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Sinequan

Generic Sinequan is used for treating depression or anxiety in certain patients. It may also be used for other conditions. Generic Sinequan is a tricyclic antidepressant. It increases the activity of certain chemicals in the brain, which help elevate mood.

Other names for this medication:

Similar Products:
Anafranil, Norpramin, Noveril, Lomont, Pamelor, Aventyl, Norpress

 

Also known as:  Doxepin.

Description

Generic Sinequan is a tricyclic antidepressant. It increases the activity of certain chemicals in the brain, which help elevate mood.

Generic name of Generic Sinequan is Doxepin.

Sinequan is also known as Doxepin, Aponal, Deptran, Doneurin, Doxin, Mareen, Quitaxon, Sinepin, Spectra, Xepin.

Brand name of Generic Sinequan is Sinequan.

Dosage

Take Generic Sinequan by mouth with or without food.

Taking Generic Sinequan at bedtime may help reduce side effects (eg, daytime drowsiness).

If you want to achieve most effective results do not stop taking Generic Sinequan suddenly.

Overdose

If you overdose Generic Sinequan and you don't feel good you should visit your doctor or health care provider immediately.

Storage

Store at room temperature between 15 and 30 degrees C (59 and 86 degrees F) away from moisture and heat. Throw away any unused medicine after the expiration date. Keep out of the reach of children.

Side effects

The most common side effects associated with Sinequan are:

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Side effect occurrence does not only depend on medication you are taking, but also on your overall health and other factors.

Contraindications

Do not take Generic Sinequan if you are allergic to Generic Sinequan components.

Be careful with Generic Sinequan if you are pregnant, planning to become pregnant, or are breast-feeding.

Do not take Generic Sinequan if you take clonidine, an H1 antagonist (eg, astemizole, terfenadine), or ibutilide, or you have taken a monoamine oxidase inhibitor (MAOI) (eg, furazolidone, phenelzine, isocarboxazid) within the past 14 days.

Do not take Generic Sinequan if you have certain prostate problems (eg, asymptomatic prostatic hypertrophy), glaucoma, or trouble urinating.

Be careful with Generic Sinequan if you have a history of heart problems, seizures (eg, epilepsy), overactive thyroid, prostate problems (eg, benign prostatic hypertrophy [BPH]), blood problems (eg, porphyria), other mental or mood problems, suicidal thoughts or attempts, or alcohol abuse.

Be careful with Generic Sinequan if you take antiarrhythmics (eg, quinidine, propafenone, flecainide), antifungal medicines (eg, fluconazole, terbinafine), carbamazepine, cimetidine, mibefradil, phenothiazines (eg, chlorpromazine, thioridazine), or selective serotonin reuptake inhibitors (SSRIs) (eg, fluoxetine, sertraline) because they may increase the risk of Generic Sinequan 's side effects; anticoagulants (eg, warfarin), H1 antagonists (eg, astemizole, terfenadine), ibutilide, sulfonylureas (eg, tolazamide, glipizide), sympathomimetics (eg, phenylephrine, pseudoephedrine), or tramadol because the risk of their side effects may be increased by Generic Sinequan; clonidine, guanadrel, guanethidine, or guanfacine because their effectiveness may be decreased by Generic Sinequan; MAOIs (eg, furazolidone, phenelzine, isocarboxazid) because severe toxic effects may occur.

Avoid alcohol.

Be careful when you are driving or operating machinery.

It can be dangerous to stop Generic Sinequan taking suddenly.

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In this 2-night study of elderly adults with primary insomnia, doxepin doses of 1 mg, 3 mg, and 6 mg were well tolerated and produced significant improvement in objective and subjective sleep maintenance and duration endpoints that persisted into the final hour of the night. Positive effects on patient-reported sleep onset were observed at the highest dose. All 3 doxepin doses had a safety profile comparable to placebo. These data demonstrate that doxepin was efficacious in improving sleep in elderly adults.

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A simple normal-phase (silica), high-performance liquid chromatographic (HPLC) assay of amitriptyline (AMI), doxepin (DOX), imipramine (IMI), nortriptyline (NORT), desmethyldoxepin (DESDOX), desipramine (DESIP), and protriptyline (PRO) in serum with no coelution is described here. Trimipramine and promazine were used as internal standards. Extraction of the 1.0-ml serum samples (collected in plastic) was done with Bond-Elut C18 columns. The compounds of interest were eluted with 10 mM methanolic ammonium acetate. The eluates were evaporated at 56-58 degrees C and reconstituted with 200 microliters of the mobile phase. The mobile phase was absolute ethanol-acetonitrile-tert-butylamine (98:2:0.05, vol/vol/vol). Detection of eluted drugs was at 254 nm at 0.01 absorbance units full scale (AUFS), except for PRO, which was detected at 229 nm at 0.02 AUFS. Absolute recoveries were 87-97%. A 5-micron silica (4.6 X 250 mm) HPLC column was used; results with a 10-micron silica column (3.9 X 300 mm) are also presented. Peak height ratios with trimipramine were linear for each analyte between 25 and 1200 ng/ml. Peak height ratios with promazine as the internal standard were linear for each analyte between 25 and 600 ng/ml. Detection limits under the conditions described were 2 ng/ml for AMI, DOX, and IMI, 4 ng/ml for NORT, DESDOX, and DESIP, and 10 ng/ml for PRO. Coefficients of within-day and day-to-day variation at three concentration levels were less than 9.8% and less than 11.2%, respectively. The hydroxylated metabolites of IMI, DES, NORT, and the cis isomer of DOX are discussed. Steady-state daily dosages and corresponding serum levels are presented for 69 patients. The total assay time was less than 10 min for DESIP and 12 min for PRO. This assay can be used in correlating serum levels with clinical effects, compliancy, and pharmacokinetic studies.

