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Amitriptyline, formerly sold under the brand name Elavil among others, is a tricyclic antidepressant primarily used to treat major depressive disorder, and a variety of pain syndromes such as neuropathic pain, fibromyalgia, migraine and tension headaches.[11] Due to the frequency and prominence of side effects, amitriptyline is generally considered a second-line therapy for these indications.[12][13][14][15]
The most common side effects are dry mouth, drowsiness, dizziness, constipation, and weight gain. Glaucoma, liver toxicity and abnormal heart rhythms are rare but serious side effects. Blood levels of amitriptyline vary significantly from one person to another,[16] and amitriptyline interacts with many other medications potentially aggravating its side effects.
Amitriptyline was discovered in the late 1950s by scientists at Merck and approved by the US Food and Drug Administration (FDA) in 1961.[17] It is on the World Health Organization’s List of Essential Medicines.[18] It is available as a generic medication.[19] In 2023, it was the 90th most commonly prescribed medication in the United States, with more than 7 million prescriptions.[20][21]
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Medical uses
Amitriptyline is indicated for the treatment of major depressive disorder, neuropathic pain, and for the prevention of migraine and chronic tension headache. It can be used for the treatment of nocturnal enuresis in children older than 6 after other treatments have failed.[11]
Depression
Amitriptyline is effective for depression,[22] but it is rarely used as a first-line antidepressant due to its higher toxicity in overdose and generally poorer tolerability.[23] It can be tried for depression as a second-line therapy, after the failure of other treatments.[12] For treatment-resistant adolescent depression[24] or for cancer-related depression[25] amitriptyline is no better than placebo; however, the number of treated patients in both studies was small. It is sometimes used for the treatment of depression in Parkinson’s disease,[26] but supporting evidence for its effectiveness in that respect is lacking.[27]
Pain
Amitriptyline alleviates painful diabetic neuropathy. It is recommended by a variety of guidelines as a first or second-line treatment.[13] It is as effective for this indication as gabapentin or pregabalin but less well tolerated.[28] Amitriptyline is as effective at relieving pain as duloxetine. Combination treatment of amitriptyline and pregabalin offers additional pain relief for people whose pain is not adequately controlled with one medication and is usually safe.[29][30] Amitriptyline in certain formulations may also induce the level of sciatic-nerve blockade needed for local anesthesia therein.[31] Here, it has been demonstrated to be of superior potency to bupivacaine, a customary long-acting local anesthetic.
Low doses of amitriptyline moderately improve sleep disturbances and reduce pain and fatigue associated with fibromyalgia.[32] It is recommended for fibromyalgia accompanied by depression by Association of the Scientific Medical Societies in Germany[32] and as a second-line option for fibromyalgia, with exercise being the first line option, by European League Against Rheumatism.[14] Combinations of amitriptyline and fluoxetine or melatonin may reduce fibromyalgia pain better than either medication alone.[33]
There is some (low-quality) evidence that amitriptyline may reduce pain in cancer patients. It is recommended only as a second-line therapy for non-chemotherapy-induced neuropathic or mixed neuropathic pain if opioids did not provide the desired effect.
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| Propane Dacthal Dimethyl carbonate Dimethyl sulfate Dimethyl fumarate Dimethyl ether Dimethyl phthalate Dimethyl sulfoxide N,N-Dimethylformamide Ethane Amitriptyline Related Compound A PIROHEPTINE Cotriptyline Amitriptyline hydrochloride (-)-2-[Methylamino]-1-phenylpropane D/L-amphetamine hydrochloride Nortriptyline hydrochloride Cycloheptene | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Amitriptyline
Content Navigation
CAS Number
Product Name
IUPAC Name
Molecular Formula
Molecular Weight
InChI
InChI Key
solubility
In water, 9.71 mg/L at 24 °C
4.50e-03 g/L
Synonyms
Canonical SMILES
Purity
Package Size
Amitriptyline (CAS 50-48-6) is a prototypical tertiary amine tricyclic antidepressant (TCA) and a critical reference material in neuropharmacology, toxicology, and transdermal formulation development. As a free base, it is characterized by its high lipophilicity (log P ~ 4.9) and broad-spectrum receptor binding profile. Unlike newer, highly selective monoamine reuptake inhibitors, amitriptyline functions as a potent, balanced inhibitor of both the serotonin (SERT) and norepinephrine (NET) transporters, while simultaneously exhibiting high-affinity antagonism at histaminergic (H1), muscarinic, and alpha-adrenergic receptors. In procurement contexts, the free base form is specifically sought after for non-aqueous formulations, topical analgesic patches, and receptor binding assays where salt dissociation kinetics or aqueous solubility constraints would introduce experimental artifacts or formulation barriers[1].
