Drugs online research references
med-rz.uni-sb.de
A procedure is presented for determination of the catechol-O-methyltransferase (COMT) activity in liver cytosolic preparations using 3,4-dihydroxyphenethylamine as substrate and by quantifying the product 3-methoxy-4-hydroxyphenethylamine (3-MHP). For quantification of 3-MHP in liver cytosolic preparations a gas chromatographic-mass spectrometric procedure after liquid-liquid extraction and acetylation was established and validated. The intra- and inter-day accuracy and precision were better than 15% and 20%, respectively. Extraction efficiency and selectivity were also sufficient. For in statu nascendi derivatization of unstable catecholic metabolites in liver microsome preparations, cytosolic preparations with COMT activities of at least 1 nmol product/min/mg protein were used after addition of S-adenosylmethionine. Such catecholic metabolites, which are claimed to be responsible for toxic effects in vivo, e.g., neurotoxicity or carcinogenesis, must not be overlooked in in vitro metabolism studies. Using this trick, gas chromatography-mass spectrometry (GC-MS) was suitable for the determination of catecholic metabolites in human and rat liver preparations after the same sample preparation as for 3-MHP quantification. The applicability was exemplified for the antidepressant paroxetine.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10755376&dopt=Abstract
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Pharmacol Biochem Behav. 2000 Apr;65(4):591-7.
Effect of subchronic antidepressant treatments on behavioral, neurochemical, and endocrine changes in the forced-swim test.
Connor TJ, Kelliher P, Shen Y, Harkin A, Kelly JP, Leonard BE.
Department of Pharmacology, National University of Ireland, Galway, Ireland.
The purpose of the present study was to examine the effect of subchronic treatment (24 days) with antidepressants displaying differential effects on noradrenaline and serotonin reuptake, on behavior, neurochemistry, and hypothalamic-pituitary-adrenal (HPA) axis activity following FST exposure in the rat. Desipramine (7.5 mg/kg, IP) significantly decreased immobility in the FST, whilst paroxetine (7.5 mg/kg IP) and venlafaxine (10 mg/kg, IP) were without effect. Nonetheless, treatment with all three antidepressants significantly attenuated stress-related increases in amygdaloid and cortical serotonin turnover. Of the three antidepressants examined, only desipramine attenuated the stress-associated elevation in serum corticosterone. In conclusion, although FST-induced increases in serotonin turnover in the frontal cortex and amygdala were attenuated following treatment with all three antidepressants, FST-induced behavioral changes and increased HPA axis activity were normalized only following desipramine treatment. In addition, these results suggest that neurochemical mechanisms independent of increased serotonergic activity subserve the normalization of behavior and HPA axis responses in the FST. These data also add to our understanding of the interactions between antidepressants and stress-induced behavioral, neurochemical, and endocrine alterations, and illustrates important differences between classes of antidepressants.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10764911&dopt=Abstract
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Med Interface. 1995 Aug;8(8):114-9, 123.
Antidepressant utilization in managed care: an evaluation of SSRI use in two HMO settings.
Navarro R, Valler WE, Spangler M.
Emron, Inc., Warren, NJ 07059, USA.
Antidepressant costs and utilization are growing rapidly as newer selective serotonin reuptake inhibitors (SSRIs) comprise an ever-increasing share of the market. A number of factors and related costs must be considered when evaluating antidepressant products. An antidepressant drug utilization review study performed in two different HMO models revealed important variations among available SSRI therapies in terms of dosage escalation and discontinuation, as well as concomitant medication costs associated with treating side effects. New antidepressants may alleviate some of these problems.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10144769&dopt=Abstract
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