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Age-related changes in histamine H1 receptors were studied using [11C]pyrilamine or [11C]doxepin by positron emission tomography (PET). The frontal, parietal and temporal cortices showed age-related decreases in binding of approximately 13% per decade. In contrast, the thalamus showed no apparent decrease in binding during normal ageing because of its higher nonspecific binding. Post mortem studies also indicated that the nonspecific binding of [3H]pyrilamine in the thalamus was approximately 112% higher than that in the cortex. However, no significant decrease in histamine H1 receptors with age was observed by in vitro binding assays of autopsied human frontal cortex. Possible reasons are given for the larger effects of age observed in the PET study than in the in vitro post mortem binding study.

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Twenty healthy subjects took amitriptyline, doxepin, and placebo for 2 wk each in a double-blind crossover trial, and another 20 subjects similarly took nortriptyline, chlorimipramine, and placebo. The antidepressants were given three times daily in doses generally used for neurotic patients. The presence of antidepressants in tissues was checked with the tyramine pressor test. On the seventh and fourteenth days of each period, psychomotor skills (choice reaction, coordination, and attention) were measured after the administration of drugs in combination with an alcoholic or placebo drink. Dose-response graphs for the tyramine pressor effect were shifted to the right during the antidepressant treatment, indicating a blockade of the membrane pump in peripheral sympathetic terminals. This antityramine effect of antidepressants did not correlate with their psychomotor effects. No drug alone importantly impaired psychomotor skills. Amitriptyline in combination with alcohol increased cumulative choice reaction times, and doxepin in combination with alcohol increased both cumulative choice reaction times and inaccuracy of reactions. Coordination was impaired after both of these combinations on the seventh day. It seems as if doxepin and amitriptyline but not nortiriptyline or chlorimipramine, in combination with 0.5 gm/kg of alcohol, may be especially dangerous in driving.

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We searched the Cochrane Tobacco Addiction Group trials register which includes trials indexed in Medline, Embase, SciSearch and PsycLit, and meetings abstracts.

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In 92 patients (22 females and 70 males) with unipolar affective disorder hemodynamic studies using a radiocardiographic method were performed during treatment of a depressed phase of illness with amitriptyline or doxepin or mianserin. Frequent presentation of hemodynamic disturbances (increased heart rate and increased blood pressure) in the course of endogenous depression was noticed. Thymoleptic treatment causes the disturbances to alter in a statistically significant manner which allows to predict the final treatment outcome. Total Peripheral Resistance Index (TPRI) reveals the highest prognostic potential.

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We extracted data in duplicate on the type of study population, the nature of the drug therapy, the outcome measures, method of randomisation, and completeness of follow-up. The main outcome measure was abstinence from smoking after at least six months follow-up in patients smoking at baseline. We used the most rigorous definition of abstinence for each trial, and biochemically validated rates if available. Where appropriate, we performed meta-analysis using a fixed effects model.

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(11)C-Doxepin was radiosynthesized by N-[(11)C]methylation of nordoxepin using [(11)C]methyl iodide in DMF solvent, and then purified by HPLC, and finally reformulated with solid phase extraction (SPE) using a cGMP-compliant automated multipurpose PET module developed in house. The final product was analyzed and subjected to quality control according to current US Pharmacopeia requirements.

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A controlled double-blind study of 40 depressed psychiatric outpatients who received doxepin either q.i.d. or h.s. showed that doxepin may be administered h.s. without loss of efficacy or increase in side effects. The patients who received doxepin h.s. felt significantly better rested in the morning than the patients who received doxepin in divided doses.

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Chronic urticaria (CU) imposes profound impairment on quality of life. Up to 60% of idiopathic CU is associated with autoimmune phenomena, and may respond to immunomodulation. Hydroxychloroquine offers potential efficacy for CU and is relatively benign compared with most other therapeutic approaches.

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A total of 975 elderly patients with GAD were identified. Mean age was 75 years, and 72% were women; 29% had diagnoses of comorbid depression. Forty percent of study subjects received potentially inappropriate agents - most commonly, bromazepam (10% of all subjects), diazepam (9%), doxepin (7%), amitriptyline (5%), and lorazepam (5%). Twenty-three percent of study subjects received long-acting benzodiazepines, 10% received short-acting benzodiazepines at relatively high doses, and 12% received TCAs designated as potentially inappropriate.

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Mice were given a drug per os and 2 h later were challenged with an intravenous LD95 of nicotine. Amitriptyline, imipramine, doxepin, meprobamate, chlordiazepoxide, diazepam, trifluoroperazine, haloperidol, thioridazine, chlorpromazine, phenobarbital, propranolol and diphenylhydantoin were all active in protecting mice from extensor convulsions and lethality. Iproniazid, tranylcypromine, atropine, benztropine and trimethadione were inactive. There appears to be a relationship between blockage of nicotine-induced extensor convulsions and lethality in mice and sedative-antianxiety effects in man. This relationship is especially good for drugs designated antidepressant, antianxiety and antipsychotic.

