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PubMed2005

Application of two chemometric methods for the determination of imipramine, amitriptyline and perphenazine in content uniformity and drug dissolution studies.

Double-divisor spectra derivative and partial least squares methods were developed for content uniformity and dissolution tests in binary or ternary mixtures. The simultaneous determinations of perphenazine (PER) combined with amitriptyline hydrochloride (AMI) and/or imipramine hydrochloride (IMI) have been accomplished using the information of the absorption spectra of appropriate solutions. The double-divisor method is based on the use of the first derivative of the ratio spectrum obtained by dividing the absorption spectrum of the ternary mixture PER-AMI-IMI by a standard spectrum resulted from the addition of two of the three analytes in equal concentrations. The concentration of each component is then determined from their respective calibration graphs established by measuring the ratio derivative analytical signal at a specific wavelength. In this method, the linear determination ranges were of 3.65-18.24 microg/mL for PER, 4.32-21.60 microg/mL for AMI, and 4.83-24.19 microg/mL for IMI. The results were compared with those obtained by partial least squares multivariate calibration (PLS) method pre-treated by a wavelet compression-orthogonal signal correction (W-OSC) filter in zero-order derivative spectra. The calibration model was evaluated by internal validation (cross-validation) and by external validation over synthetic mixtures, content uniformity and dissolution tests. According to the dissolution profile test more than 95% of the three substances were dissolved within 10 min. The results from both techniques were statistically compared with each other and can be satisfactorily used for quantitative analysis and dissolution tests of multicomponent tablets.

Amitriptyline↗
PubMed2004

Modulation of neuronal glutamate transporter rEAAC1 mRNA expression in rat brain by amitriptyline.

Glutamate transporters regulate the glutamate concentration in the synaptic cleft within the CNS, a regulation required for normal brain function. In several neurological conditions, the amount of glutamate is altered. One reason for the changes in glutamate concentration might be impaired glutamate transporter function. In this study, an in situ hybridisation technique has been used to elucidate changes in mRNA expression of the glutamate transporter, excitatory amino acid carrier 1 (EAAC1), after treatment with the tricyclic antidepressant (TCA) amitriptyline. The results lead to the suggestion that treatment with tricyclic antidepressants leads to changes in the EAAC1 mRNA expression in rat brain suggesting involvement of the glutamate system in the tricyclic treatment of depression.

Amino Acid Transport System X-AG↗
PubMed2006

Spectrophotometric determination of trazodone, amineptine and amitriptyline hydrochlorides through ion-pair formation using methyl orange and bromocresol green reagents.

A simple and rapid extraction spectrophotometric procedure has been developed for the determination of tricyclic anti-depressant drugs such as trazodone (TZH), amineptine (APH) and amitriptyline (ATPH) hydrochlorides in pure form and in different dosage forms. The method involves the formation of intense yellow ion-pairs between these drugs under investigation and methyl orange (MO) and bromocresol green (BCG) reagents followed by their extraction with 1,2-dichloroethane and quantitative microdetermination at 420 and 410 nm using MO or BCG, respectively. The optimum experimental conditions for the ion-pairs formation are established. The method permits the determination of TZH, APH and ATPH over a concentration range of 2-50, 2-50 and 1-25 microg ml(-1) for TZH, APH and ATPH, using MO and 1-25 microg ml(-1) for TZH, APH and ATPH, using BCG, respectively. The Sandell sensitivity (S) is found to be 0.106, 0.1071 and 0.0907 g cm(-2) for TZH, APH and ATPH, respectively, using MO reagent and 0.0788, 0.0661 and 0.0494 g cm(-2) for TZH, APH and ATPH, respectively, using BCG. The method is applicable for the assay of the investigated drugs in different dosage forms and the results are in good agreement with those obtained by the official method.

Amitriptyline↗
PubMed2006

Spectrophotometric determination of trazodone, amineptine and amitriptyline hydrochlorides through ion-pair formation with molybdenum and thiocyanate.

