Effects of antitussive drugs on the activity of the recurrent laryngeal nerve in cats. (1/17)

Reflex responses in the recurrent laryngeal (RL) nerve to stimulation of superior laryngeal (SL) nerve and the effects of antitussive drugs on these reflex responses were studied in order to elucidate the site of action of these drugs in encephale isole cats. The RL nerve fibers were classified into four types by discharge patterns in respect to phases of artificial ventilation; type I: no spontaneous discharges, type II: discharges in phase with inflation of the lung, type III: discharges in phase with deflation of the lung, type IV: tonic discharges. Repetitive stimulation of the SL nerve elicited tonic burst discharges or short burst discharges in all types of RL nerve elicited tonic burst discharges or short burts discharges in all types of RL nerve, while the same procedure inhibited ongoing discharges of the type III and IV fibers only. The inhibited fibers tended to have slow conduction velocities (20-80 m/sec). Administration of antitussive drugs such as codeine, dextro methorphan and oxymetebanol as well as pentobarbital decreased the frequency of the after spike discharges in the RL nerves evoked following repetitive shocks to the SL nerve, but had no effects on the inhibition of RL nerve discharges evoked by the stimulation of the same nerve. The neuropharmacological implication of these findings as related to the cough reflex are discussed.  (+info)

Endogenous formation of morphine in human cells. (2/17)

Morphine is a plant (opium poppy)-derived alkaloid and one of the strongest known analgesic compounds. Studies from several laboratories have suggested that animal and human tissue or fluids contain trace amounts of morphine. Its origin in mammals has been believed to be of dietary origin. Here, we address the question of whether morphine is of endogenous origin or derived from exogenous sources. Benzylisoquinoline alkaloids present in human neuroblastoma cells (SH-SY5Y) and human pancreas carcinoma cells (DAN-G) were identified by GC/tandem MS (MS/MS) as norlaudanosoline (DAN-G), reticuline (DAN-G and SH-SY5Y), and morphine (10 nM, SH-SY5Y). The stereochemistry of reticuline was determined to be 1-(S). Growth of the SH-SY5Y cell line in the presence of (18)O(2) led to the [(18)O]-labeled morphine that had the molecular weight 4 mass units higher than if grown in (16)O(2), indicating the presence of two atoms of (18)O per molecule of morphine. Growth of DAN-G cells in an (18)O(2) atmosphere yielded norlaudanosoline and (S)-reticuline, both labeled at only two of the four oxygen atoms. This result clearly demonstrates that all three alkaloids are of biosynthetic origin and suggests that norlaudanosoline and (S)-reticuline are endogenous precursors of morphine. Feeding of [ring-(13)C(6)]-tyramine, [1-(13)C, N-(13)CH(3)]-(S)-reticuline and [N-CD(3)]-thebaine to the neuroblastoma cells led each to the position-specific labeling of morphine, as established by GC/MS/MS. Without doubt, human cells can produce the alkaloid morphine. The studies presented here serve as a platform for the exploration of the function of "endogenous morphine" in the neurosciences and immunosciences.  (+info)

Cinnamoyl derivatives of 7alpha-aminomethyl-6,14-endo-ethanotetrahydrothebaine and 7alpha-aminomethyl-6,14-endo-ethanotetrahydrooripavine and related opioid ligands. (3/17)

A new series of ligands has been synthesized where the cinnamoyl group of the 14-cinnamoylamino morphinones has been introduced to the 7alpha-substituent of the 6,14-bridged oripavine series. In vitro the compounds were mostly low efficacy partial agonists or antagonists with some selectivity for the mu opioid receptor, with evidence of micro efficacy in vivo. The similarity in SAR between these 6,14-bridged oripavines and the 14-cinnamoylamino series suggests a similar mode of interaction with the micro opioid receptor.  (+info)

Designation of oripavine as a basic class of controlled substance. Final rule. (4/17)

This is a final rule issued by the Drug Enforcement Administration (DEA) designating oripavine (3-O-demethylthebaine or 6,7,8,14-tetradehydro-4,5-alpha-epoxy-6-methoxy-17-methylmorphinan-3-ol) as a basic class in schedule II of the Controlled Substances Act (CSA). Although oripavine was not previously listed in schedule II of the CSA, it has been controlled in the United States as a derivative of thebaine and, as such, is controlled as a schedule II controlled substance which includes "Opium and opiate, and any salt, compound, derivative, or preparation of opium or opiate." Oripavine is a derivative of thebaine, a natural constituent of opium, hence oripavine has been and continues to be, by virtue of the definition of "narcotic drug", a schedule II controlled substance. International control of oripavine in schedule I of the 1961 Single Convention on Narcotic Drugs (1961 Convention) during the 50th session of the Commission on Narcotic Drugs (CND) in 2007 prompted the DEA to specifically designate oripavine as a basic class of controlled substance in schedule II of the CSA.  (+info)

Urinary excretion of morphine and biosynthetic precursors in mice. (5/17)

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The biosynthesis of papaverine proceeds via (S)-reticuline. (6/17)

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Consensus 3D model of mu-opioid receptor ligand efficacy based on a quantitative Conformationally Sampled Pharmacophore. (7/17)

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Fatality involving the ingestion of phenazepam and poppy seed tea. (8/17)

Phenazepam is a benzodiazepine derivative that has been in clinical use in Russia since 1978 and is not available by prescription in the United States; however, it is attainable through various internet websites, sold either as tablets or as a reference grade crystalline powder. Presented here is the case of a 42-year old Caucasian male who died as the result of combined phenazepam, morphine, codeine, and thebaine intoxication. A vial of white powder labeled "Phenazepam, Purity 99%, CAS No. 51753-57-2, Research Sample", a short straw, and several poppy seed pods were found on the scene. Investigation revealed that the decedent had a history of ordering medications over the internet and that he had consumed poppy seed tea prior to his death. Phenazepam, morphine, codeine, and thebaine were present in the blood at 386, 116, 85, and 72 ng/mL, respectively.  (+info)