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A fast and selective ultraperformance liquid chromatographic-tandem mass spectrometric method was developed and validated for the simultaneous quantification of amitriptyline, citalopram, clomipramine, desipramine, desmethylcitalopram, desmethylclomipramine, desmethyldosulepin, desmethyldoxepin, desmethylfluoxetine, desmethylvenlafaxine, didesmethylcitalopram, dosulepin, doxepin, duloxetine, fluoxetine, fluvoxamine, imipramine, maprotiline, mianserin, mirtazapine, moclobemide, nortriptyline, paroxetine, reboxetine, sertraline, trazodone, and venlafaxine in 100 μL of plasma. After liquid-liquid extraction with 1-chlorobutane, analytes were separated on a BEH (Ethylene Bridged Hybrid) C18 analytical column with gradient elution. The compounds were ionized and detected over 7-minute analysis time by electrospray ionization tandem mass spectrometry with multiple reaction monitoring. Limits of quantification and limits of detection ranged from 2.5 to 10 ng/mL and 0.2 to 10 ng/mL, respectively. Intra- and interassay imprecision were lower than 15% for all the compounds except for mirtazapine, moclobemide, and desmethylclomipramine [relative standard deviation (RSD) < 20%], and the bias of the assay was lower than 15% for all the compounds except for fluvoxamine (bias < 20.5%), evaluated with 5 commercial quality control and 3 "in-house" quality control. The extraction was found to be reproducible (RSD < 16%) (except for duloxetine RSD 21.9%) and with recoveries varying from 59% to 86%. Furthermore, the stability studies demonstrated that the processed samples were stable in the autosampler for 24 hours for all the compounds. The method was successfully applied to the analysis of authentic samples from forensic toxicology cases and external quality control assays from the Society of Toxicology and Forensic Chemistry (GTFCh). The method was completely validated and can be of interest to clinical and forensic laboratories.

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Despite the introduction of numerous new agents, tricyclic antidepressants remain an important option for the treatment of depression. Doxepin is still in wide use, and determining its concentration is a standard procedure in many psychiatric clinics. Some widely cited reviews indicate a therapeutic range from 150 to 250 ng/mL (parent plus desmethyl metabolite). The vast majority of the authors' patients fell short of these concentrations under customary doses. To resolve this issue, the authors' serum-level databank was analyzed, a questionnaire was sent to U.S. and German psychiatric university departments and laboratories, and the literature was reviewed. The main results were the following: (1) Only 9% of all samples analyzed (N = 217) displayed plasma levels (high-performance liquid chromatography) between 150 and 250 ng/mL; 88% were subtherapeutic. The mean doxepin + desmethyldoxepin steady-state serum concentration was 89+/-75 ng/mL (N = 32, doxepin >3 weeks). The mean daily dose was 143+/-30 mg. There was no correlation between concentrations and improvement. (2) A wide variety of recommendations is given by the different university departments (10-1,000 ng/mL). (3) According to the studies published to date, there is not enough evidence for recommending a therapeutic range. The preliminary suggestions given in some influential reviews have been widely adopted without critical re-evaluation. Compared with the concentrations found in the original studies, the therapeutic ranges suggested are too high. A methodologically sound study to determine a therapeutic range is required for the rational monitoring of this drug. Meanwhile, a preliminary working range of 50 to 250 ng/mL is proposed on the basis of critical reassessment of published data.

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Although the frequent coexistence of substance abuse and depression is widely recognized, studies assessing the efficacy of tricyclic antidepressants in patients who abuse alcohol and/or drugs have been problematic because of controversies about how to diagnose depression in this population, failure to measure plasma antidepressant levels, and inconsistent treatment outcome measures. Some studies have, however, demonstrated the effective use of specific tricyclic antidepressants in selected subgroups of substance abusers; for example, desipramine may facilitate initiation of cocaine abstinence, and doxepin may benefit certain opioid addicts. Although imipramine has shown only equivocal success in the treatment of alcoholics, preliminary studies of serotonin uptake inhibitors show some promise in this population. As research design in this field becomes more consistent, future studies may more clearly identify subgroups of chemically dependent patients who respond to specific antidepressant drugs.

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Elephantiasis nostras (EN) is a clinical entity that usually presents as a persistent swelling of the lower extremities. It has been related to recurrent lymphangitis of bacterial origin that causes a fibrosis and thickening of both epidermal and connective tissue. Although very rare, EN has been previously reported in the lips. This is the first case reported in the oral medicine literature that describes EN involving the lips. We describe the clinical features and a differential diagnosis of the lip lesions and a treatment protocol to which this patient has responded. A diagnosis of EN should be entertained in patients with chronically edematous, scaling lip lesions.

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This randomized, double-blind, crossover study used PET imaging with [(11) C]-doxepin to evaluate H1 RO in 12 healthy males (mean age 26.2 years), after single oral administration of bilastine (20 mg), hydroxyzine (25 mg) or placebo. Binding potentials and H1 ROs were calculated in five cerebral cortex regions of interest: frontal, occipital, parietal, temporal, insula. Plasma bilastine concentrations, subjective sedation (visual analogue scale), objective psychomotor performance (digital symbol substitution test), physiological variables and safety (adverse events, AEs), were also evaluated.

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Despite some evidence that neuroleptic medication is overused or misused in long-term care facilities for the elderly, there has been virtually no attention paid to the pattern of use of antidepressants in these facilities. All patients in long-term care in a geriatric hospital and a home for the aged who were receiving antidepressants were identified; 10.5% of the patients in the hospital and 12.7% in the home for the aged were receiving an antidepressant. The rate of use of antidepressants on the different units ranged from 0% to 26.8%. The most commonly prescribed antidepressant was doxepin followed by nortriptyline. The mean dose of antidepressant was 34.8 mg. Although depression was the most common reason for the prescription of an antidepressant (69% of patients receiving one), other reasons included pain, agitation, aggression, and insomnia. Patients had been receiving antidepressants for up to 10 years, with a mean duration of 32 months. The majority of patients (60%) had a history of depression predating their institutional admission. Patients receiving antidepressants were compared to a group not receiving antidepressants, who were matched for age, sex, unit, and attending physician. Patients receiving antidepressants were more likely to have a history of stroke (33.8% versus 16.9%). There was no significant difference between the two groups regarding the prevalence of dementia, Parkinson's disease, thyroid disease, malignant tumor, congestive heart failure, or diabetes mellitus. Prospective studies are required to determine the efficacy of antidepressants in this population and to identify factors that can predict a positive response to treatment.

