Drugs online research references
Biochem Pharmacol. 1996 May 3;51(9):1137-43.
Distinct responses of mouse hepatic CYP enzymes to corn oil and peroxisome proliferators.
Kojo A, Pellinen P, Juvonen R, Raunio H, Pelkonen O, Pasanen M.
Department of Pharmacology and Toxicology, University of Kuopio, Finland.
We studied the response of male DBA/2N mouse liver monooxygenases to acute (one-day) and subacute (7-day) exposure to clofibrate, gemfibrozil, and corn oil. The day following a single treatment with clofibrate (200 mg/kg), coumarin 7-hydroxylase (COH) activity decreased significantly (by 70%) with a concomitant decrease in the CYP2A4/5 protein and mRNA levels. The 7-day treatment schedule also decreased COH activity by only by 30%, though the levels of CYP2A4/5 protein and mRNA were still low. Treatment 1 and 7-day with clofibrate decreased 7-pentoxyresorufin O-dealkylase (PROD) activity by 40%. No changes were seen in testosterone 15 alpha-hydroxylase (T15 alpha OH) activity after 1 day of treatment with clofibrate but, after 7 days, it was decreased by 50%. Clofibrate treatment had no significant effects on testosterone 7 alpha-hydroxylase (T7 alpha OH), 7-ethoxyresorufin O-deethylase (EROD), or benzphetamine N-demethylase (BZDM) activities. Gemfibrozil (200 mg/kg) did not alter COH activity or CYP2A4/5 protein content after a single treatment, but a slight decrease was seen in the mRNA level. Treatment for 7 days significantly increased (2.5-fold) the activity and mRNA content but the amount of protein remained unchanged. Gemfibrozil enhanced (2-2.7-fold PROD and EROD (2-2.5-fold) activities by both treatments, whereas T15 alpha OH, T7 alpha OH, or BZDM activities were not significantly affected. Treatment with corn oil for 7 days significantly decreased (65%) COH activity and CYP2A4/5 protein and mRNA levels. PROD (55%) and T15 alpha OH (65%) activities were significantly decreased even after a single dose although injection for 7 days had no effect. Neither of the corn oil schedules had any marked effect on T7 alpha OH, EROD, or BZDM activities. These results demonstrate: 1. a decrease in the expression of CYP2A4/5 gene by clofibrate and corn oil; 2. substantial differences within the CYP2A subfamily in their responses to corn oil, clofibrate, and gemfibrozil; and 3. distinct responses of other xenobiotic metabolizing CYP subfamily enzymes to clofibrate and gemfibrozil.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8645335&dopt=Abstract
Arzneimittelforschung. 1996 Oct;46(10):981-5.
Synthesis and antihyperlipaemic activity of some 2-aminomethyl-3-aryl-5,6,7,8-tetrahydrobenzo(b)/5,6-dimethylthieno++ +(2,3- d) -pyrimidin-4-ones.
Gadad AK, Kapsi SG, Anegundi RI, Pattan SR, Mahajanshetti CS, Shishoo CJ.
Department of Medicinal Chemistry, College of Pharmacy, J.N. Medical College, Belgaum, Karnatak (India).
A series of 2-aminomethyl-3-aryl-5,6,7,8-tetrahydrobenzo(b)/5,6-dimethylthieno (2,3-d) pyrimidin-4-ones (IX) were prepared by the displacement reaction between various amines and 2-chloromethyl-3-aryl-5,6, 7,8-tetrahydrobenzo(b)/5, 6-dimethylthieno(2, 3-d) pyrimidin-4-ones (VIII), which are obtained by the cyclization of corresponding chloroacetylamino derivatives (VII) under acidic condition. Compounds VII were obtained by the interaction of VI and chloroacetylchloride in glacial acetic acid. Compounds VIII were converted to corresponding 2-acetoxymethyl derivatives (X) with potassium acetate in glacial acetic acid. Selected compounds were screened for antihyperlipaemic activity in albino rats, whereby most of these compounds were found to be active. The serum cholesterol and triglyceride lowering activities exhibited by compounds 1 and 3 were found to be comparable to that of gemfibrozil. Compounds 1 and 3 were also found to be safe as indicated by their acute toxicity study.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8931892&dopt=Abstract
J Assoc Physicians India. 1990 Feb;38(2):136-40.
Gemfibrozil in hyperlipidaemia: an open, single blind trial.
Varthakavi PK, Turakhia DP, Sharma SS, Salgaonkar DS, Nihalani KD, Joshi VR.
Department of Cardiology, T.N. Medical College, Bombay.
The efficacy of Gemfibrozil on S. lipid levels was studied in 36 middle aged subjects with type IIA, IIB, IV hyperlipidemia. Gemfibrozil was well tolerated in the dose of 1200 mg/day and no dropouts were attributable to its use. An overall reduction in total cholesterol (39.91%), total triglycerides (71.10%), VLDL triglycerides (62.97%). LDL cholesterol (45.57%) and apolipoprotein B levels (26.83%) were observed at 24 weeks. At the same time HDL cholesterol, and apolipoprotein A levels showed increases by 26.23% and 53.67% respectively. It is concluded that Gemfibrozil is an effective lipid lowering agent. Further long term studies are necessary to determine its optimal dosage and its long term safety in Indian subjects.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2380132&dopt=Abstract
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