5-HT_1A Receptor ( IC50 = 450 nM ); 5-HT_1B Receptor ( IC50 = 40 nM ); 5-HT_2A Receptor ( IC50 = 4 nM ); 5-HT_2B Receptor ( IC50 = 40 nM );
5-HT_2C Receptor ( IC50 = 6 nM ); H₁ Receptor ( IC50 = 1.1 nM ); H₃ Receptor ( IC50 = 1 μM ); H₄ Receptor ( IC50 = 33.6 nM );
SERT ( Ki = 3.45 nM ); NET ( Ki = 13.3 nM ); DAT ( Ki = 2.58 μM ); Adrenergic receptor ( IC50 = 24 nM ); muscarinic receptor ( IC50 = 7.2 nM ); TrkA; TrkB

体外活性：阿米替林在完整 CHO/DOR 细胞中抑制毛喉素刺激的环 AMP 积累，EC50 值为 16.2 μM。阿米替林对 CHO/DOR 细胞中的 ERK1/2 和 GSK-3β 磷酸化产生浓度依赖性刺激，EC50 值为 9.0 μM。阿米替林 (15 μM) 会刺激 C6 细胞中的 ERK1/2 磷酸化。阿米替林 (30 μM) 抑制毛喉素刺激的腺苷酸环化酶活性并拮抗大鼠伏隔核中的 (−)-U50,488 抑制作用。阿米替林结合 TrkA 和 TrkB 的胞外结构域并促进 TrkA-TrkB 受体异二聚化。阿米替林 (< 500 nM) 促进原代神经元中的 TrkA 自磷酸化，并诱导 PC12 细胞中的神经突生长。阿米替林选择性保护 T17 细胞免于凋亡，EC50 为 50 nM。

阿米替林（15 mg/kg，腹腔注射）可激活 TrkA 和 TrkB 受体，并显着减少小鼠红藻氨酸触发的神经元细胞死亡。阿米替林（15 mg/kg 和 30 mg/kg，腹腔注射）剂量依赖性地减少小鼠强迫游泳试验（FST）中的不动时间。阿米替林（15 mg/kg，腹腔注射）在小鼠强迫游泳试验（FST）中显示出显着的 24 小时不动时间节律。阿米替林（1 mg/kg 和 3 mg/kg）显着增加了小鼠在新型笼子中的总移动距离。阿米替林（10 mg/kg，口服，每日两次）可显着减弱小鼠对 8-OHDPAT 和 mCPP 的低温反应。阿米替林（10 mg/kg，口服，每日两次）显着降低小鼠皮质中的血清素转运蛋白密度约 20%。