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Three patients taking conjugated estrogens developed akathisia induced by tricyclic antidepressants. The interaction between tricyclic antidepressants and conjugated estrogens could play a role in the development of akathisia.

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Major improvements in the quality of recent pharmacologic studies of rhinitis are evident. In many of the studies, the criteria for patient selection are being more carefully described and patients with allergic rhinitis, nonallergic rhinitis with eosinophilia, and vasomotor rhinitis are no longer grouped together. In most studies, efficacy is still being ascertained by subjective symptom scores, although in some of the challenge studies, investigators are making noble attempts to quantitate symptoms objectively, eg, amount of secretions, sneezing, and even itching of the nares. Although nasal congestion is only one symptom of chronic rhinitis, the various methods of measuring nasal resistance by rhinometry are increasingly well described and standardized. General concepts that are emerging from the vast literature on pharmacologic treatment of rhinitis are as follows: 1) The much-maligned H1 receptor antagonists may actually be more useful than previously thought, once further information about how to use them optimally is available. Interesting new antihistamines are being developed. Further investigations of allied drugs such as the tricyclic antidepressants (doxepin) are definitely in order. 2) alpha-adrenergic agonists definitely have short-term usefulness but side effects from this class of drugs have, if anything, been underestimated. Exploration of the use of beta-adrenergic agonists and anti-cholinergics in the treatment of chronic rhinitis has begun. 3) Disodium cromoglycate is not universally effective in chronic rhinitis, perhaps in part because compliance with a prophylactic drug requiring insufflation four or six times daily may not be high. The degree of response and the percentage of patients having an excellent response to the drug is lower than for the new corticosteroids. 4) Topical corticosteroids administered intranasally are clearly the most effective medications for treatment of chronic rhinitis. Further study of the benefit versus the long-term risk of these drugs is mandatory, but their remarkable efficacy and safety in the treatment of chronic rhinitis is undisputed. Some comparisons between the four major groups of drugs are now being made, and further attempts to define the relative roles and the interactions of drugs used in the pharmacologic treatment of rhinitis are definitely needed.

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H(1)RO after bepotastine treatment was significantly lower than that after diphenhydramine treatment in all cortical regions (P < 0.001). Mean H(1)ROs of bepotastine and diphenhydramine were 14.7% and 56.4%, respectively. H(1)ROs of both bepotastine and diphenhydramine correlated to their respective drug plasma concentration (P < 0.001).

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A procedure is described for extracting doxepin, a tricyclic antidepressant, from plasma and subsequently measuring its concentration by GLC. The developed technique permits the resolution and quantitative determination of the cis- and trans-isomers of doxepin as well as its desmethyl metabolite. The method allows precise, reliable measurement of the drug and one of its metabolities in concentrations as low as 10 ng/ml of plasma.

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Intoxication with antidepressants should not be excluded a priori in a hypothermic patient who displays other clinical signs of the said intoxication.

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Depression is a psychiatric condition that affects about 120 million people worldwide and can interfere with independence and productivity in essentially all aspects of daily life. Depression is also associated with risk of self-harm, and ultimately suicide. Antidepressant medications are widely used to treat symptoms of depression. While there are several classes of antidepressants, therapeutic drug management (TDM) is most common for the tricyclic antidepressants (TCAs). TDM of TCAs is important due to wide inter-individual variability in pharmacokinetics, production of active metabolites, and a high risk of drug-drug interactions. In addition, TDM of some TCAs can be used to optimize dose, wherein concentration relationships are recognized for both therapeutic response and potentially life-threatening toxicity. In many clinical scenarios, TDM of TCAs is accomplished by currently available point of care or automated immunoassays that provide a "total" TCA concentration. However, these assays may not be adequately specific to meet the needs of all clinical scenarios, and hence, chromatographic separation and quantification of individual TCA parent drugs and active metabolites that may contribute to the "total" TCA concentration is sometimes required. This chapter describes an analytical method designed to detect and/or quantify clinically significant concentrations of nine TCAs (amitriptyline, nortriptyline, imipramine, desipramine, doxepin, nordoxepin, protriptyline, clomipramine, and norclomipramine) in serum or plasma, using ultra pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The sample preparation employs a rapid protein precipitation with 50:50 MeOH:acetonitrile, high speed centrifugation, and injection of 5 μL of supernatant onto the instrument, with a 5 min run-time.

