Levbid
Regulatory role of 5-HT and muscarinic receptor antagonists on the migrating myoelectric complex in rats.

Axelsson LG, Wallin B, Gillberg PG, Sjoberg B, Soderberg C, Hellstrom PM.

Section of Gastroenterology and Hepatology, Department of Internal Medicine, Karolinska Hospital, Karolinska Institutet, SE-171 76 Stockholm, Sweden.

The 5-HT(3) and 5-HT(4) receptor antagonists alosetron and piboserod, and the muscarinic receptor antagonists PNU-171990A (2-(diisopropylamino)ethyl 1-phenylcyclopentanecarboxylate, hydrochloride) and PNU-174708A (2-(diisopropylamino)ethyl 1-phenylcyclohexanecarboxylate) were studied by electromyography, defining the migrating myoelectric complex (MMC) after i.v. administration in conscious rats. Alosetron prolonged the MMC cycle length from 16.6 to maximally 30.4 min at the dose 0.5 mg kg(-1). Piboserod promptly abolished MMC pattern and prolonged cycle length from 16.5 to >60 min at 0.5 mg kg(-1). PNU-171990A and PNU-174708A had no effect on basal cycle length up to a dose of 20 mg kg(-1). In controls, saline did not change the MMC pattern, while L-hyoscyamine at the same dose, 20 mg kg(-1), prolonged cycle length from 17.6 to 29.0 min. None of the drugs affected duration or propagation velocity of phase III of MMC. Blockade of 5-HT(4) receptors seems to exert a powerful inhibitory effect on motility, 5-HT(3) receptor blockade is less efficient and muscarinic receptor blockade has low efficacy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12706477&dopt=Abstract hyoscyamine Levbid SL



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Alkaloids in plants and root cultures of Atropa belladonna overexpressing putrescine N-methyltransferase.

Rothe G, Hachiya A, Yamada Y, Hashimoto T, Drager B.

Institute of Pharmaceutical Biology, Martin-Luther-University Halle-Wittenberg, Hoher Weg 8, D-06120 Halle/Saale, Germany.

Putrescine N-methyltransferase (PMT) is the first alkaloid-specific enzyme for nicotine and tropane alkaloid formation. The pmt gene from Nicotiana tabacum was fused to the CaMV 35S promoter and integrated into the Atropa belladonna genome. Transgenic plants and derived root cultures were analysed for gene expression and for levels of alkaloids and their precursors. Scopolamine, hyoscyamine, tropine, pseudotropine, tropinone, and calystegines were found unaltered or somewhat decreased in pmt-overexpressing lines compared to controls. When root cultures were treated with 5% sucrose, calystegine levels were elevated in control roots, but were not affected in pmt-overexpressing roots. 1 microM auxin reduced calystegine levels in control roots, while in pmt-overexpressing roots all alkaloids remained unaltered. Expression level of pmt alone is apparently not limiting for tropane alkaloid formation in A. belladonna.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12885861&dopt=Abstract hyoscyamine Levbid SL



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The effect of nitrate and ammonium concentrations on growth and alkaloid accumulation of Atropa belladonna hairy roots.

Bensaddek L, Gillet F, Saucedo JE, Fliniaux MA.

Laboratoire de Phytotechnologie, Faculte de Pharmacie d'Amiens, Universite de Picardie Jules Verne, 1, rue des Louvels, 80037 Cedex 1, Amiens, France. lamine.bensaddek u-picardie.fr

The growth, the alkaloid production, as well as the scopolamine/hyoscyamine ratio of two clones of belladonna hairy roots were studied. The effects of nitrate and ammonium concentrations on these cultures were investigated. A rise in ammonium concentration caused the decline of the hairy roots, while nitrate had a marked effect on the alkaloid content. The alkaloid production obtained with 15.8 mM of NO3- and 20.5 mM of NH4+ was 1.2-1.4 times higher than that obtained when the roots were grown in the standard Murashige and Skoog medium (MS medium, 39.5 mM of NO3- and 20.5 mM of NH4+). The nitrate and ammonium concentrations in the culture medium also had a strong influence on the scopolamine/hyoscyamine ratio. When nitrate or ammonium concentrations were raised, that ratio also was increased 2-3-fold. The hairy root clones originating from transformations with two distinct strains of Agrobacterium had similar responses.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11164960&dopt=Abstract hyoscyamine Levbid SL



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Tropane alkaloid production by shoot culture of Duboisia myoporoides R. Br.

Khanam N, Khoo C, Close R, Khan AG.

Department of Biological Sciences, University of Western Sydney, Campbelltown, NSW, Australia. dk.williams uws.edu.au

This work demonstrates the presence of hyoscyamine and scopolamine at different stages of shoot regeneration from non-organogenic and organogenic calli. The 11-week-old non-organogenic calli contained 0.41+/-0.03 and 0.23+/-0.02 microg g(-1) dry wt hyoscyamine and scopolamine respectively. However, no root meristem was found in the calli. The alkaloids were absent in 2-week-old organogenic calli. The shoot-buds induced on the non-organogenic and organogenic calli did not contain these alkaloids. Hyoscyamine and scopolamine contents of the 6-week-old non-rooted shoots regenerated from non-organogenic calli were 7.8+/-0.1 and 6.5+/-0.4 microg g(-1) dry wt respectively and those in the 9-week-old non-rooted shoot regenerated from organogenic calli were 38.5+/-0.4 and 3.6+/-0.1 microg g(-1) dry wt respectively. Hyoscyamine and scopolamine contents of the 4-week-old roots regenerated from non-organogenic and organogenic calli were higher than those in the non-rooted shoots. Since the presence of hyoscyamine and scopolamine in the non-rooted shoot depends on the stage of differentiation, manipulation of culture environment may improve hyoscyamine and scopolamine contents of the non-rooted shoots.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11198820&dopt=Abstract hyoscyamine Levbid SL



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HPLC evaluation of diclofenac in transdermal therapeutic preparations.

Klimes J, Sochor J, Dolezal P, Korner J.

Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy, Charles University, Heyrovskeho 1203, 50005, Hradec Kralove, Czech Republic. klimes faf.cuni.cz

High-performance liquid chromatography (HPLC) was selected for analytical evaluation of sodium diclofenac in original transdermal therapeutic preparations containing adjuvant substances (capsaicin, hyoscyamine). After isolation from laminated adhesive patches, diclofenac was analysed on columns with reversed phase, using the mobile phase ethanol and phosphate buffer (pH 6.5) with an addition of tetrabutylammonium iodide and detection at 284 nm. Not only the total amount of diclofenac in the patch was evaluated, but HPLC methodology was also employed to select a suitable acceptor medium for permeation experiments. In patches manufactured in the tested series, HPLC was also employed to examine the release of diclofenac and its in vitro permeation through the human skin.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11292551&dopt=Abstract hyoscyamine Levbid SL