Extraction spectrophotometric method has been developed for the determination of tricyclic drugs such as trazodone (TZH), amineptine (APH) and amitriptyline (ATPH) hydrochlorides in pure form and in the dosage forms coming from different Egyptian markets. The method based on the formation of ion-pairs between these drugs under investigation and inorganic complex of Mo(V)-thiocyanate followed by its extraction with methylene chloride. The optimum conditions for the ion-pairs formation are established. The method permits the determination of TZH, APH and ATPH over the concentration range of 2-28, 2-32 and 1-30 microg ml(-1), respectively. The Sandell sensitivity (S) is found to be 0.105, 0.138 and 0.118 g cm(-2) for TZH, APH and ATPH, respectively. The SD is found to be 0.16-0.377, 0.12-0.259 and 0.091-0.286 and the R.S.D. are 0.14-0.55, 0.12-0.399 and 0.095-0.485 for TZH, APH and ATPH, respectively. The method is applicable for the assay of the investigated drugs in different dosage forms and the results are in good agreement with those obtained by the official method.

Absorption↗
PubMed1998

Effect of chronic amitriptyline administration on serotonergic receptors in rats with methylazoxymethanol-induced microencephaly.

Methylazoxymethanol (MAM)-induced cortical hypoplasia resulted in a 20% decrease in the Bmax of 5-HT2A receptors in the frontal cortex with no change in the Bmax of 5-HT1A receptors. Chronic treatment with amitriptyline did not further decrease the Bmax of 5-HT2A receptors in the MAM-lesioned cortex, suggesting that the persistent down-regulation of cortical 5-HT2A receptors in MAM-lesioned rats was induced by serotonergic hyperinnervation.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1981

Two-phase derivatization of amitriptyline and structurally related tertiary amines for gas chromatography with electron-capture detection.

A new derivatization technique for tertiary amines has been developed. The amine is extracted at ambient temperature after addition of sodium iodide with methylene chloride containing an aryl chloroformate ester. By use of two new reagents, 2,4-dichlorophenyl and pentafluorophenyl chloroformate, the carbamates formed have high electron-capture response. The derivatization is rapid, often completed within 5 min. Amitriptyline was determined down to 6 ng/ml directly in a spiked plasma sample. A method for selective derivatization of a tertiary amine in the presence of the corresponding secondary amine is given.

Amitriptyline↗
PubMed1997

Dimeric tubulin-stimulated adenylyl cyclase activity is augmented after long-term amitriptyline treatment.

We have investigated altered association of tubulin dimers interacting with G proteins and modulating adenylyl cyclase (AC) as a result of long-term amitriptyline (AMT) treatment. Gpp(NH)p-stimulated, but not basal or manganese-stimulated, AC activity was significantly augmented in cortex membranes prepared from rats chronically treated with AMT. The enhancement of AC activity by Gpp(NH)p-liganded tubulin (tubulin-Gpp(NH)p) was significantly higher in chronically AMT-treated rats than in control rats. Moreover, in cortex membranes from controls, tubulin-Gpp(NH)p prepared from chronically AMT-treated rats was more effective to activate AC activity than tubulin-Gpp(NH)p from controls. Immunoblotting and photoaffinity guanine nucleotide binding procedures showed no significant differences in the amount and the function of G proteins between controls and AMT-treated groups. It is suggested that long-term AMT treatment causes alteration in the functional interaction between tubulin and G protein, and this modification may participate in enhanced coupling of Gs to the catalytic subunit of AC induced by the chronic antidepressant treatment.

Adenylyl Cyclases↗
PubMed1998

The use of amitriptyline in patients with urinary frequency and pain.

OBJECTIVE: To evaluate the usefulness of amitriptyline (AMI) in the treatment of patients with urinary frequency or genital, pelvic, or suprapubic pain syndromes. METHODS: Charts of 22 patients (12 male and 10 female) without interstitial cystitis and having vague nonspecific urinary and pelvic or genital complaints were reviewed. All were treated with AMI in doses ranging from 25 to 100 mg. RESULTS: Eleven patients became symptom-free, six showed significant improvement and five did not respond. Four of the five could not tolerate the medication. Fifteen patients attempted tapering off the medication after 6 months, and 11 experienced an early return of symptoms. A therapeutic response was again seen with retreatment. CONCLUSIONS: AMI is therapeutically useful in vague voiding dysfunctions, especially in the presence of urinary frequency or genital, pelvic, or suprapubic pain. It is effective for the treatment of both men and women. The response is durable, but the dose of the medication must be maintained.