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30 inpatients suffering from major depression (DSM-III-R), who did not fulfill the criteria of seasonal affective disorder (SAD), were treated with either doxepin or amitripytyline as monotherapy and supportively with bright light for 14 days. From days 15 to 19, bright light was replaced by dim light. 18 drug-free control subjects underwent an analogous sequence of bright- and dim-light applications. Phototherapy was applied between 06:00 and 07:30. Heart-rate (HR) analysis was performed in the patients and control subjects before and after the 5th session of bright and dim lights, respectively. 12 patients (40%) experienced improvement of mood during bright-light therapy (group I) while 18 (60%) did not (group II). Patients of group I, who reached significantly higher scores in the seasonal pattern assessment questionnaire than patients of group II, showed an increase of the coefficient of HR variation (HRV) during deep breathing as well as an increment of the high-frequency (HF) peak of spectral analysis exclusively after the bright-light sessions. Patients of group II did not show a significant alteration of these parameters, neither under the conditions of bright-light treatment nor under dim light. The control subjects experienced an increment of the HF power exclusively after bright light. The results suggest that a distinct subgroup of patients with non-SAD major depression shows a more pronounced light-associated increment of parasympathetically controlled cardiac functions than the other depressed patients and the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

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In blood platelets of untreated patients with endogenous depression a significantly lower concentration of serotonin (5-HT) was found than in healthy persons (P less than 0.05). The patients were afterwards divided into two groups: group I with mild symptoms of depression (total scores by Hamilton Depression Rating Scale below 40) and group II with severe depression (total scores above 40). The gradual diminishing of symptoms in both groups was accompanied by no change in 5-HT level in the first group and by progressive and well marked increases in platelet 5-HT content in the second one, attaining average normal values at the end of week 3 of treatment with maprotiline. In in vitro experiments maprotiline inhibited the uptake of 5-HT into blood platelets of healthy persons less than doxepin. After injection of maprotiline in rats (50 mg/kg IP) the turnover rate of 5-HT in the brain was only marginally affected if measured by 5-HT rise and 5-hydroxyindoleacetic acid (5-HIAA) decline after administration of the MAO inhibitor pargyline, or by estimation of 5-HIAA increase after blocking active transport with probenecid. However, after treatment with maprotiline alone, the 5-HIAA level in the rat brain was significantly increased, although the concentration of 5-HT was not altered. These results suggest: a) the possibility of an action of maprotiline on serotoninergic neurons and b) the suitability of blood platelets as a model for such an investigation.

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Blood glucose level (BGL) was estimated up to 4 h (3 h in case of GTT) in 18-h fasted albino rabbits following acute and chronic (one month) feeding of doxepin and thereafter for another 8 days together with either insulin or glibenclamide or adrenaline. A single dose of doxepin produced significant hypoglycemia which peaked at 4 h and lasted up to 10 h. On chronic doxepin feeding there was complete attenuation of initial hypoglycemia on the 7th and 14th days, culminating into frank hyperglycemia on the 21st day. However, there was complete recovery on the 29th day exhibiting tolerance to initial hypo-as well as delayed hyperglycemia. Similarly, glucose intolerance was accentuated on the 8th day followed by a gradual recovery on the 15th and 22nd days, culminating in disappearance of glucose intolerance on the 30th day. The hypoglycemic effect of insulin was markedly potentiated in chronically doxepin fed animals which was further enhanced on continuing administration of both agents. Profound hypoglycemia was observed during GTT in such animals. The hyperglycemic effect of adrenaline was enhanced in chronically doxepin fed animals, which may be due to TCA induced enhancement of the response of exogenous adrenaline. Suppression of this hyperglycemia with continued administration of both drugs seems to be due to subsensitivity of alpha 2-adrenoceptors. Additive hyperglycemia was observed during GTT in such animals.

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The conversion of tertiary amines to quaternary ammonium glucuronides was investigated in human liver microsomes, and characteristics of the UDP-glucuronosyltransferase (UGT) catalyzing quaternary ammonium glucuronidation were evaluated. In addition, a rabbit liver microsomal UGT mediating this reaction was studied. The kinetics of quaternary ammonium glucuronidation of cyproheptadine, tripelennamine, amitriptyline, and doxepin in intact human liver microsomes was determined. Tripelennamine was found to have the lowest apparent KM and was used as a representative substrate for further studies. A polyclonal antibody preparation raised in sheep against rabbit liver p-nitrophenol UGT was found to inhibit tripelennamine glucuronidation in solubilized human liver microsomes, but had no effect on p-nitrophenol, 4-methylumbelliferone, 4-aminobiphenyl, estriol, morphine, or naloxone glucuronidation. This antibody also inhibited tripelennamine glucuronidation in solubilized rabbit liver microsomes, but had little or no effect on estrone, testosterone, estradiol, androsterone, and morphine glucuronidation. Chlorpromazine competitively inhibited tripelennamine glucuronidation. This inhibition was markedly enhanced by UV light irradiation. [3H] Chlorpromazine binding to solubilized human liver microsomes was also increased by UV light. The binding was antagonized by substrates for tertiary amine UGT but not by substrates for morphine UGT. These studies suggest that the tertiary amine UGT is photo-affinity-labeled by chlorpromazine. Furthermore, it would appear from immunoinhibition and [3H]chlorpromazine labeling experiments that tertiary ammonium glucuronidation is catalyzed by a unique and distinct UGT in rabbit and human liver microsomes.

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Using radioligand binding techniques, we determined the equilibrium dissociation constants (KDS) for a series of antidepressants at the histamine H1, muscarinic acetylcholine, alpha-1 and alpha-2 adrenergic and dopamine (D-2) receptors of normal human brain tissue obtained at autopsy. Twenty-five different antidepressants were studied at all but the D-2 receptor at which the number was 13 (including a metabolite of an antidepressant). Of all the receptor interactions studied, that at the histamine H1 receptor was in general the most potent interaction of this class of compounds, corresponding to results from studies using animal tissue as the source of receptors. At the human brain histamine H1 receptor, antidepressants remained among the most potent histamine H1 antagonists known, although their affinities for human receptors were lower than those for animal receptors. The most potent and the least potent compounds at the receptors were doxepin (KD = 0.24 nM) and fluvoxamine (KD = 109 microM) at the histamine H1 receptor, amitriptyline (KD = 18 nM) and trazodone (KD = 324 microM) at the muscarinic receptor, doxepin (KD = 24 nM) and viloxazine (KD = 14 microM) at the alpha-1 receptor, mianserin (KD = 73 nM) and bupropion (KD = 81 microM) at the alpha-2 receptor and amoxapine (KD = 160 nM) and trazodone (KD = 3800 nM) at the D-2 receptor, respectively. In general, compared to older drugs, the newer compounds tended to have lower affinities for these receptors.

