Drugs online research references
Clin Pharmacol Ther. 1987 Jul;42(1):10-9.
Clinical and biochemical effects during treatment of depression with nortriptyline: the role of 10-hydroxynortriptyline.
Nordin C, Bertilsson L, Siwers B.
Plasma concentrations of nortriptyline (NT) and its major metabolite 10-hydroxy-NT (10-OH-NT) were measured in 30 patients with depression, treated with NT for 3 weeks. Nine patients who recovered completely had plasma concentrations of NT and 10-OH-NT ranging from 358 to 728 nmol/L and from 428 to 688 nmol/L, respectively. Of the 21 patients who did not recover completely, only four had plasma concentrations within the window limited by these two plasma concentration ranges. A correlation was found between the degree of amelioration and the plasma concentration of NT (rs = 0.469; P less than 0.01). Lumbar punctures were performed in 26 patients before and after 3 weeks of NT treatment. During treatment there was a 30.9% mean decrease in the noradrenaline metabolite 4-hydroxy-3-methoxyphenylglycol (HMPG) in cerebrospinal fluid (CSF). We could not evaluate the extent to which this decrease was caused by NT or 10-OH-NT, respectively, because both are strong inhibitors of noradrenaline uptake. The ratio between the concentration of NT and 10-OH-NT in CSF correlated to the reduction of HMPG in CSF (r = 0.397; P less than 0.05) and to the amelioration of depression (rs = 0.623; P less than 0.001). This might indicate that NT and 10-OH-NT interact on the noradrenaline system in a nonadditive way. During treatment there was a 15.2% decrease in CSF concentration of the serotonin metabolite 5-hydroxyindoleacetic acid. The reduction was significantly correlated to the CSF concentration of NT but not to that of 10-OH-NT. This is in accordance with the fact that NT is a more potent inhibitor of serotonin uptake than is 10-OH-NT. The dopamine metabolite homovanillic acid in CSF decreased significantly by 10.0%. The biochemical data indicate that noradrenergic, serotoninergic, and dopaminergic systems are affected by NT treatment and that 10-OH-NT might be more selective on noradrenergic neurons than the parent drug.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2439250&dopt=Abstract
Neuropsychobiology. 1987;17(3):139-44.
Comparative study of the effects of 9 antidepressants on several physiological parameters in healthy volunteers.
Ogura C, Kishimoto A, Mizukawa R, Matsubayashi M, Omura F, Kunimoto N.
Department of Neuropsychiatry, School of Medicine, University of the Ryukyus, Okinawa, Japan.
Effects on physiological parameters were compared among 9 antidepressants (amitriptyline 50 mg, imipramine 50 mg, nortriptyline 50 mg, amoxapine 50 mg, maprotiline 50 mg, mianserin 20 mg, zimelidine 100 mg, nomifensine 50 mg, and Y-8894 50 mg) after a single oral administration in healthy volunteers. Critical fusion frequency of flicker, body sway distance, salivary flow rate, near blurred point, and pulse rate were employed as parameters. The degree of the drug effects on the physiological parameters could be roughly classified into two to four groups according to maximum percent deviation of each parameter.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3683803&dopt=Abstract
JAMA. 1977 Nov 14;238(20):2167-9.
Tricyclic plasma levels. Effect of age, race, sex, and smoking.
Ziegler VE, Biggs JT.
Steady-state plasma tricyclic antidepressant levels were determined in 65 patients undergoing treatment for depression with either amitriptyline hydrochloride or nortriptyline hydrochloride to determine if common factors such as age, race, sex, or smoking status were predictors of steady-state drug levels that have been shown to vary up to 36-fold. Evaluation of these factors did not disclose differences in the rate of demethylation of amitriptyline to nortriptyline, or steady-state tricyclic levels in the amitriptyline-treated patients. No differences were found in the nortriptyline-treated patients except regarding race. Black patients had significantly higher (50%) nortriptyline plasma levels than did white patients, which may explain the more rapid response to tricyclic treatment demonstrated in blacks. Decreased rates of nortriptyline metabolism in blacks can result in increased side effects and treatment failure if the therapeutic plasma range is exceeded.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=578829&dopt=Abstract
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