Drugs online research references
Neuropharmacology. 2003 Dec;45(7):935-44.
Comparison of effects of dual transporter inhibitors on monoamine transporters and extracellular levels in rats.
Koch S, Hemrick-Luecke SK, Thompson LK, Evans DC, Threlkeld PG, Nelson DL, Perry KW, Bymaster FP.
Lilly Neuroscience Research Division, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Compounds that block both serotonin (5-HT) and norepinephrine (NE) transporters have been proposed to have improved antidepressant efficacy. We compared the ability of four dual transporter inhibitors-chlorimipramine, duloxetine, milnacipran and venlafaxine-to block monoamine transporters in vitro and in vivo and increase extracellular monoamines in rat brain. Inhibition of radioligand binding to clonal human monoamine transporters in vitro and in vivo in rats was determined. Extracellular concentrations of 5-HT and NE in rat prefrontal cortex (PFC) were quantified using the microdialysis technique. All compounds blocked binding to human 5-HT and NE transporters, although chlorimipramine and venlafaxine had markedly greater affinity for 5-HT than NE transporters. In vivo, chlorimipramine and duloxetine potently blocked both transporters, milnacipran blocked both with lower potency and venlafaxine only blocked the 5-HT transporter. Chlorimipramine and duloxetine increased robustly and approximately equally monoamine extracellular concentrations. Milnacipran produced only small increases in NE, whereas venlafaxine increased 5-HT markedly at the lower doses and both monoamines at high doses. Thus, the dual transporter inhibitors blocked 5-HT and NE transporters in vitro and in vivo with varying potency. Chlorimipramine, duloxetine, and high dose venlafaxine acted as dual transporter inhibitors in rat PFC and increased extracellular concentrations of the monoamines, indicating functional dual transporter inhibition.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14573386&dopt=Abstract
kwd match effexor online literature
Psychopharmacology (Berl). 1996 Dec;128(4):398-407.
Phenacetin O-deethylation by human liver microsomes in vitro: inhibition by chemical probes, SSRI antidepressants, nefazodone and venlafaxine.
von Moltke LL, Greenblatt DJ, Duan SX, Schmider J, Kudchadker L, Fogelman SM, Harmatz JS, Shader RI.
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA.
Biotransformation of phenacetin via O-deethylation to acetaminophen, an index reaction reflecting activity of Cytochrome P450-1A2, was studied in microsomal preparations from a series of human livers. Acetaminophen formation was consistent with a double Michaelis-Menten system, with low-Km (mean Km1 = 68 microM) and high-Km (mean Km2 = 7691 microM) components. The low-K(m) enzyme accounted for an average of 96% of estimated intrinsic clearance, and was predicted to contribute more than 50% of net reaction velocity at phenacetin concentrations less than 2000 microM. Among index inhibitor probes, alpha-naphthoflavone was a highly potent inhibitor of the low-Km enzyme (Ki1 = 0.013 microM); furafylline also was a moderately active inhibitor (Ki1 = 4.4 microM), but its inhibiting potency was increased by preincubation with microsomes. Ketoconazole was a relatively weak inhibitor (Ki1 = 32 microM); quinidine and cimetidine showed minimal inhibiting activity. Among six selective serotonin reuptake inhibitor (SSRI) antidepressants, fluvoxamine was a potent inhibitor of 1A2 (mean Ki1 = 0.24 microM). The other SSRIs were more than tenfold less potent. Mean Ki1 values were: fluoxetine, 4.4 microM; norfluoxetine, 15.9 microM; sertraline, 8.8 microM; desmethylsertraline, 9.5 microM; paroxetine, 5.5 microM. The antidepressant nefazodone and four of its metabolites (meta-chloro-phenylpiperazine, two hydroxylated derivatives, and a triazoledione) were very weak inhibitors of P450-1A2. Venlafaxine and its O- and N-desmethyl metabolites showed minimal inhibitory activity.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8986010&dopt=Abstract
kwd match effexor online literature
Br J Pharmacol. 1997 Aug;121(8):1758-62.
Comparison of the effects of sibutramine and other monoamine reuptake inhibitors on food intake in the rat.
Jackson HC, Needham AM, Hutchins LJ, Mazurkiewicz SE, Heal DJ.
Knoll Pharmaceuticals Research & Development, Nottingham.
1. The effects of the potent 5-hydroxytryptamine (5-HT) and noradrenaline reuptake inhibitor (serotonin-noradrenaline reuptake inhibitor, SNRI), sibutramine, on the cumulative food intake of freely-feeding male Sprague-Dawley rats during an 8 h dark period were investigated and compared to those of the selective 5-HT reuptake inhibitor (selective serotonin reuptake inhibitor, SSRI), fluoxetine; the selective noradrenaline reuptake inhibitor, nisoxetine; the 5-HT and noradrenaline reuptake inhibitors, venlafaxine and duloxetine; and the 5-HT releaser and 5-HT reuptake inhibitor, (+)-fenfluramine. 2. Sibutramine (3 and 10 mg kg-1, p.o.) and (+)-fenfluramine (1 and 3 mg kg-1, p.o.) produced a significant, dose-dependent decrease in food intake over the 8 h dark period. These responses became apparent within the first 2 h following drug administration. 3. Fluoxetine (3, 10 and 30 mg kg-1, p.o.), and nisoxetine (3, 10 and 30 mg kg-1, p.o.) had no significant effect on food intake during the 8 h dark period. However, a combination of fluoxetine and nisoxetine (30 mg kg-1, p.o., of each) significantly decreased food intake 2 and 8 h after drug administration. 4. Venlafaxine (100 and 300 mg kg-1, p.o.) and duloxetine (30 mg kg-1, p.o.) also significantly decreased food intake in the 2 and 8 h following drug administration. 5. The results of this study demonstrate that inhibition of 5-HT and noradrenaline reuptake by sibutramine, venlafaxine, duloxetine, or by a combination of fluoxetine and nisoxetine, markedly reduces food intake in freely-feeding rats and suggest that this may be a novel approach for the treatment of obesity.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9283714&dopt=Abstract
kwd match effexor online literature
online pharmacies ||
Hair Million herbal formula for hair loss and hair growth ||
Tramadol ||
Antibiotics and prescription medications online literature ||
Antibiotics