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sinequan and alcohol 2016-12-31

Doxepin is a tricyclic antidepressant buy sinequan with a subnanomolar affinity for the histamine H(1) (H(1)) receptor. It has a long history of use for depression at doses higher than those needed for antagonism of H(1) receptors. Recent work has focused on its use at low doses (1, 3 and 6 mg) in patients with chronic primary insomnia. Two phase II studies and four phase III studies have investigated its efficacy on both objective and subjective sleep measures in both adults and elderly patients. It was effective on a variety of sleep onset, maintenance and early awakening outcomes and had minimal effects on sleep architecture. There was no signal for tolerance, psychomotor impairment, residual sedation, rebound insomnia or discontinuation symptoms in trials of up to 3 months duration. Doxepin was well tolerated; sedation/sleepiness and headache were the most common adverse events but these were mainly at placebo level or less. Further work is required to establish doxepin's low-dose effect on hypnotic activity.

sinequan medication 2017-09-04

The combined application of RTX and antidepressants produced a markedly prolonged nociceptive peripheral nerve block in rat sciatic nerves compared with either agent alone. However, the 2-drug regimen also elicited prolonged blockade of the motor function buy sinequan , although disproportionately less compared with the nociceptive modality, suggesting the existence of nontransient receptor potential vanilloid type 1-mediated mechanisms. The mechanisms through which RTX affects nociceptive signal transduction/transmission have yet to be fully elucidated.

sinequan cost 2015-12-27

Twenty-four-hour HRV measures may be useful in buy sinequan assessing response to antidepressant therapy.

sinequan dosage 2016-12-19

Results from two separate studies were combined to compare the acute and subchronic effects of two monoamine oxidase-A (MAO-A) inhibitors, moclobemide and brofaromine, on actual driving performance and sleep. Both studies were conducted according to a double-blind, crossover design involving 18 patients receiving moclobemide and 16 patients receiving brofaromine. Patients were administered either moclobemide 200 mg b.i.d., mianserin 10 buy sinequan mg. t.i.d., and placebo (study 1), or brofaromine 50 and 75 mg b.i.d., doxepin 25 mg t.i.d., and placebo (study 2) for 8 consecutive days. A standardized driving test was conducted on day 1 and day 8 of treatment. Daily logs of estimated sleep duration and quality were obtained. Neither moclobemide nor brofaromine impaired driving performance. Some indication, although statistically not significant, was found that moclobemide improved driving performance on day 1. Brofaromine 75 mg significantly improved driving performance on day 8 of treatment. No significant difference between the effects of both drugs was found in a cross-study comparison. Moclobemide did not affect any sleep parameter, whereas brofaromine shortened sleep duration and decreased sleep quality. On day 1, mianserin and doxepin impaired driving. Impairment dissipated after 8 days of treatment with doxepine but not during treatment with mianserin. Sleep duration was prolonged during treatment with both drugs, whereas sleep quality remained unaffected. It is concluded that both MAO-A inhibitors are safe drugs with respect to driving.

sinequan generic 2017-02-05

A neural-network analysis has been applied to predict adverse or side effects of drugs using a database of antidepressant agents with known effects as well as input from a database with both buy sinequan patient parameters and drug information. A NeuralWork software package was implemented on a Macintosh Quadra 700 and trained on a database of ten drugs with known adverse effects. Another agent (not in the database) was used to test the ability of the network to predict the relative incidence of its side effects. Despite the small number of drugs used for training, the adverse effects of some drugs, such as doxepin, were predicted with 90-100% accuracy. These results indicate that neural-network analysis can be used to predict adverse drug effects for drugs within a given class and ultimately can be extended to include patient parameters to predict the mechanisms of action of drugs from relatively large databases.

sinequan buy 2015-06-06

Although the tricyclic antidepressant drugs imipramine and doxepin exert similar direct buy sinequan electrophysiological effects on cardiac cells, toxic cardiac arrhythmias and conduction disturbances are much more commonly associated with imipramine than doxepin in clinical use. To ascertain if this discrepancy could be due to different cellular electrophysiological actions of active metabolites of imipramine and doxepin, the effects of desmethylimipramine (DMI) and desmethyldoxepin (DMD) on isolated, superfused, canine cardiac Purkinje fibers were studied by glass microelectrodes and programmed stimulation. At a concentration of 50 ng/ml neither DMI nor DMD affected the resting membrane potential (RMP), action potential amplitude (Amp), maximum upstroke velocity of phase 0 (Vmax), action potential duration to repolarization to 50 and 100% of the amplitude (APD50, APD100), effective refractory period (ERP), or conduction velocity (CV). At 250 ng/ml neither drug affected Amp, APD100, or CV; both compounds reduced APD50 by 10 to 15%; and DMD but not DMI caused small reductions of RMP, Vmax, and ERP. At 1000 ng/ml neither DMI nor DMD affected RMP but both caused more marked reductions of APD50 (31 to 35%) and ERP (21 to 23%). At this concentration both substances also reduced Amp by 6 to 7%, Vmax by 28 to 35%, APD100 by 7 to 12%, and CV by 15 to 25%. These effects of DMI and DMD are similar to those produced by the parent drugs. Differences in cardiotoxicity between imipramine and doxepin in clinical use are probably not due to different direct cellular electrophysiological effects of the circulating demethylated metabolites of these drugs.