细胞系：海马神经元
浓度：0.5 μM
孵育时间：30 分钟
结果：诱导 TrkA 磷酸化。诱导 Erk 1/2 和 Akt 信号传导激活。

Absorption, Distribution and Excretion
Rapidly absorbed following oral administration (bioavailability is 30-60% due to first pass metabolism). Peak plasma concentrations are reached 2-12 hours after oral or intramuscular administration. Steady-state plasma concentrations vary greatly and this variation may be due to genetic differences.
Amitriptyline and its metabolites are mainly excreted in the urine. Virtually the entire dose is excreted as glucuronide or sulfate conjugate of metabolites, with approximately 2% of unchanged drug appearing in the urine. 25-50% of a single orally administered dose is excreted in urine as inactive metabolites within 24 hours. Small amounts are excreted in feces via biliary elimination.
The apparent volume of distribution (Vd)β estimated after intravenous administration is 1221 L±280 L; range 769-1702 L (16±3 L/kg). It is found widely distributed throughout the body. Amitriptyline and the main metabolite _nortriptyline_ pass across the placental barrier and small amounts are present in breast milk.
The mean systemic clearance (Cls) is 39.24 ± 10.18 L/h (range: 24.53-53.73 L/h). No clear effect of older age on the pharmacokinetics of amitriptyline has been determined, although it is possible that clearance may be decreased.
This study reports the pharmacokinetics of oral amitriptyline and its active metabolite nortriptyline in Greyhound dogs. Five healthy Greyhound dogs were enrolled in a randomized crossover design. A single oral dose of amitriptyline hydrochloride (actual mean dose 8.1 per kg) was administered to fasted or fed dogs. Blood samples were collected at predetermined times from 0 to 24 hr after administration, and plasma drug concentrations were measured by liquid chromatography with mass spectrometry. Noncompartmental pharmacokinetic analyses were performed. Two dogs in the fasted group vomited following amitriptyline administration and were excluded from analysis. The range of amitriptyline CMAX for the remaining fasted dogs (n = 3) was 22.8-64.5 ng/mL compared to 30.6-127 ng/mL for the fed dogs (n = 5). The range of the amitriptyline AUCINF for the three fasted dogs was 167-720 hr ng/mL compared to 287-1146 hr ng/mL for fed dogs. The relative bioavailability of amitriptyline in fasted dogs compared to fed dogs was 69-91% (n = 3). The exposure of the active metabolite nortriptyline was correlated to amitriptyline exposure (R(2) = 0.84). Due to pharmacokinetic variability and the small number of dogs completing this study, further studies are needed assessing the impact of feeding on oral amitriptyline pharmacokinetics. Amitriptyline may be more likely to cause vomiting in fasted dogs.
The inability of a 30-yr-old female with graft-versus-host disease to absorb oral doses of amitriptyline was reported. Only trace plasma levels of the drug were determined following 4 wk therapy with 50 mg daily doses. Additional therapy with 75 mg daily doses for 10 days failed to incr the antidepressant's plasma levels.
An experimental rat model was used to study postmortem redistribution of amitriptyline. Two hr after a sc injection with 20 mg of amitriptyline, the rats (n=40) were anesthetized and blood samples were drawn from the femoral vein and the heart. The rats were then sacrificed by CO2 and left at room temp for either 0.1, 1, 2, 5, 24, 48, or 96 hr. Postmortem blood samples from the heart and the inferior vena cava, and tissue samples from the lungs, heart, liver, right kidney, thigh muscle, the wall of the abdominal vena cava and brain were analyzed by HPLC. A significant incr was observed within 2 hr postmortem in heart blood and later also in blood from the inferior vena cava. At 96 hr postmortem the concn incr was 4.4 + or - 0.5-fold (p < 0.01) and 3.0 + or - 1.1-fold (p < 0.05) as compared to the antemortem values observed in heart blood and blood from the inferior vena cava, respectively (mean + or - SEM). In the lungs there was a fall in the concn of AMI from 148 + or - 16.7 umol/kg at 0.1 hr to 49.1 + or - 7.8 umol/kg at 96 hr postmortem (p < 0.01). In the vessel wall of the abdominal vena cava there was also a significant fall in drug concn, while in heart muscle and liver an incr in drug concn was observed. In animals where the lungs were removed agonally (n = 7), the drug concn in heart blood had incr significantly less at 2 hr postmortem.
The percutaneous absorption of amitriptyline, nortriptyline, imipramine, and desipramine as their hydrochloride salts in vivo was demonstrated without use of a vehicle using the hairless (hr-1/hr-1) mouse as an experimental model for human skin. After topical application of 2 mg of each compound in distilled water, followed by rapid evaporation of the water, concn were measured in heart, lung, brain, liver, and blood in 1-, 2-, 4-, and 6-hr study groups. Lung consistently demonstrated the highest concn for all four compounds while heart and liver had the lowest. Concn in heart remained essentially constant for all compounds during the 6-hour study period. The concn in solid tissues were much lower than those commonly seen in man after overdose, whereas the concn in blood resembled low therapeutic to toxic concn in humans. Percutaneous absorption may provide a feasible route of admin for the tricyclic antidepressants which may lead to improved compliance with fewer GI side effects. /Amitriptyline hydrochloride/
For more Absorption, Distribution and Excretion (Complete) data for AMITRIPTYLINE (17 total), please visit the HSDB record page.