Adult↗
PubMed1998

Repeated sleep deprivation once versus twice a week in combination with amitriptyline.

OBJECTIVE: Although a combination of antidepressive pharmacotherapy with repeated sleep deprivation therapy has proved to be an effective and easily applied treatment strategy, no systematic study investigating the most favourable interval between the sleep deprivation trials is available. METHOD: In a cross-over design, 44 patients with a major depressive episode (ICD-10) were randomly allocated to 4 weeks treatment with amitriptyline (150 mg/d) in combination with either late sleep deprivation (of the second half of the night, LSD) twice weekly during week 1 and 2 followed by LSDs once weekly during week 3 and 4 or vice versa. Two hypotheses were tested: Does LSD twice weekly during week 1 and 2 accelerate the clinical response compared with LSD once weekly? Does LSD twice weekly during week 3 and 4 improve the response rate compared with LSD once weekly? RESULTS: According to both observer rating (Hamilton Rating for Depression, 21-item version) and self-rating (Visual Analogue Mood Scale), no significant differences could be ascertained between the groups compared at any time of the investigation. With respect to drop-outs and immediate LSD effects there is a trend for patients undergoing twice weekly LSDs followed by once weekly LSD trials to have a more favourable treatment course than the control group. CONCLUSION: The hypotheses tested were answered in the negative. "High dose" LSD administration does not prove to be clearly superior to "low dose" LSD. This finding is in line with most of the corresponding data on antidepressive pharmacotherapy.

Adult↗
PubMed1998

Chronic amitriptyline treatment induces hippocampal NGFI-A, glucocorticoid receptor and mineralocorticoid receptor mRNA expression in rats.

Adult male rats were treated with the antidepressant drug amitriptyline for 21 days and the expression of specific transcription factors was examined. NGFI-A mRNA expression was increased in the hippocampus and in the cerebral cortex. MR mRNA was increased in the hippocampus while GR mRNA was increased in selective hippocampal regions. There was no change in the NGFI-B mRNA expression. Thus, NGFI-A may be a mediator of plasticity-related phenomena induced by antidepressant drugs.

Amitriptyline↗
PubMed2001

The antidotal effect of alpha(1)-acid glycoprotein on amitriptyline toxicity in cardiac myocytes.

Tricyclic antidepressants in overdose cause toxicity marked by prolongation of the QRS interval of the electrocardiogram. These drugs are bound to alpha(1)-acid glycoprotein (AAG) with high affinity in plasma. Animal studies have shown that the administration of AAG shortens the QRS prolongation induced by tricyclic antidepressants. In order to clarify the pharmacological mechanism involved and to obtain clinically relevant evidence at the cellular level, whole-cell patch clamp techniques were performed in single guinea-pig ventricular myocytes to elicit the time and voltage-dependent fast sodium currents using both normal and modified physiological solutions. Cells stayed viable for much longer when they were placed in normal physiological solutions, providing sufficient recording time for consistently reproducible, clinically relevant toxicological results to be obtained. Amitriptyline (AMI) produced a concentration-dependent blockade of sodium currents with an approximate IC(50) of 0.69 microM. AAG reversed this blockade in a concentration-dependent fashion at concentrations ranging from 3.2 to 12.8 microM. Using the same experimental conditions, AAG also reversed the blockade of sodium current by quinidine, a class I antiarrythmic drug. Albumin did not reverse the blockade of sodium channels by AMI. The results indicate that AAG is a potential antidote for tricyclic antidepressant overdose.

Algorithms↗
PubMedDate not supplied

[Activation with amitriptyline: electroclinical comments on 120 epileptic patients (author transl's)].