sinequan 50 mg 2016-07-01

All patients admitted to the Royal Infirmary of buy sinequan Edinburgh between 1 January 2000 and 31 December 2002 with an overdose involving an antidepressant.

sinequan 200 mg 2015-03-05

DXP 3 mg led to significant improvement versus PBO on N1 in wake time after sleep onset (WASO; P < 0.0001; primary endpoint), total sleep time (TST; buy sinequan P < 0.0001), overall sleep efficiency (SE; P < 0.0001), SE in the last quarter of the night (P < 0.0001), and SE in Hour 8 (P < 0.0001). These improvements were sustained at N85 for all variables, with significance maintained for WASO, TST, overall SE, and SE in the last quarter of the night. DXP 3 mg significantly improved patient-reported latency to sleep onset (Weeks 1, 4, and 12), subjective TST (Weeks 1, 4, and 12), and sleep quality (Weeks 1, 4, and 12). Several global outcome-related variables were significantly improved, including the severity and improvement items of the CGI (Weeks 2, 4, and 12), and all 5 items of the PGI (Week 12; 4 items after Weeks 2 and 4). Significant improvements were observed for DXP 1 mg for several measures including WASO, TST, overall SE, and SE in the last quarter of the night at several time points. Rates of discontinuation were low, and the safety profiles were comparable across the 3 treatment groups. There were no significant next-day residual effects; additionally, there were no reports of memory impairment, complex sleep behaviors, anticholinergic effects, weight gain, or increased appetite.

sinequan user reviews 2016-02-07

There are at least two theoretical reasons to believe antidepressants might help in smoking cessation. Nicotine withdrawal may produce depressive symptoms or precipitate a major depressive episode and antidepressants may relieve these. Nicotine may have antidepressant effects that maintain buy sinequan smoking, and antidepressants may substitute for this effect. Alternatively, some antidepressants may have a specific effect on neural pathways underlying nicotine addiction, (e.g. blocking nicotine receptors) independent of their antidepressant effects.

sinequan doxepin reviews 2015-06-01

Delusions of parasitosis are a rare psychiatric disorder in which the patient has a fixed, false belief of being infested with parasites. The disorder is classified as primary if no cause is identified or secondary if associated with general organic conditions, psychiatric illnesses, and drugs (substance induced). Several medications have been reported in buy sinequan association with delusions of parasitosis, including anti-parkinsonian medications, ciprofloxacin, cetirizine, doxepin, and others. Delusions of parasitosis have not been previously reported to be associated with gabapentin use. We present the case of a patient who developed delusions of parasitosis after been initiated on gabapentin treatment for neuropathic pain and complete disappearance of symptoms after the medication was discontinued.

sinequan mg 2017-12-16

A managed care plan for individuals meeting nursing home eligibility. buy sinequan

sinequan 25 mg 2015-11-20

A total of 975 elderly patients with GAD were identified. Mean age was 75 years, and 72% were women; 29% had diagnoses of comorbid depression. Forty percent of study subjects received potentially inappropriate agents buy sinequan - most commonly, bromazepam (10% of all subjects), diazepam (9%), doxepin (7%), amitriptyline (5%), and lorazepam (5%). Twenty-three percent of study subjects received long-acting benzodiazepines, 10% received short-acting benzodiazepines at relatively high doses, and 12% received TCAs designated as potentially inappropriate.

sinequan lethal dose 2017-02-25

From pharmacological studies using histamine antagonists and agonists, it has been demonstrated that histamine modulates many physiological functions of the hypothalamus, such as arousal state, locomotor activity, feeding, and drinking. Three kinds of receptors (H1, H2, and H3) mediate these actions. To define the contribution of the histamine H1 receptors (H1R) to behavior, mutant mice lacking the H1R were generated by homologous recombination. In brains of homozygous mutant mice, no specific binding of [3H]pyrilamine was seen. [3H]Doxepin has two saturable binding sites with higher and lower affinities in brains of wild-type mice, but H1R-deficient mice showed only the weak labeling of [3H]doxepin that corresponds to lower-affinity binding sites. Mutant mice develop normally, but absence of H1R significantly increased the ratio of ambulation during the light period to the total ambulation for 24 hr in an accustomed environment. In addition, mutant mice significantly reduced exploratory behavior of ambulation and rearings in a new environment. These results indicate that through H1R, histamine is involved in circadian rhythm buy sinequan of locomotor activity and exploratory behavior as a neurotransmitter.

sinequan drug 2015-08-01

The concepts of depression and hostility are reviewed. The relationship between the two has been clarified by the use of psychometric tests. Hostility levels are high in depressive illness, especially on the intropunitive scales. Both total hostility and the degree of intropunitiveness are reduced as the patient recovers from his illness. Suicidal acts are seen as aggression directed towards the self. In some patients a tendency to recurrent drug overdosage or other forms of self-punitive behaviour may be the result of pathological character traits caused in turn by abnormal development in infancy. Looking at the possibility of cutting down the incidence of suicidal behaviour we conclude that we must look at the influence of depression, total hostility and direction of hostility in precipitating self-damaging acts. It is possible that antidepressants vary in the extent to which they act on these various factors, as well as having different rates of action on the several components of the depressive syndrome. There are thus a priori grounds for predicting that the incidence of self-damaging behaviour will vary from drug to drug. We describe the results of Micronase Tablets a study of suicidal behaviour carried out in general practice. A differential association with the major antidepressant drug was observed. In particular low rates were seen with the imipramine group, and there was a tendency towards high rates with the dothiepin-doxepin group. We propose to investigate this relationship further.

