Drugs online research references
Pharmakopsychiatr Neuropsychopharmakol. 1976 Jan;9(1):18-26.
Treatment of depression with tricyclic drugs--pharmacokinetic and pharmacodynamic aspects.
Asberg M.
A series of studies on the pharmacokinetic and pharmacodynamic properties of some tricyclic antidepressants is reviewed. During treatment with the same oral dose of these drugs, patients develop widely differing plasma levels. The importance of this variability for the clinical effects has been studied in detail for the monomethylated compound, nortriptyline. There is an association between side-effects and high plasma levels of this drug. In endogenously depressed patients, the relationship between plasma level and effect appears to be curvilinear. The tricyclic antidepressants differ in their capacity to inhibit transmitter uptake into noradrenaline- and serotonin neurons respectively. Nortriptyline is a preferential noradrenaline uptake inhibitor, while the dimethylated compound, chlorimipramine also has a profound influence on serotonin neurons. These differential effects are also reflected in changes in the levels of the transmitter metabolites in cerebrospinal fluid (CSF). The CSF studies have also supported the hypothesis of a biochemical heterogeneity of the depressive syndrome. The levels of the serotonin metabolite, 5-HIAA were bimodally distributed in CSF. In patients with a low level of 5-HIAA there was a significant correlation between the CSF metabolite level and the severity of the depression, and these patients also appeared to be more suicide-prone than those with higher 5-HIAA levels. These patients seemed to be less amenable to treatment with nortriptyline. The effect of chlorimipramine treatment in this subgroup of depressives is presently being explored.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10583&dopt=Abstract
uni-tuebingen.de
Aldo-keto reductases (AKR) form an enzyme superfamily catalyzing the reduction of carbonyl compounds and in some cases the reverse oxidation of alcohols as well. In particular, a role in drug metabolism has been considered for the AKR1C family, but published data failed to reveal low Km drug substrates. Moreover, structure activity relationships using chemically related substrates have not been established. In the present investigation, a modified procedure was developed for the isolation of AKR1C1, 1C2, and 1C4 (dihydrodiol dehydrogenases 1, 2, and 4) from human liver cytosol along with carbonyl reductase (EC 1.1.1.184), a member of the short-chain alcohol dehydrogenase superfamily. The kinetics of NADPH-dependent reduction by the closely related enzymes AKR1C1 and 1C2 were studied with the structurally similar substrates (R)- and (S)-ketotifen and E- and Z-10-oxonortriptyline by HPLC measurement of the products. Km values varied between 2.6 and 53 microM and Vmax values between 5 and 313 mU/mg protein; substrate inhibition with Ki around 30 microM occurred in the reduction of E- and Z-10-oxonortriptyline by AKR1C1. The reactions were strictly stereospecific with production of one enantiomeric alcohol from each ketotifen enantiomer and of the (+)-enantiomers of E- and Z-10-hydroxynortriptyline. Enzymatic NADP+ -dependent oxidation of the alcohols mirrored the reduction with regard to stereochemical specificity. All four ketones were no or poor substrates of carbonyl reductase, whereas haloperidol was reduced by this enzyme with low affinity, but high efficiency.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10609553&dopt=Abstract
Analyst. 1999 May;124(5):759-62.
Analysis of tricyclic antidepressants using electrogenerated chemiluminescence.
Greenway GM, Dolman SJ.
School of Chemistry, University of Hull, UK.
A novel method has been investigated for the selective and sensitive determination of a range of tricyclic antidepressants including amitriptyline, doxepin, nortriptyline, promazine, chlorpromazine, imipramine, clomipramine, desipramine, protriptyline and trimipramine using electrogenerated chemiluminescence (ECL). The ECL mechanism is based on the reaction between tris(2,2'-bipyridyl)ruthenium(II) [Ru(bpy)3(2+)] and the tertiary amino groups on the antidepressants. After selecting the best operating parameters calibration curves were obtained over three orders of magnitude for amitriptyline, doxepin, nortriptyline, promazine and chlorpromazine. Linear calibrations were used to obtain limits of detection in the range 0.09-0.24 microgram ml-1 with relative standard deviations below 4% for five replicate samples. Rapid depression in the signal was observed with repeat analysis of imipramine, clomipramine, protriptyline, desipramine and trimipramine due to electrode fouling by the oxidation product of the reaction. Use of a lower concentration of the compound was found to alleviate the problem. Finally the concentration of doxepin was determined in a pharmaceutical preparation.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10616739&dopt=Abstract
Herbs and Pharmaceuticals Online ||
Hair Million herbal formula for hair loss and hair growth ||
Wellstreet online pharmacy for click-order prescription medications ||
Altace Online Pharmacy ||
Rx Drugs USA, Prescription Drugs Online Pharmacy ||
Insurance plans and information ||
Insurance policies for all purposes ||
Antibiotics and prescription medications online literature ||