Research Fit
Substituting amitriptyline free base with its hydrochloride salt (CAS 549-18-8) or closely related TCA analogs fundamentally alters both processability and pharmacological behavior. In formulation workflows, the HCl salt exhibits poor partitioning into lipophilic vehicles (like isopropyl myristate or propylene glycol) and significantly lower transdermal flux, often requiring chemical conversion back to the free base to achieve viable topical delivery [1]. Pharmacologically, substituting amitriptyline with its primary active metabolite, nortriptyline (a secondary amine), shifts the transporter inhibition ratio drastically toward NET selectivity, ruining its utility as a balanced dual-reuptake benchmark. Similarly, substituting with desipramine eliminates the high-affinity H1 and muscarinic binding that makes amitriptyline the industry-standard positive control for off-target sedative and anticholinergic liability screening [2].
Substitution Risk
Free Base vs. Hydrochloride Salt in Transdermal Formulations
For topical analgesic applications, the physical form of amitriptyline dictates formulation success. Amitriptyline free base demonstrates exceptional solubility in lipophilic penetration enhancers (e.g., >1000 mg/mL in propylene glycol at 32°C), enabling direct incorporation into non-aqueous vehicles like isopropyl myristate/isopropyl alcohol blends. In contrast, amitriptyline hydrochloride requires either complex coacervate systems or in-situ pH adjustment (to pH 9-10) to convert it back to the free base for sufficient stratum corneum partitioning. Studies show that vehicles optimized for the free base yield multi-fold increases in 24-hour skin permeation compared to standard salt formulations[1].
| Evidence Dimension | Lipophilic Vehicle Solubility and Formulation Readiness |
| Target Compound Data | Amitriptyline Free Base: Soluble >1000 mg/mL in propylene glycol; directly compatible with lipophilic transdermal patches. |
| Comparator Or Baseline | Amitriptyline HCl: Poor lipid solubility; requires chemical conversion (pH 9-10) or specialized carrier systems for viable skin flux. |
| Quantified Difference | >1000 mg/mL solubility in PG for free base; eliminates the mandatory conversion step required for the HCl salt. |
| Conditions | In vitro porcine skin permeation studies and solubility assays at 32°C. |
Procuring the free base directly eliminates costly and variable chemical conversion steps during the manufacturing of topical neuropathic pain formulations.
Monoamine Transporter Inhibition: Amitriptyline vs. Nortriptyline
Amitriptyline serves as a critical dual-action benchmark in monoamine research due to its balanced affinity for both key transporters. Quantitative binding assays demonstrate that amitriptyline inhibits the serotonin transporter (SERT) with a Ki of 3.45 nM and the norepinephrine transporter (NET) with a Ki of 13.3 nM. If a researcher or buyer substitutes amitriptyline with its secondary amine metabolite, nortriptyline, the pharmacological profile shifts heavily toward NET selectivity (nortriptyline is approximately 5 times more potent at NET than amitriptyline, while losing SERT affinity). This structural difference makes amitriptyline specifically suited for assays requiring simultaneous, high-affinity blockade of both pathways .
| Evidence Dimension | Transporter Binding Affinity (Ki) |
| Target Compound Data | Amitriptyline: SERT Ki = 3.45 nM; NET Ki = 13.3 nM (Balanced dual inhibition). |
| Comparator Or Baseline | Nortriptyline: Highly NET-selective (approx. 5x more potent at NET than amitriptyline). |
| Quantified Difference | Amitriptyline maintains low-nanomolar affinity across both SERT and NET, whereas nortriptyline is heavily skewed toward NET. |
| Conditions | In vitro radioligand binding assays for human monoamine transporters. |
Amitriptyline is the strictly required reference standard when validating novel balanced Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs), as secondary amine TCAs fail to provide the necessary dual-inhibition baseline.
