Amitriptyline antidepressant

Fi re 4.15 Separation of the tricyclic antidepressant amitriptyline and its major metabolites on a 10 cm x 4.6 mm I. D. column packed with Spherisorb S5H silica with methanol-aqueous ammonium acetate (9 1), pH 9.1, as mobile phase at a flow rate of about 1 ml/min. Peak identification 1 > amitriptyline-N-oxide 2 amitriptyline 3 - E-lO-hydroxyamitriptyline 4 - Z-10-hyroxyamitriptyline 5 desmethylnortrlptyline 6 nortriptyline 7 E-lO-hydroxynortriptyline and 8 - Z-lO-hydroxynortriptyline. (Reproduced with permission from ref. 271. Copyright Elsevier Scientific Publishing Co.)... 

Rao et al.20 demonstrated a fluorescence polarization immunoassay for evaluating serum concentrations of tricyclic antidepressants (amitriptyline, imipramine, clomipramine, and doxepin) with respect to nonresponse, compliance, therapeutic window, and influences of age, sex, substance abuse, and toxicity. Abbott Laboratories TDx/TDxFLx Toxicology Tricyclic Assay FPIA (fluorescence polarization immunoassay) was used. This assay of 50 /uL samples contained tricyclic antidepressant antibodies raised in rabbits and fluorescein-labeled tricyclic antidepressant as a tracer. The assay was calibrated with imipramine in the range of 75 to 1000 fig/L (268 to 3571 nmol/L). Intra-assay and inter-assay coefficients of variation for internal quality control samples from the manufacturer were 4.2 and 4.7%, respectively. The limits of detection were 72,71,64, and 72 nmol/L for amitriptyline, imipramine, clomipramine, and doxepin, respectively. This high-throughput immunoassay was easy to use although amitriptyline, dosulepine, desipramine, and nortriptyline showed cross-reactivities ranging from 74 to 100%. 

Antidepressants amitriptyline, clomipramine, imipramine, moclobemide, citalopram Antipsychotics olanzapine... 

Diazepam, oxazepam, and N-desmethyldiazepam have been determined under isocratic conditions (342) a somewhat more sensitive assay for diazepam and N-methyldiazepam has been reported (545). The closely related compounds, chlordiazepoxide and its N-demethyl metabolite, have also been determined (344). Analysis of the antidepressant amitriptyline, its metabolites and related drugs have been carried out using a four-component solvent (345, 346) and also aqueous acetonitrile (547). 

Tricyclic antidepressants Amitriptyline Clomipramine Desipramine Doxepin Imipramine Trimipramine... 

Reul JMHM, Stec I, Soder M, et al Chronic treatment of rats with the antidepressant amitriptyline attenuates the activity of the hypothalamic-pituitary-adrenocortical system. Endocrinology 133 312-320, 1993... 

Figure 1.15 The Butterfly Angle . Tricyclic drugs consist of anticonvulsants (carbamazepine), antidepressants (amitriptyline), and antipsychotics (chlorpromazine). Although aU three families consist of three interconnected ring systems, the orientation between the rings varies, imparting a different spectrum of bioactivity.

One-third of the patients in each of the two groups were then given an antidepressant (amitriptyline) in doses of 100 200 mg per day, one-third were given placebo and the remaining one-third received no tablets at all. 

TABLE 7-2. Polypharmacy with a single drug cocktail" of effects of the tricyclic antidepressant amitriptyline... 

Some naturally occurring neurotransmitters may be similar to drugs we use. For example, it is well known that the brain makes its own morphine (i.e., beta endorphin), and its own marijuana (i.e., anandamide). The brain may even make its own antidepressants, it own anxiolytics, and its own hallucinogens. Drugs often mimic the brain s natural neurotransmitters. Often, drugs are discovered prior to the natural neurotransmitter. Thus, we knew about morphine before the discovery of beta-endorphin marijuana before the discovery of cannabinoid receptors and anandamide the benzodiazepines diazepam (Valium) and alprazolam (Xanax) before the discovery of benzodiazepine receptors and the antidepressants amitriptyline (Elavil) and fluoxetine (Prozac) before the discovery of the serotonin transporter site. This un-... 