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Metabolism / Metabolites
In vitro, the metabolism of amitriptyline occurs mainly by demethylation (CYP2C19, CYP3A4) as well as hydroxylation (CYP2D6) followed by conjugation with glucuronic acid. Other isozymes involved in amitriptyline metabolism are CYP1A2 and CYP2C9. The metabolism of this drug is subject to genetic polymorphisms. The main active metabolite is the secondary amine, _nortriptyline_. Nortriptyline is a stronger inhibitor of noradrenaline than of serotonin uptake, while amitriptyline inhibits the uptake of noradrenaline and serotonin with equal efficacy. Other metabolites such as _cis-_ and _trans-10-hydroxyamitriptyline_ and _cis-_ and _trans-10-hydroxynortriptyline_ have the same pharmacologic profile as nortriptyline but are significantly weaker. _Demethylnortriptyline_ and amitriptyline N oxide are only present in plasma in negligible amounts; the latter is mostly inactive.
A method for the determination of amitriptyline and some of its metabolites in serum on a reversed phase system consisting of C-8 bonded phase material as the stationary phase and water-methanol-dichloromethane-propylamine as the mobile phase by liquid chromatography with UV detection at 254 nm is described. ... Serum levels of amitriptyline and its 4 main metabolites (nortriptyline, desmethylnortriptyline, trans-10-hydroxyamitriptyline and trans-10-hydroxynortriptyline) in a patient receiving 150 mg of oral amitriptyline daily are reported.
Amitriptyline is metabolized via the same pathways as are other tricyclic antidepressants; nortriptyline, its N-monodemethylated metabolite, is pharmacologically active.
To investigate the metabolism of amitriptyline and debrisoquine ... 8 healthy Chinese volunteers received a single oral dose of 100 mg amitriptyline and the ratios between the area under the curve (AUC) of amitriptyline and its 3 metabolites were evaluated. Results indicated that large interindividual differences in AUC were observed. In addition, hydroxylation of amitriptyline and debrisoquine may be regulated by similar enzymatic processes.
Biotransformation of amitriptyline to its demethylated product nortriptyline was studied in vitro with human liver microsomes from four different donors, preselected to reflect a range of metabolic rates. Reaction velocity versus substrate concn was consistent with a sigmoid Vmax model. Vmax varied from 0.42 to 3.42 nmol/mg/min, Km from 33 to 89 uM amitriptyline. Ketoconazole was a highly potent inhibitor of N-demethylation, with a mean Ki value of 0.11 + or - 0.013 uM ... whereas quinidine (up to 50 uM), a CYP2D6 inhibitor, and alpha-naphthoflavone (up to 5 uM), a CYP1A2 inhibitor only at low concn, showed no effect. All selective serotonin reuptake inhibitors tested had an inhibitory effect on the formation of nortriptyline, with mean Ki values of 4.37 (+ or - 3.38) uM for sertraline, 5.46 (+ or - 1.95) uM for desmethylsertraline, 9.22 (+ or - 3.69) uM for fluvoxamine, 12.26 (+ or - 5.67) uM for norfluoxetine, 15.76 (+ or - 5.50) uM for paroxetine, and 43.55 (+ or - 18.28) uM for fluoxetine. A polyclonal rabbit antibody against rat liver CYP3A1, in antibody/microsomal protein rations varying from 1:1 to 10:1, inhibited N-demethylation of amitriptyline to an asymptotic max of 60%.
For more Metabolism/Metabolites (Complete) data for AMITRIPTYLINE (8 total), please visit the HSDB record page.
Amitriptyline has known human metabolites that include nortriptyline and E-10-hydroxyamitriptyline.
Amitriptyline is rapidly and well absorbed following oral administration. Exclusively hepatic, with first pass effect. Amitriptyline is demethylated in the liver to its primary active metabolite, nortriptyline.
Route of Elimination: Virtually the entire dose is excreted as glucuronide or sulfate conjugate of metabolites, with little unchanged drug appearing in the urine. 25-50% of a single orally administered dose is excreted in urine as inactive metabolites within 24 hours. Small amounts are excreted in feces via biliary elimination.
Half Life: 10 to 50 hours, with an average of 15 hours