Off-Target Binding: Amitriptyline vs. Desipramine
In safety pharmacology and toxicology, amitriptyline is utilized as a definitive positive control for off-target central nervous system (CNS) depression and weight-gain liabilities, driven primarily by its extreme affinity for the histamine H1 receptor. Amitriptyline binds to the H1 receptor with a Ki of 0.5 to 4.0 nM, making it one of the most potent H1 antagonists among all psychotropic drugs. In contrast, other TCAs like desipramine exhibit much weaker H1 affinity (Ki ~ 26 nM or higher) and significantly lower muscarinic affinity. Consequently, amitriptyline produces a robust, reproducible sedative and anticholinergic signal in phenotypic and binding assays that cannot be reliably replicated by substituting lower-affinity analogs [1].
| Evidence Dimension | Histamine H1 Receptor Binding Affinity (Ki) |
| Target Compound Data | Amitriptyline: H1 Ki = 0.5 – 4.0 nM (Extreme high affinity). |
| Comparator Or Baseline | Desipramine: H1 Ki = 26 nM (Low affinity). |
| Quantified Difference | Amitriptyline exhibits roughly 6- to 50-fold greater binding affinity for the H1 receptor compared to desipramine. |
| Conditions | Radioligand competition binding assays in mammalian brain membranes. |
Procuring amitriptyline provides an indispensable, high-potency positive control for screening out unwanted sedative and antihistaminic off-target effects in new CNS drug candidates.
Transdermal and Topical Analgesic Formulation
Because amitriptyline free base exhibits greater lipophilicity and stratum corneum partitioning compared to its hydrochloride salt, it is the selected active pharmaceutical ingredient (API) for developing non-aqueous topical formulations. It is specifically utilized in the R&D and manufacturing of transdermal patches and lipophilic gels (e.g., propylene glycol or isopropyl myristate vehicles) targeting peripheral neuropathic pain, where bypassing first-pass metabolism and maximizing local skin flux is critical [1].
Dual SERT/NET Inhibition Reference Standard
Due to its balanced, low-nanomolar affinity for both the serotonin (Ki = 3.45 nM) and norepinephrine (Ki = 13.3 nM) transporters, amitriptyline is an essential baseline comparator in high-throughput screening (HTS) workflows. It is used by medicinal chemists and pharmacologists to benchmark the efficacy and selectivity of novel Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) and next-generation antidepressants, a role that secondary amine TCAs cannot fulfill .
Positive Control for Safety Pharmacology & Toxicology
Amitriptyline’s exceptionally high affinity for histamine H1 (Ki = 0.5 – 4.0 nM) and muscarinic receptors makes it a standard positive control in off-target liability screening. Toxicology labs procure amitriptyline to calibrate in vitro binding assays and in vivo phenotypic models designed to detect unwanted sedative, anticholinergic, and cardiotoxic side effects in early-stage CNS drug candidates [2].
Application Fit Matrix
Physical Description
Color/Form
XLogP3
Hydrogen Bond Acceptor Count
Exact Mass
Monoisotopic Mass
Boiling Point
Heavy Atom Count
LogP
4.92 (LogP)
log Kow = 4.92
4.9
Decomposition
Appearance
Melting Point
196 – 197 °C
Storage
UNII
Related CAS
30227-34-0 (maleate (1:1))
549-18-8 (hydrochloride)
GHS Hazard Statements
H301+H311+H331 (80.1%): Toxic if swallowed, in contact with skin or if inhaled [Danger Acute toxicity, oral;
acute toxicity, dermal;
acute toxicity, inhalation];
H302 (19.39%): Harmful if swallowed [Warning Acute toxicity, oral];
H318 (80.1%): Causes serious eye damage [Danger Serious eye damage/eye irritation];
H361 (80.1%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity];
H410 (80.1%): Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard];
Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.
