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M. Sattari PA. Routledge SO. Mashayekhi 《Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences》2011,19(6):412-416
Background and the purpose of the study
Morphine-6-glucuronide (M6G) is a potent metabolite of morphine which has high penetration into the brain despite its high polarity, which could be the result of an active transport system involved in M6G transport through blood brain barrier. Examples of such transporters are p-glycoprotein (PGP), probenecid-sensitive transport mechanism, multidrug resistance related protein 1-3, the organic anion transporter family, and the organic anion transporter polypeptide family. The aim of present study was to elucidate the mechanisms involved in transporting morphine''s potent metabolite, M6G.Methods
M6G permeability via two cell lines; MDCKII and MDCK-PGP, was compared with that of sucrose. M6G transport was examined in different concentrations and in the presence of inhibitors of different transport systems such as cyclosporine, digoxin and probenecid. M6G concentration was measured using ELISA assay. The method was sensitive, reliable and reproducible.Results
The results confirmed that M6G could cross a layer of MDCK II or MDR-PGP cells more than sucrose could. It was also observed that M6G is a PGP transporter substrate. Its permeability was increased by the use of a PGP expressed cell line, and also in the presence of a strong PGP inhibitor. Digoxin related transporters such as Oatp2 may also involved in transport of M6G. M6G seemed to be a glucose transporter 1 substrate, but was not a substrate to probenecid sensitive transporters.Major conclusion
It is concluded that different transporters are responsible for M6G transports via different membrane, which could have effects on its pharmacokinetics or pharmacodynamics. 相似文献123.
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Seven young extrinsic asthmatics participated in an open, pilot study to determine the protective effect of a selective 5-hydroxytryptamine (5-HT) blocking agent, ketanserin, on exercise induced asthma. ketanserin in a dose of 10 mg given intravenously 20 min before exercise altered the basal bronchomotor tone in only 1 of 6 subjects and offered partial protection against exercise-induced bronchoconstriction in 1 of 5 asthmatics with no overall effect in the group. All patients experienced sleepiness after administration of ketanserin and one had bradycardia with hypotension. The ineffectiveness of ketanserin suggests indirectly that serotonin has a limited role in the pathogenesis of exercise-induced asthma. 相似文献
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Twelve patients with intractable rheumatoid arthritis were treatedwith antilymphocyte globulin (ALG), prednisolone and a cytotoxicagent, usually azathioprine, and were followed for 1 year. Therewas a significant (p < 0.05) improvement in the mean scorefor early-morning stiffness, grip strength and the severityof nodules and vasculitis at 6 weeks and 3 months when comparedto the initial visit. However, in most patients, this benefitwas not sustained despite continued cytotoxic and steroid therapy.A rise in the haemoglobin and fall in ESR was maintained throughoutthe study period. 相似文献