Drugs online research references
Int Clin Psychopharmacol. 1987 Jul;2(3):217-24.
Plasma-serum differences in the assessment of tricyclic antidepressant blood levels.
Coccaro EF, Adan F, Allen D, Cooper TB.
Psychiatry Service, Bronx Veterans Administration Medical Center, NY 10468.
Concomitant plasma and serum tricyclic determinations were performed on 20 patients chronically administered imipramine (N = 10), amitriptyline (N = 10), desipramine (N = 10), and nortriptyline (N = 10). Plasma levels for these tricyclic antidepressants were significantly greater than the corresponding serum levels. Plasma-serum differences for the secondary amines (DMI/NT) were more than twice those for the tertiary amines (IMI/AMI). The authors thus suggest that clinicians and investigators specify the specific source of blood sample when assessing blood levels of the secondary tricyclic antidepressants.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3693867&dopt=Abstract
Acta Pharmacol Toxicol (Copenh). 1985 Jan;56(1):75-80.
Anticholinergic activity in the serum of patients receiving maintenance amitriptyline or doxepin therapy.
Aaltonen L, Syvalahti E, Iisalo E, Peltomaki T.
The anticholinergic activity in serum of depressive patients receiving amitriptyline (50-300 mg/day) or doxepin (50-225 mg/day) was measured using a radioreceptor assay. In this method the membrane suspension prepared from rat brain was able to bind the potent muscarinic antagonist, quinuclidinyl benzilate. Using atropine as a standard, the antimuscarinic activity of several compounds can be measured in the serum of patients receiving drugs with anticholinergic effects or side-effects. The steady state serum levels of amitriptyline and doxepin and their desmethylated metabolites, nortriptyline and desmethyldoxepin were measured by radioimmunoassay in the same serum samples. The antimuscarinic activity in serum measured as atropine equivalents was 2.7 +/- 0.4 (S.E.M.) ng/ml in amitriptyline patients and 1.1 +/- 0.2 ng/ml in doxepin patients. There was a highly significant correlation (P less than 0.001) between amitriptyline (r = 0.92) and nortriptyline (r = 0.79) concentrations and serum antimuscarinic activity. The correlation was less clear, although statistically significant for doxepin (r = 0.42, P less than 0.05) and desmethyldoxepin (r = 0.58, P less than 0.01). The better correlation between serum drug levels and antimuscarinic activity in amitriptyline than in doxepin patients is probably due to the higher affinity of amitriptyline and its desmethylated metabolite to muscarinic receptors with the doses used in the present study. The method may have clinical applications e.g. in evaluation of excessive anticholinergic activity in patients.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3976405&dopt=Abstract
Biol Psychiatry. 1979 Aug;14(4):601-13.
Hydroxylated metabolites of tricyclic antidepressants: preclinical assessment of activity.
Potter WZ, Calil HM, Manian AA, Zavadil AP, Goodwin FK.
Studies investigating a possible relationship between the plasma concentration of tricyclic antidepressants and clinical response have measured only the tertiary and secondary amine forms of these drugs. The present study shows that the hydroxy metabolites of tricyclic antidepressants might also be active. Hydroxylated imipramine, desipramine, chlorimipramine, and nortriptyline inhibit the uptake of norepinephrine and serotonin into synaptosomes to the same extent as do their parent compounds. Hydroxylated nortriptyline and imipramine reverse or prevent reserpine-induced motor retardation and ptosis. Following chronic imipramine, significant steady-state concentrations of unconjugated hydroxylated metabolites are present in rat tissues including the cerebrospinal fluid. Accounting for steady-state concentrations of hydroxylated metabolites of tricyclic antidepressants in man may help to clarify whether there is a relationship between active drug concentration and clinical effect.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=486616&dopt=Abstract
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