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Biological Half-Life
The elimination half-life (t1⁄2 β) amitriptyline after peroral administration is about 25 hours (24.65 ± 6.31 hours; range 16.49-40.36 hours).
The plasma half-life of amitriptyline ranges from 10 to 50 hours.
The toxicokinetics of amitriptyline were studied in nine patients admitted to hospital in Matthew-Lawson Coma Scale grade III-IV after an estimated ingestion of 1-5 g amitriptyline. ... The T1/2 alpha and T1/2 beta for amitriptyline were 1.5 - 3.1 and 15 - 43 hr respectively. ...
... The purpose of this pilot study was to describe the individual and population pharmacokinetic parameters of amitriptyline after a single oral dose at 1.5 mg/kg, 4.5 mg/kg, and 9 mg/kg in healthy African grey parrots ( Psittacus erithacus , n = 3) and cockatoos (Cacatua species, n = 3). Three birds received an initial 1.5 mg/kg oral dose, and blood samples were collected for 24 hours at fixed time intervals. Serum concentrations of amitriptyline and its metabolites were determined by polarized immunofluorescence. After determining the initial parameters and a 14-day washout period, 2 African grey parrots and 1 cockatoo received a single oral dose at 4.5 mg/kg, and 3 cockatoos and 1 African grey parrot received a single oral dose at 9 mg/kg. ... Elimination half-life varied from 1.6 to 91.2 hours. ...

Toxicity Summary
IDENTIFICATION AND USE: Amitriptyline is in the form of crystals. It is a tricyclic antidepressant. HUMAN EXPOSURE AND TOXICITY: Symptoms of overdose/poisoning may include the following: hypothermia, respiratory depression, seizures, abnormal tendon reflexes, disorientation, agitation, myoclonic jerks, coma, pyramidal signs, arrhythmias, bundle branch block, cardiac arrest, hypotension, circulatory collapse, mydriasis, blurred vision, tachycardia, vasodilation, urinary retention, decreased gastrointestinal motility, decreased bronchial secretions, and dry mucous membranes and skin. A study on children showed that initial symptoms and signs of acute amitriptyline intoxication appeared severe, but they disappeared with only supportive care required in most children except for cases that ingested high doses of drug within a few days. However, antidepressants have been shown to increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. An experiment with amitriptyline demonstrated that antidepressants reduce the release of non-neuronal acetylcholine in the human placenta, but only at concentrations roughly 30-fold above the therapeutic range. Antidepressant therapy of pregnant women should still be done with caution. Amitriptyline HCl was evaluated for its genotoxicity. The evaluation was performed in somatic (bone marrow) and germ (spermatocytes) cells, as well as the sperm morphology (i.e., head and tail) and count of the resulting sperm. The results showed that the treatment induced structural and numerical chromosome abnormalities in somatic cells (bone marrow) and germ cells (spermatocytes). Moreover, the drug significantly reduced both the mitotic index and meiotic activity after the different treatments used. Amitriptyline was found to increase significantly the incidence of sperm-cell head and tail abnormalities. The sperm-cell count was also significantly decreased. These results showed that the effect of the drug was dose dependent. In another study, amitriptyline was found to be nongenotoxic at plasma levels. However, frequencies of chromosome aberrations and sister chromatid exchanges were significantly increased at concentrations 4 and 40 times the plasma level. ANIMAL STUDIES: Symptoms of exposure in dogs include lethargy, tachycardia, vomiting, and hyperthermia. Symptoms in cats have included mydriasis and/or tachycardia, ataxia, lethargy, disorientation, and vomiting. In mice, amitriptyline produces rapid but reversible clouding of the lens, if the eyes are allowed to remain open and unprotected from evaporation. In a study on dogs, oral doses of 20 and 40 mg/kg/day were tolerated for 6 months without hematologic, biochemical or anatomical evidence of drug toxicity. Oral doses of 80 mg/kg/day were not well tolerated: 2 of 4 dogs died within 3 weeks after exhibiting severe ataxia and sedation. Doses of 100 mg/kg/day or greater were not tolerated for more than a few days. Offspring of amitriptyline-treated rats showed reduced locomotor activity. In rats, an oral dose of 25 mg/kg/day (8 times the maximum recommended human dose) produced delays in ossification of fetal vertebral bodies. In rabbits, an oral dose of 60 mg/kg/day (20 times the maximum recommended human dose) was reported to cause incomplete ossification of cranial bones. Amitriptyline was tested for genotoxicity using the somatic mutation and recombination test (SMART) in wing cells of Drosophila melanogaster. The drug was not genotoxic at concentrations up to 100 mM.
Amitriptyline is metabolized to nortriptyline which inhibits the reuptake of norepinephrine and serotonin almost equally. Amitriptyline inhibits the membrane pump mechanism responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons. Pharmacologically this action may potentiate or prolong neuronal activity since reuptake of these biogenic amines is important physiologically in terminating transmitting activity. This interference with the reuptake of norepinephrine and/or serotonin is believed by some to underlie the antidepressant activity of amitriptyline.