Use and Manufacturing
Drug Indication
Amitriptyline is FDA approved medication to treat major depressive disorder (MDD) in adults. The non-FDA-approved indications include anxiety, post-traumatic stress disorder, insomnia, chronic pain (diabetic neuropathy, fibromyalgia), irritable bowel syndrome, interstitial cystitis (bladder pain syndrome), migraine prophylaxis, postherpetic neuralgia, and sialorrhea. Amitriptyline has been used for post-COVID headaches.
Livertox Summary
Drug Classes
Antidepressant Agents
Therapeutic Uses
/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.
Pharmacology
Amitriptyline is a derivative of dibenzocycloheptadiene and a tricyclic antidepressant. Amitriptyline inhibits the re-uptake of norepinephrine and serotonin by the presynaptic neuronal membrane in the central nervous system (CNS), thereby increasing the synaptic concentration of norepinephrine and serotonin. Due to constant stimulation to these receptors, amitriptyline may produce a downregulation of adrenergic and serotonin receptors, which may contribute to the antidepressant activity.
MeSH Pharmacological Classification
ATC Code
N06 – Psychoanaleptics
N06A – Antidepressants
N06AA – Non-selective monoamine reuptake inhibitors
N06AA09 – Amitriptyline
Mechanism of Action
Acute and chronic effects of the antidepressant drugs tranylcypromine, a monoamine oxidase inhibitor, and amitriptyline, a monoamine uptake inhibitor, were studied on beta-adrenergic receptor function in mouse astrocytes in primary cultures. In clinically relevant concentrations, acute administration of either antidepressant drug had a direct inhibitory effect on the binding of the beta-adrenergic ligand dihydroalprenolol and on the isoproterenol-induced accumulation of cyclic AMP. However, in the absence of isoproterenol, these drugs enhanced the formation of cyclic AMP in the astrocytes. Chronic exposure to amitriptyline or tranylcypromine led to a decrease in isoproterenol-induced accumulation of cyclic AMP, and the time course for the development of this phenomenon was similar to that reported for whole brain in vivo. These findings suggest that these antidepressant drugs act as a partial agonists at beta-adrenergic receptors on astrocytes, and that the down-regulation of beta-adrenergic activity that occurs in vivo after chronic administration of antidepressant drugs may, to a large extent, take place in astrocytes and may result from the partial beta-agonist nature of the drugs.
Astrocytes play important roles in guiding the construction of the nervous system, controlling extracellular ions and neurotransmitters, and regulating CNS synaptogenesis. Egr-1 is a transcription factor involved in neuronal differentiation and astrocyte cell proliferation. In this study, we investigated whether the tricyclic antidepressant (TCA) amitriptyline induces Egr-1 expression in astrocytes using rat C6 glioma cells as a model. We found that amitriptyline increased the expression of Egr-1 in a dose- and time-dependent manner. The amitriptyline-induced Egr-1 expression was mediated through serum response elements (SREs) in the Egr-1 promoter. SREs were activated by the Ets-domain transcription factor Elk-1 through the ERK and JNK mitogen-activated protein (MAP) kinase pathways. The inhibition of the ERK and JNK MAP kinase signals attenuated amitriptyline-induced transactivation of Gal4-Elk-1 and Egr-1 promoter activity. Our findings suggest that the induction of Egr-1 expression in astrocytes may be required to attain the therapeutic effects of antidepressant drugs.
