionine]enkephalin. These morphinomimetic activities correlate well with the opiate receptor affinities determined by displacement of [3H]naloxone in a guinea pig brain membrane preparation. The effects of O-methylation of the tyrosine residue and N-methylation of the terminal amino group on biological activity and receptor affinity support the hypothesis that the latter two moieties in the peptide correspond to the phenol group and the tertiary nitrogen, respectively, in morphine. Determination of the efficiency of energy transfer from tyrosine in position 1 to tryptophan in position 4 in [4-tryptophan,5-methionine]enkephalin from both tyrosine fluorescence quenching and relative enhancement of tryptophan fluorescence by means of a modified procedure permitted the calculation of an average intramolecular tyrosine-tryptophan separation of 10.0 +/- 1.1 A. Inspection of CPK models showed excellent agreement between this value and both the intrafluorophore distance in the 4 leads to 1 and 5 leads to 2 hydrogen bonded betaI-bend models of [4-tryptophan,5-methionine]enkephalin (9-11 A) and the phenol-phenyl separation in the potent morphine derivative 7alpha-(1(R)-hydroxy-1-methyl-3-phenylpropyl)-6,14-endo-ethenotetrahydrooripavine (8-10.5 A). The ensemble of these findings suggests an analogous topography for [5-methionine]enkephalin and morphine-oripavine derivatives.

Animals↗
PubMed1981

[Value of morphine derivatives administered by the peridural route per- and postoperatively].

The existence of opiate receptors in the spinal cord led the authors to seek a clinical application. 1 - A peroperative injection of morphine was administered in 170 cases: 0.005 mg/kg of fentanyl in 105 cases and 0.05 mg/kg of morphine in 65 cases. In addition to usual surveillance (blood pressure, heart rate and central venous pressure), more extensive haemodynamic investigations were undertaken in 20 patients using a Swan-Ganz catheter. Blood concentrations (11 cases) and CSF concentrations (2 cases for each time of measurement) were determined in the case of fentanyl. In 20 patients (10 of whom had received fentanyl and 10 morphine) there was sophisticated cardio-respiratory surveillance postoperatively. 2 - 0.05 mg/kg or morphine (404 cases), 50 mg of pethidine (10 cases) and 0.1 mg of fentanyl (10 cases) were injected postoperatively. A comparison was made of the analgesia obtained. After three types of anaesthesia: epidural with bupivacaine with intubation (10 cases), halothane with intubation (10 cases) and neuroleptanaesthesia (10 cases), an injection was given of 0.05 mg/kg of morphine, with cardiorespiratory surveillance. Results were as follows: 1 - There were no significant variations in haemodynamic parameters peroperatively, indicative of adequate analgesia. Blood concentrations of fentanyl were as follows: 3.2 +/- 2.1 ng/ml after 10 minutes, 2 +/- 1.7 ng/ml after one hour, 1.4 +/- 1 ng/ml after two hours and 0.4 +/- 0.3 ng/ml after four hours. CSF concentrations were much higher; 34 ng/ml after one hour, 30 ng/ml after two and three hours and 25 ng/ml after four hours. No cardio-respiratory depression was seen after the peroperative injection of morphine. 2- The duration of analgesia following a postoperative injection of a morphine derivative was as follows: morphine 17.3 +/- 3.9 hours, pethidine 3.5 +/- 0.5 hours, and fentanyl 5.1 +/- 0.7 hours. The epidural injection of morphine after neuroleptoanaesthesia caused respiratory depression in two of the 10 cases, with a rise in pCO2 of 0.45 and 0.52 KPa. The results are discussed and compared with those of other authors. In conclusion, the authors emphasize the advantages of this method which makes it possible to obtain with smaller doses analgesia of longer duration than following a systemic injection of morphine, whilst at the same time decreasing the side effects.

Anesthesia, Epidural↗
PubMed1972

Coupling of a new, active morphine derivative to sepharose for affinity chromatography.

A new, pharmacologically active morphine derivative, 6-succinylmorphine, was synthesized. The properties of this compound and evidence for its structure are presented. Succinylmorphine was covalently coupled to ethylamino-Sepharose. Morphine-Sepharose containing up to 40 mug of morphine did not block the electrically stimulated contraction of isolated guinea pig ileum, but after alkaline hydrolysis of beads containing 2 mug of morphine the supernatant completely blocked contraction. This block was reversed by the specific morphine antagonist naloxone. Antibodies to morphine were removed from serum by morphine-Sepharose, but not by ethylamino-Sepharose, providing evidence of the efficacy of the beads for affinity chromatography.

Animals↗
PubMedDate not supplied

[Effect of morphine derivatives on the function of glucocorticoid receptors in shock].

The effects of opiate receptor agonists and antagonists on the function of glucocorticoid receptors in the hepatic cytosol were examined in male Wistar rats weighing 180-240 g. With the Scatchard analysis, in vitro experiments by using labelled ligands revealed that the pure opiate agonist morphine in the wide range of concentrations (0,01-10,0 mM) failed to affect the function Type II glucocorticoid receptors, though inhibited the function of Type III glucocorticoid receptors in the dose-dependent manner. Buprenorphine and diprenorphine depressed the function of Types II and III glucocorticoid receptors. Buterphanol, an opiate receptor antagonist-agonist, like naltrexone, an opiate receptor antagonist, decreased the function of Type III glucocorticoid receptors, but modulated that of Type II glucocorticoid receptors by lowering the association constant of the ligand-Type II glucocorticoid receptor complex, but by enhancing the density of Type II glucocorticoid receptors. In vivo studies established that butorphanol dose-dependently increased the density of Type II glucocorticoid receptors in the hepatic cytosol and elevating blood pressure in rat traumatic shock. Whether glucocorticoid receptors involve in the mechanism of the antishock effect of morphine derivatives is discussed in the paper.

Animals↗
PubMed2006

Non-competitive inhibitory activities of morphinan and morphine derivatives at the alpha 3 beta 4 Neuronal nicotinic acetylcholine receptor determined using nonlinear chromatography and chemometric techniques.

PURPOSE: A series of morphine and morphinan derivatives were chromatographed on a column containing immobilized cellular membranes from a cell line expressing the alpha 3 beta 4 neuronal nicotinic acetylcholine receptor (alpha 3 beta 4 nAChR). METHODS: The results were analyzed using chemometric and molecular modeling techniques in order to predict the noncompetitive inhibitory (NCI) activity of these compounds, the molecular basis for the predicted activity and the binding sites of the inhibitors. RESULTS: The data demonstrated that seven of seven morphinans were NCIs and bound in the central lumen of the nAChR while only 2 of 13 morphine derivatives had NCI activity and these compounds most likely bound at the quinacrine binding site on the nAChR. The predicted activities were confirmed using functional inhibition studies. CONCLUSIONS: The results indicate that this approach can be used to rapidly assess pharmacological activity and to guide new drug design.

Binding Sites↗