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Toxicity Data
LD50: 350 mg/kg (Oral, Mouse) (A308)

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Interactions
The teratogenic potential of a combination of chlordiazepoxide (Cdz) and amitriptyline (Amt) was examined with regard to both internal and external anomalies. Timed pregnant golden hamsters were given a single intraperitoneal injection on day 8 of gestation of one of the following: chlordiazepoxide hydrochloride (28.5 mg/kg), amitriptyline hydrochloride (70.3 mg/kg), Cdz-Amt combination (28.5 mg/kg Cdz + 70.3 mg/kg Amt, in order to retain the 1:2.5 dose ratio utilized in a clinically-used preparation of these agents), or saline vehicle (control). Fetuses were recovered on gestation day 15 following maternal sacrifice. Cranial malformations were analyzed in Bouin's-fixed fetuses by making 1-mm coronal sections through each head, whereas visceral anomalies were examined following general dissection of each body. Amt alone produced a significant (P less than 0.05) incidence of bent tail and encephalocele, whereas Cdz significantly (P less than 0.05) altered the male:female ratio of surviving fetuses when compared with saline-injected controls. The Cdz-Amt combination caused significant increases in cranial malformations, open eye, bent tail, abnormal lung, and urogenital anomalies. The teratogenic effects of potentiation between the components of this combination are discussed in terms of external and internal malformations.
Caution is advised if patients receive large doses of ethchlorvynol concurrently. Transient delirium has been reported in patients who were treated with one gram of ethchlorvynol and 75 to 150 mg of amitriptyline hydrochloride.
The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7 to 10% of Caucasians are so called "poor metabolizers"); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be coadministered with another drug known to be an inhibitor of P450 2D6. /Tricyclic antidepressants/
The combination (ethanol and amitriptyline) produced greater impairment of 3 psychomotor functions in animals than did either drug alone. Ethanol pretreatment also produced A 2.23% increase in the total tricyclic antidepressant brain concentration.
For more Interactions (Complete) data for AMITRIPTYLINE (33 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Mouse iv 16 mg/kg
LD50 Mouse sc 140 mg/kg
LD50 Mouse ip 56 mg/kg
LD50 Mouse oral 140 mg/kg
For more Non-Human Toxicity Values (Complete) data for AMITRIPTYLINE (6 total), please visit the HSDB record page.

[1]. Biol Psychiatry . 2004 Feb 1;55(3):320-2.

[2]. Mol Pharmacol . 2001 Mar;59(3):427-33.

[3]. J Pharmacol Exp Ther . 2001 Oct;299(1):83-9.

[4]. Exp Neurol . 2007 Oct;207(2):248-57.

[5]. J Pharmacol Exp Ther . 2010 Jan;332(1):255-65.

[6]. Chem Biol . 2009 Jun 26;16(6):644-56.

[7]. J Pharmacol Exp Ther . 2005 Nov;315(2):764-70.

[8]. Psychopharmacology (Berl) . 2005 Oct;181(4):741-50.

[9]. Bioorg Med Chem . 2006 Oct 1;14(19):6640-58.

Therapeutic Uses
Adrenergic Uptake Inhibitors; Analgesics, Non-Narcotic; Antidepressive Agents, Tricyclic
/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Amitriptyline is included in the database.
For the relief of symptoms of depression. Endogenous depression is more likely to be alleviated than are other depressive states. /Included in US product labeling/
Tricyclic antidepressants have been used for the treatment of attention deficit hyperactivity disorder (ADHD). /Tricyclic antidepressant; NOT included in US product label/
For more Therapeutic Uses (Complete) data for AMITRIPTYLINE (13 total), please visit the HSDB record page.