Antidepressants such as serotonin-noradrenaline reuptake inhibitors (SNRIs) and tricyclic antidepressants (TCAs) are frequently used for the management of neuropathic pain. Noradrenaline (NA) and serotonin (5-HT) increase in the spinal cord by reuptake inhibition is considered to be main mechanism of the therapeutic effect of antidepressants in neuropathic pain. In the present study, we examined the analgesic effects of duloxetine (SNRI) and amitriptyline (TCA) in a rat model of neuropathic pain induced by spinal nerve ligation (SNL). Intraperitoneal administration of duloxetine and amitriptyline dose-dependently (3,10 and 30 mg/kg) suppressed hyperalgesia induced by SNL. In vivo microdialysis in the lumbar spinal dorsal horn revealed that NA and 5-HT concentrations increased after intraperitoneal administration of duloxetine and amitriptyline (10 mg/kg, respectively). We further determined NA and 5-HT contents in homogenized samples from the ipsilateral dorsal spinal cord after SNL. Although the NA content in SNL rats 2 weeks after ligation was higher than that in SNL rats 4 weeks after ligation, the analgesic efficacy of duloxetine and amitriptyline was similar between two groups. The present study suggests that NA/5-HT increase in the spinal cord is crucial in the antihyperalgesic effect of duloxetine and amitriptyline. The plastic change of the descending noradrenergic system does not obviously affect the analgesic efficacy of duloxetine and amitriptyline.
Recent studies show that neuronal and glial plasticity are important for the therapeutic action of antidepressants. Here, we demonstrated that amitriptyline, a tricyclic antidepressant, significantly increased GDNF mRNA and GDNF release in C6 cells. Furthermore, different classes of antidepressants increased GDNF release, but non-antidepressant psychotropic drugs did not. The amitriptyline-induced GDNF release was completely inhibited by U0126, a mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor, but was not inhibited by H-89, a protein kinase A inhibitor or calphostin C, a protein kinase C inhibitor. These results suggest that the amitriptyline-induced GDNF release may be regulated through a MEK/MAPK pathway. Next, we examined the effects of monoamines on GDNF release, because antidepressants are known to increase monoamines. 5-HT increased GDNF mRNA and GDNF release, but noradrenaline and dopamine did not. The 5-HT-induced GDNF release was partially, but significantly, blocked by ketanserin, a 5-HT2A receptor antagonist. The 5-HT-induced GDNF release was completely inhibited by U0126, but was not inhibited by H-89 or calphostin C. These results suggest that the 5-HT-induced GDNF release was mediated through a MEK/MAPK pathway and, at least, 5-HT2A receptors. GDNF, as well as other neurotrophic factors, may contribute to explain the therapeutic action of antidepressants and suggest a novel strategy of pharmacological intervention.
For more Mechanism of Action (Complete) data for AMITRIPTYLINE (13 total), please visit the HSDB record page.
KEGG Target based Classification of Drugs
Solute carrier family
SLC6
SLC6A2 (NAT1) [HSA:6530] [KO:K05035]
Vapor Pressure
Pictograms
Corrosive;Acute Toxic;Irritant;Health Hazard;Environmental Hazard
Other CAS
Absorption Distribution and Excretion
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.
Amitriptyline
CAS No.: 50-48-6
Cat. No.: VC0518675
Molecular Formula: C20H23N
Molecular Weight: 277.4 g/mol
Purity: >98% (or refer to the Certificate of Analysis)
* For research use only. Not for human or veterinary use.