Berger and Wilson also reported the separation of 10 antidepressants (amitriptyline, imipramine, nortriptyline, desipramine, protripyline, bucliz-ine, benactyzine, hydroxyzine, perphenazine, and thioridazine) using a packed-column SFC with a tertiary mobile phase [37], A Lichrosphere cyanopropyl column with a mobile phase consisting of supercritical fluid carbon dioxide with 10% modifier (methanol with 0.5% isopropylamine) was used for the separation. It was noted that solutes did not elute without the addition of isopropylamine. Detection limits obtained were as low as 88 ppb for a 5-jul injection. 

Spherisorb propyl SCX (3 pm) Spherisorb phenyl SCX (3 pm) Symmetry SCX (3 pm) Spherisrob Mixed Mode (3 pm) Evaluation of various SCX phases, compariosn of electroosomotic mobility at various pHs, separation of antidepressants, amitriptyline, nortriptyline, neutral test mixture MeCN-50 mM phosphate 70 30, pH 2.3 MeCN-20 mM borate 70 30, pH 9.0 [97]... 

Treatment with antidepressants will affect a person s ability to drive or operate machinery. Among the tricyclic antidepressants, amitriptyline and doxepin impair skills compared with imipramine and nortriptyline. Fluoxetine and dothiepin also show similar effects, such as affecting ability to work. The United Kingdom s Medical Commission on Accident Prevention has recommended that patients on long-term psychotropic medication are unsuitable drivers of heavy vehicles or public transport services.132,133... 

Therefore some advertisements emphasised the sedative action of tricyclic antidepressants. Amitriptyline, for example, was frequently recommended for its sedative action. It was described in one advert as having intrinsic tranquillising properties and additional sedative action which relieves insomnia, agitation and anxiety (Tryptizol advertisement 1964). Drinamyl, the combination of amphetamine and a barbiturate... 

Spurred on by Laughren s (1991) critique, an exchange of memos occurred between Paul Leber and his boss, Robert Temple, Director, Office of Drug Evaluation 1. The continuing subject was the approval of Zoloft, whose efficacy as an antidepressant remained in doubt up to the last minute. Temple noted that Zoloft was not being approved in some European countries because of its lack of robustness in the efficacy trials. Zoloft often failed to do any better than placebo in studies in the United States and never did as well as the older antidepressant amitriptyline. Despite these pervasive failures, one positive study and two supportive studies were found sufficient to earn approval. 

In a systematic review of 32 randomized trials in which 1389 patients took lithium and 2069 took another agent (carbamazepine, divalproex, lamotrigine, or the antidepressants amitriptyline, fluvoxamine, mianserin, and maprotiline), among the seven studies that reported suicides, lithium-treated patients had significantly fewer completed events (242). These included two suicides on lithium (out of 503, 0.4%) and 11 suicides on other agents (two placebo, two amitriptyline, six carbamazepine, and one lamotrigine, out of a total of 601,1.8%) (OR = 0.26 95% Cl = 0.09, 0.77). 

If, following absorption, medications were undisturbed by the body, we would need to take only one dose for an eternal effect. Of course, this is not the case. As soon as drugs enter the bloodstream, the process of metabolism ensues. The body recognizes the drug as a foreign substance and eliminates it outright (say, via the kidneys, as in the case of lithium) or transforms it chemically, using a complex enzyme mechanism located in the liver. This chemical transformation enables the medication to be eliminated from the body. In some cases, the chemical transformation produces a new compound that may also have therapeutic effects (or, in some rare instances, a toxic effect). For example, fluoxetine (trade name Prozac) is transformed into norfluoxetine, which is also an antidepressant. A similar situation occurs with the old tricyclic antidepressants (amitriptyline—trade name Elavil—to nortriptyline the latter, in fact, is... 

SUCRALFATE ANTIDEPRESSANTS -AMITRIPTYLINE Possible l amitriptyline levels 1 absorption of amitriptyline Watch for poor response to amitriptyline... 

Tricyclic antidepressants (amitriptyline, ST segment elevation Altered ion homeostasis... 

CYP1A2 Antidepressants amitriptyline, clomipramine, imipramine, fluvoxamine Neuroleptics haloperidol, phenothiazines, thiothixene, clozapine, olanzapine Others tacrine, caffeine, theophylline, acetaminophen, phenacetin No report of polymorphism until 1999 significance of following findings remains unclear 1C reduced activity 23% in Japanese 1F higher inducibility 32% in Caucasians... 

---