The sleep-inducing and epileptogenic effects of amitripyline (0.5 mg/kg i.m.) were studied in 120 epileptic patients. Sleep occurred in 94 p. 100 of the patients: 92 p. 100 showed stages I and II, 42 p. 100 also showed stages III and IV, but only 12 p. 100 showed REM. Major activation of inter-ictal abnormalities occurred in 41 p. 100 and seizures were provoked in 17 patients (14 p. 100). Neutral results were obtained in 23 p. 100 of cases. The results obtained and the complete absence of drawbacks recommend amitriptyline for use in studying epileptic patients, at least before turning to other pharmacological techniques which are more dangerous and probably less reliable.

Adolescent↗
PubMed1987

[Changes in slow evoked potentials in depressed patients treated with amitriptyline and oxaprotiline].

Using a simple S1S2-R paradigm, acoustically evoked potentials, CNV, and PINV were recorded in 59 patients with major depressive disorder before and during a 4 week double blind pharmacological treatment with either amitriptyline (AT) or oxaprotiline (OT). In parallel, 30 healthy subjects were investigated 3 times, in identical intervals of 2 weeks. In the depressed state patients exhibited significantly smaller CNVs than the controls. In the AT-group clinical improvement and drug plasma levels of nortriptyline (NT, the principal metabolite of AT and an active antidepressant by itself) were positively related to increases in CNV-area; in the OT-group the reverse was true: increase in CNV-area was related to smaller OT plasma levels and less favourable outcome. The control group displayed a steady decline in CNV area during the 3 test sessions. N1P2 amplitude and PINV were not significantly different between groups and exhibited only minor variations during treatment.

Adult↗
PubMed1978

Determination of amitriptyline and nortriptyline in human plasma by quantitative thin-layer chromatography.

A thin-layer chromatographic method for simultaneous determination of amitriptyline (AT) and nortriptyline (NT) in human plasma is described. Both substances are extracted from biological material by means of a single extraction. The extract is evaporated until dry and the residue quantitatively applied to a silica gel thin-layer plate. AT and NT are separated from interfering plasma components by chromatography. The spots are visualized by nitration, reduction and coupling with N-(1-naphtyl)ethylenediamine on the plate. The intensity of the azo-dyes formed can be measured densitometrically. Using 1 ml of plasma, the sensitivity limit was 0.5 ng/ml for both substances. About 10--15 plasma samples can be analysed per day. The method is applicable to pharmacokinetic studies after a single oral dose of 25 mg AT as hydrochloride in man.

Amitriptyline↗
PubMed1979

Reliable routine method for the determination of plasma amitriptyline and nortriptyline by gas chromatography.

A gas chromatographic method has been developed for the determination of amitriptyline and nortriptyline in plasma. OV-17 is used in a 1 m long packed column, with a flame ionization detector and an electronic integrator. Five internal standards are added. The base-specific extraction procedure and the method of calibrating the chromatograph are described in detail. The accuracy, precision and reliability of the method are demonstrated by the results of nearly 700 determinations of each drug, at concentrations ranging from 5 to 400 ng/ml in the plasma. An interlaboratory comparison with a double radioactive isotope derivative assay for nortriptyline has also shown satisfactory agreement.

Amitriptyline↗
PubMed1984

Gas chromatographic--mass spectrometric determination of amitriptyline and its major metabolites in human serum.

A gas chromatographic--electron-impact ionization mass spectrometric method has been developed for the determination of amitriptyline (AMT) and its metabolites, nortriptyline (NT), 10-hydroxyamitriptyline (10-OH-AMT) and 10-hydroxynortriptyline (10-OH-NT) in human serum. The lower limit of detection was 2 ng/ml for all compounds except 5 ng/ml for 10-OH-NT. The calibration curves for AMT and 10-OH-AMT were linear up to 100 ng/ml, and up to 200 ng/ml for NT and 10-OH-NT. The accuracy of the assay in terms of coefficient of variation was less than 7%. The extraction efficiency was almost quantitative for all compounds except 60% for 10-OH-NT. Using this method, human serum samples which had been collected after oral administration of a single 50-mg dose of AMT were analyzed. Ratios of the conjugation of each metabolite were estimated, including AMT.

Amitriptyline↗