sinequan overdose 2016-01-17

To critically review the body of clinical trials refuting or supporting the efficacy of topical antihistamines in the Moduretic Drug relief of pruritus.

sinequan drug interactions 2015-10-30

A high-performance liquid chromatographic method has been developed for the forensic analysis of eleven frequently used cyclic antidepressant drugs (ADSs) (amitriptyline, amoxapine, clomipramine, desipramine, dosulepine, doxepin, imipramine, maprotiline, melitracen, mianserine and nortriptyline) using a recently developed reversed-phase column with 2 microm particles for the analysis of biological samples. The separation was carried out using two different C8 reversed-phase columns (column 1: 100 mm X 4.6 mm I.D., particle size 2 microm, TSK gel Super-Octyl; column 2: 100 mm X 4.6 mm I.D., particle size 5 microm, Hypersil MOS-C8) for comparison. The mobile phase was composed of methanol-20 mM KH2PO4 (pH 7) (60:40, v/v) and the flow-rate was 0.6 ml/min for both columns. The absorbance of the eluent was monitored at 254 nm. When the eleven drugs were determined, the sensitivity with the 2 microm particles was about five times greater than with the 5 microm particles. Retention times on column 1 were shorter than those on column 2. These results show that the new ODS column packing with a particle size of 2 microm gives higher Ventolin Medication sensitivity and a shorter analysis time than the conventional ODS column packing when applied to the analysis of biological samples.

sinequan capsule 2016-10-31

The authors Nexium 5 Mg conducted a computerized search of MEDLINE for articles. The review includes studies in which serum levels of drugs were obtained from nursing infants.

buy sinequan online 2016-04-29

No clinically significant irritant or sensitization reactions were associated with applications of topical formulations containing clobetasol propionate, doxepin hydrochloride, metronidazole, mupirocin, oxiconazole nitrate, and terbinafine hydrochloride. The doxepin hydrochloride cream vehicle was also found to be nonirritating and nonsensitizing. Both calcipotriene and ketoconazole were moderate irritants and possible sensitization reactions Cymbalta Pill Description were also associated with ketoconazole.

sinequan drug test 2017-05-04

This review will focus specifically on CYP2D6 genetic polymorphisms and their relevance for poisoning due to amfetamines, opioid analgesics and antidepressants in humans Zithromax Dose Chart .

sinequan 75 mg 2016-11-12

Antihistamines are efficacious drugs to be used for the symptomatic relief of allergic diseases. The safety issue of antihistamines is of central importance because of their widespread use in current medical practice. To better understand the pharmacological effects of antihistamines on the central nervous system (CNS), we used two kinds of new methods, positron emission tomography (PET) and gene targeting regarding on histamine H1 receptors. The histamine H1 receptor occupancy was examined in young male volunteers with[11C]-doxepin (a potent H1 antagonist) after the oral or intravenous administration of antihistamines. In other studies, the cognitive performance was also measured tachistoscopically before and after taking antihistamines. The mutant mice lacking H1 receptors were used in the behavioural and neurochemical experiments to re-evaluate the role of H1 receptors. The H1-receptor occupancy in the human frontal cortex caused by antihistamines is significantly correlated with the reported values of incidence of sleepiness in clinical trials, and the occupancy is well proportional to the impaired cognitive performance. The behavioural studies of the H1-receptor knock-out mice confirmed the role of H1 receptors in arousal, the sleep-wake cycle, locomotion, nociception and aggressive behaviour. The pharmacological effects induced by H1 antagonism were re-evaluated by the PET and gene-targetting. Although any serious effects could not be Omnicef 200 Mg observed in mice by the destruction of the H1-receptor gene, the cognitive performance was impaired in humans after taking first generation antihistamines in recommended doses.

sinequan 150 mg 2016-10-16

A variety of antidepressants of different chemical classes were tested for their in vivo and in vitro activity at 5-HT1C receptors in the brain Amoxil Suspension Dosing . Conventional tricyclic antidepressants (imipramine, desipramine, maprotiline, clomipramine, trimipramine, amitriptyline, nortriptyline, doxepin, amoxapine) as well as mianserin and trazodone were found to display high to low nanomolar affinity for 5-HT1C receptors. Antidepressants of other chemical classes and with other mechanisms of action (affecting amine uptake systems: fluoxetine, citalopram, sertraline, fluvoxamine, nomifensine, amineptine; or monoamine oxidase inhibitors: moclobemide, iproniazid) had negligible affinities (micromolar range) for 5-HT1C receptors, except fluoxetine. When tested in an in vivo rat model thought to reveal functional agonistic or antagonistic properties at 5-HT1C receptors, all antidepressants displaying high affinity for this receptor type (except clomipramine and trimipramine) were antagonists at 5-HT1C receptors. Antidepressants with a lower affinity for 5-HT1C receptors (except nomifensine) were inactive in this functional in vivo model. Taken together, these results suggest that antagonism at brain 5-HT1C receptors is a component of the antiserotonergic properties of a number of established antidepressants. In addition, the study confirmed that 5-HT1A receptors functionally interact with 5-HT1C receptors, which suggests that some degree of activity at 5-HT1A receptors may also be an important property for antidepressant activity.

sinequan drug classification 2017-04-03

A questionnaire was distributed Canada-wide to allergists, dermatologists, and a selection of practitioners with an interest in alternative medicine. The survey included questions on demographics, epidemiology, causative factors, diagnostic methods, therapeutic strategies, follow-up advice, and efficacy of therapies, with emphasis on personal experience.