Specification
| Description | Amitriptyline is an organic tricyclic compound that is 10,11-dihydro-5H-dibenzo[a,d][7]annulene substituted by a 3-(dimethylamino)propylidene group at position 5. It has a role as an adrenergic uptake inhibitor, an antidepressant, an environmental contaminant, a xenobiotic and a tropomyosin-related kinase B receptor agonist. It is a tertiary amine and a carbotricyclic compound. It derives from a hydride of a dibenzo[a,d][7]annulene. Amitriptyline is a tricyclic antidepressant that has been used to treat depression for decades. ELAVIL, a previously approved branded product of amitriptyline, was first approved by the FDA in 1961. Amitriptyline has been investigated in the treatment of pain-related conditions, attributed to its analgesic properties. Amitriptyline is a Tricyclic Antidepressant. Amitriptyline is a tricyclic antidepressant that is widely used in the therapy of depression. Amitriptyline can cause mild and transient serum enzyme elevations and is rare cause of clinically apparent acute cholestatic liver injury. Amitriptyline is a derivative of dibenzocycloheptadiene and a tricyclic antidepressant. Amitriptyline inhibits the re-uptake of norepinephrine and serotonin by the presynaptic neuronal membrane in the central nervous system (CNS), thereby increasing the synaptic concentration of norepinephrine and serotonin. Due to constant stimulation to these receptors, amitriptyline may produce a downregulation of adrenergic and serotonin receptors, which may contribute to the antidepressant activity. AMITRIPTYLINE is a small molecule drug with a maximum clinical trial phase of IV (across all indications) that was first approved in 1961 and is indicated for depressive disorder and major depressive disorder and has 22 investigational indications. This drug has a black box warning from the FDA. Amitriptyline hydrochloride is a dibenzocycloheptene-derivative tricyclic antidepressant (TCA). TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, amitriptyline does not affect mood or arousal, but may cause sedation. In depressed individuals, amitriptyline exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Tertiary amine TCAs, such as amitriptyline, are more potent inhibitors of serotonin reuptake than secondary amine TCAs, such as nortriptyline. TCAs also down-regulate cerebral cortical β-adrenergic receptors and sensitize post-synaptic serotonergic receptors with chronic use. The antidepressant effects of TCAs are thought to be due to an overall increase in serotonergic neurotransmission. TCAs also block histamine-H1 receptors, α1-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively. See toxicity section below for a complete listing of side effects. Amitriptyline may be used to treat depression, chronic pain (unlabeled use), irritable bowel syndrome (unlabeled use), diabetic neuropathy (unlabeled use), post-traumatic stress disorder (unlabeled use), and for migraine prophylaxis (unlabeled use). Tricyclic antidepressant with anticholinergic and sedative properties. It appears to prevent the re-uptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antagonize cholinergic and alpha-1 adrenergic responses to bioactive amines. See also: Nortriptyline (related); Protriptyline (related); Amitriptyline Hydrochloride (active moiety of). |
|---|---|
| CAS No. | 50-48-6 |
| Molecular Formula | C20H23N |
| Molecular Weight | 277.4 g/mol |
| IUPAC Name | N,N-dimethyl-3-(2-tricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,11,13-hexaenylidene)propan-1-amine |
| Standard InChI | InChI=1S/C20H23N/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 |
| Standard InChI Key | KRMDCWKBEZIMAB-UHFFFAOYSA-N |
| Canonical SMILES | CN(C)CCC=C1C2=CC=CC=C2CCC3=CC=CC=C31 |
| Appearance | Solid powder |
| Boiling Point | 410.26°C (rough estimate) |
| Colorform | Crystals |
| Melting Point | 196-197 196 – 197 °C |
Amitriptyline | 50-48-6 – ChemicalBook
Amitriptyline (CAS 50-48-6) information, including chemical …
-
Boiling point: 410.26°C (rough estimate)
-
Melting point: 196-197°C
-
Density: 0.9415 (rough estimate)
-
refractive index: 1.7500 (estimate)
- CAS No.