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Drug Warnings
/BOXED WARNING/ Suicidality and Antidepressant Drugs: Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of amitriptyline hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Amitriptyline hydrochloride is not approved for use in pediatric patients.
A syndrome resembling neuroleptic malignant syndrome (NMS) has been very rarely reported after starting or increasing the dose of amitriptyline hydrochloride, with and without concomitant medications known to cause NMS. Symptoms have included muscle rigidity, fever, mental status changes, diaphoresis, tachycardia, and tremor.
Very rare cases of serotonin syndrome (SS) have been reported with amitriptyline hydrochloride in combination with other drugs that have a recognized association with SS.
Amitriptyline hydrochloride ... should be used with caution in patients with a history of seizures and, because of its atropine-like action, in patients with a history of urinary retention, angle-closure glaucoma or increased intraocular pressure. In patients with angle-closure glaucoma, even average doses may precipitate an attack.
For more Drug Warnings (Complete) data for AMITRIPTYLINE (39 total), please visit the HSDB record page.

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Pharmacodynamics
**Effects in pain and depression** Amitriptyline is a tricyclic antidepressant and an analgesic. It has anticholinergic and sedative properties. Clinical studies have shown that oral amitriptyline achieves, at a minimum, good to moderate response in up to 2/3 of patients diagnosed with post-herpetic neuralgia and 3/4 of patients diagnosed with diabetic neuropathic pain, and neurogenic pain syndromes that are frequently unresponsive to narcotic analgesics. Amitriptyline has also shown efficacy in diverse groups of patients with chronic non-malignant pain. There have also been some studies showing efficacy in managing fibromyalgia (an off-label use of this drug),. **Cardiovascular and Anticholinergic Effects** Amitriptyline has strong anticholinergic properties and may cause ECG changes and quinidine-like effects on the heart. Amitriptyline may inhibit ion channels, which are necessary for cardiac repolarization (hERG channels), in the upper micromolar range of therapeutic plasma concentrations. Therefore, amitriptyline may increase the risk for cardiac arrhythmia. Orthostatic hypotension and tachycardia can be a problem in elderly patients receiving this drug at normal doses for depression. There is evidence in the literature that these effects may occur, rarely, at the lower dosages utilized in the treatment of pain. As with any other tricyclic antidepressant agent, increased glucose levels can occur with amitriptyline. **Effects on seizure threshold** This drug also decreases the convulsive threshold and causes alterations in EEG and sleep patterns.

C20H24CLN

313.86

313.159

C, 76.54; H, 7.71; Cl, 11.29; N, 4.46

549-18-8

Amitriptyline-d3 hydrochloride; 342611-00-1; Amitriptyline-d6 hydrochloride; 203645-63-0; Amitriptyline; 50-48-6

2160

White to off-white solid powder

1.076g/cm3

398.2ºC at 760 mmHg

196-197°C

11 °C

4.97

3.24

0

1

3

21

331

0

Cl[H].N(C([H])([H])[H])(C([H])([H])[H])C([H])([H])C([H])([H])/C(/[H])=C1/C2=C([H])C([H])=C([H])C([H])=C2C([H])([H])C([H])([H])C2=C([H])C([H])=C([H])C([H])=C/12

KFYRPLNVJVHZGT-UHFFFAOYSA-N

InChI=1S/C20H23N.ClH/c1-21(2)15-7-12-20-18-10-5-3-8-16(18)13-14-17-9-4-6-11-19(17)20;/h3-6,8-12H,7,13-15H2,1-2H3;1H

N,N-dimethyl-3-(2-tricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,11,13-hexaenylidene)propan-1-amine;hydrochloride

trade names: Elavil; Amitriptylin; Tryptanol; Damilen; Triptanol; Amitriptyline HCl; Amitriptyline hydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: 120 mg/mL (382.34 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶。

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配方 2 中的溶解度: 5%DMSO + Corn oil: 4.0mg/ml (12.74mM)

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。