Automated determination of drugs in serum by column-switching high-performance liquid chromatography. IV. Separation of tricyclic and tetracyclic antidepressants and their metabolites.
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We describe automated column-switching high-performance liquid chromatography for determining nine tricyclic and tetracyclic antidepressants (TCAs) and their metabolites in human serum. TSKgel ODS-80TM and TSKprecolumn PW (Tosoh Co., Tokyo) are used in the analytical column and the precolumn, respectively. A 200-microL serum sample is directly injected onto the precolumn. After washing the serum proteins from the precolumn with potassium phosphate buffer, the precolumn connection is switched to introduce the retained substances onto the analytical column. The drugs are then eluted within 30 min with an acetonitrile/potassium phosphate buffer mixture containing sodium 1-heptanesulfonate. The analytical recoveries (95-104%), reproducibilities (within-run CV less than 3%), and detection limits (10 micrograms/L) indicate that this HPLC system is suited for therapeutic drug monitoring. Correlations were good between the TCA concentrations in serum and administered dose (r = 0.713, n = 41), and between 10-hydroxynortriptyline and nortriptyline in serum (r = 0.691, n = 24). (+info)
Inhibitory actions of amoxapine, a tricyclic antidepressant agent, on electrophysiological properties of mammalian isolated cardiac preparations.
(10/14)
1. The electrophysiological effects of amoxapine were examined in guinea-pig isolated papillary muscles and rabbit sinoatrial nodes using a conventional microelectrode technique. 2. In papillary muscles, amoxapine above 10 microM caused a dose-dependent decrease in the maximum upstroke velocity (Vmax) of the action potential and in the action potential amplitude (APA), whereas the action potential duration at 90% repolarization (APD90) was significantly prolonged. For a decrease in Vmax, amoxapine produced a negative shift of the curve relating Vmax to the resting potential (Em) along the voltage axis to more negative membrane potentials. 3. Amoxapine also decreased Vmax and the overshoot potential of K+-depolarized slow action potentials of papillary muscle preparations. 4. In spontaneously beating sinoatrial node preparations, amoxapine above 3 microM reduced the heart rate, Vmax, APA and the slope of phase 4 depolarization in a dose-dependent manner. 5. It was concluded that amoxapine exerts inhibitory actions on fast- and slow-response fibres of the heart and these actions can be mainly explained by inhibition of both fast Na+ and slow Ca2+ channels. (+info)
Electrophysiological effects of amoxapine in untreated and in amoxapine-pretreated rat atria.
(11/14)
The effects of amoxapine (10(-7)-10(-4) M) have been studied in rat atrial fibres obtained from untreated animals and animals pretreated for 28 days with amoxapine (10 mg kg-1, i.p.). In untreated atria amoxapine reduced atrial rate, contractile force and df/dtmax, prolonged the sinus node recovery time and decreased atrial excitability. Amoxapine also decreased amplitude and Vmax of the upstroke, prolonged the duration of the action potential (APD) and effective refractory period (ERP) and reduced the resting membrane potential. During the treatment with amoxapine behavioural and cardiovascular adverse effects, including hypotension, tachycardia and prolongation of the Q-Tc, were observed. However, with the exception of the ERP which was significantly prolonged in pretreated atria, pretreatment with amoxapine did not modify the control values of the measured parameters compared to those obtained in untreated atria. Further addition of amoxapine produced similar changes in both pretreated and untreated atria. However, in contrast to untreated atria, in pretreated atria the prolongation of the ERP produced by amoxapine exceeded the prolongation of the APD and thus, the ERP/APD ratio increased. The decrease in atrial excitability was also more marked in pretreated than in untreated atria. Amoxapine inhibited the slow action potentials and contractions induced by isoprenaline in K-depolarized atria. It is concluded that the electrophysiological effects of amoxapine on rat atrial fibres are similar to those described for other tricyclic antidepressants. Possible explanations for the lower cardiodepressant activity of amoxapine are discussed. (+info)
Determination of the antidepressants maprotiline and amoxapine, and their metabolites, in plasma by liquid chromatography.
(12/14)
Maprotiline, amoxapine, and their metabolites were determined in plasma by three separate procedures, each of which involves a three-step extraction followed by reversed-phase separations. Amoxapine, maprotiline, and N-desmethylmaprotiline can be measured with use of a conventional C-18 column with 10% carbon load, but analyses for 7- and 8-hydroxyamoxapines require a small (5-microns) particle size, high carbon load, 20% C-18 column with 0.2 mol/L phosphate as mobile phase. Within-run and day-to-day CVs were 5% and 8%, respectively. Peak-height ratios were linearly correlated with concentrations between 0 and 400 micrograms/L. Detection limits ranged from 1 to 3 ng. Interference studies indicated that nortriptyline co-elutes with maprotiline. Assays of patients' plasma showed substantial amounts of these drugs and most of their metabolites, but only trace amounts of 7-hydroxyamoxapine. (+info)
Liquid-chromatographic determination of amoxapine and 8-hydroxyamoxapine in human serum.
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We describe a liquid-chromatographic procedure for amoxapine and 8-hydroxyamoxapine, its active metabolite, in serum. We used a mu-Bondapak C18 reversed-phase column and a mobile phase of acetonitrile/water (74/26 by vol) plus 26 microL of n-butylamine per liter. The compounds were measured at 254 nm, with 8-methoxyloxapine as internal standard. Necessary pre-analysis purification consisted of adsorbing the drug from serum onto extraction columns, eluting with 1-butanol/hexane (1/5 by vol), re-extracting into aqueous acid, and from that re-extracting again into the elution-solvent mixture. We prefer this procedure for monitoring both therapeutic and toxic concentrations of amoxapine, because parent drug and metabolite are measured separately. (+info)
The efficacy of antidepressants in post-stroke depression.
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The aim of the present study was to confirm the efficacy of antidepressants in post-stroke depression and to identify the factors related to outcome. Subjects consisted of 20 inpatients suffering from post-stroke in a rehabilitation hospital. The subjects were treated with various antidepressants, mainly imipramine, amitriptyline, and amoxapine. After 4 weeks of treatment, 13 showed some improvement; significant improvement in 5, moderate improvement in 5, mild improvement in 3 by a clinical global impression. Whereas all the patients aged less than 65 yr were responders, only 3 of the 10 patients over 65 yr were responders. All of the male patients, but only half of the female patients, were responders. With regards to the presence of a spouse, 13 of the 16 patients with a spouse, but none of 4 patients without, showed a response. No significant correlation was found between the occurrence of each depressive symptom and outcome. Thus, the responders were younger and had better social support in comparison with the non-responders. This result implies that antidepressants are effective for post-stroke depression. (+info)