- 50-48-6
- Chemical Name:
- Amitriptyline
- Synonyms
- Amitriptylin;amitriptilina;Amitryptiline;Amitryptyline;Elavil;5-(3-dimethylaminopropylidene)-10,11-dihyro-5h-dibenzo(a,d)cycloheptene;5-(3-Dimethylaminopropylidene)-10,11-dihydro-5H-dibenzo(a,d)cycloheptatriene;n750;elani;mk230
- CBNumber:
- CB1159271
- Molecular Formula:
- C20H23N
- Molecular Weight:
- 277.4
- MDL Number:
- MFCD00412072
- MOL File:
- 50-48-6.mol
- MSDS File:
- SDS
- TDS File:
- TDS
| Product description | Number | Pack Size | Price |
| Amitriptyline Purifiedfromascites. | A1382 | 500ug | $1699 |
| Amitriptyline 99.93% | CS-0009498 | 10mg | $54 |
| Amitriptyline 99.93% | CS-0009498 | 25mg | $97 |
| Amitriptyline 99.93% | CS-0009498 | 50mg | $135 |
| Amitriptyline 99.93% | CS-0009498 | 100mg | $184 |
| More product size | |||
| Melting point | 196-197°C |
|---|---|
| Boiling point | 410.26°C (rough estimate) |
| Density | 0.9415 (rough estimate) |
| refractive index | 1.7500 (estimate) |
| storage temp. | Store at -20°C |
| form | Liquid |
| pka | 9.4(at 25℃) |
| color | Colorless to light yellow |
| Water Solubility | 9.7 mg/mL |
| Stability | Light Sensitive |
| CAS DataBase Reference | 50-48-6(CAS DataBase Reference) |
| FDA UNII | 1806D8D52K |
| ATC code | N06AA09 |
| NIST Chemistry Reference | Amitriptyline(50-48-6) |
| EPA Substance Registry System | Amitriptyline (50-48-6) |
SAFETY
Risk and Safety Statements
| Symbol(GHS) |    GHS08,GHS09,GHS05 |
|---|---|
| Signal word | Danger |
| Hazard statements | H361-H301+H311+H331-H410-H318 |
| Precautionary statements | P273-P391-P501-P201-P202-P281-P308+P313-P405-P501-P280-P305+P351+P338-P310 |
| HazardClass | IRRITANT |
| Hazardous Substances Data | 50-48-6(Hazardous Substances Data) |
| REACH Registrations | Active |
Amitriptyline price
| Manufacturer | Product number | Product description | CAS number | Packaging | Price | Updated | Buy |
|---|---|---|---|---|---|---|---|
| Usbiological | A1382 | Amitriptyline Purifiedfromascites. | 500ug | $1699 | 2026-06-03 | Buy | |
| ChemScene | CS-0009498 | Amitriptyline 99.93% | 50-48-6 | 10mg | $54 | 2026-06-04 | Buy |
| ChemScene | CS-0009498 | Amitriptyline 99.93% | 50-48-6 | 25mg | $97 | 2026-06-04 | Buy |
| ChemScene | CS-0009498 | Amitriptyline 99.93% | 50-48-6 | 50mg | $135 | 2026-06-04 | Buy |
| ChemScene | CS-0009498 | Amitriptyline 99.93% | 50-48-6 | 100mg | $184 | 2026-06-04 | Buy |
Amitriptyline Chemical Properties, Uses, Production
Originator
Elavil HCl Merck Sharp and,Dohme,US,1961
Uses
Amitriptyline is used for anxious-depressive conditions. It is easier to tolerate than imipramine.
Uses
Antidepressant.
Definition
ChEBI: An organic tricyclic compound that is 10,11-dihydro-5H-dibenzo[a,d][7]annulene substituted by a 3-(dimethylamino)propylidene group at position 5.
Manufacturing Process
Phthalic anhydride is reacted with phenylacetic acid to form 3- benzylidenephthalide which is then hydrogenated to 2-phenethylbenzoic acid. Conversion to the acid chloride followed by intramolecular dehydrochlorination yields the ketone, 5H-dibenzo[a,d]cyclohepten-5-one. The ketone undergoes a Grignard reaction with 3-(dimethylamino)propyl chloride to give 5-(γ- dimethylaminopropylidene)-5H-dibenzo[a,d]cycloheptene.
Then, as described in US Patent 3,205,264, a solution of 5-(γ- dimethylaminopropylidene)-5H-dibenzo[a,d]cycloheptene (42 grams; 0.153 mol) in 105 ml of ethanol is hydrogenated over Raney nickel (1.5 grams) at 65°C under an initial hydrogen pressure of 450 lb. After 1 mol of hydrogen is absorbed (3.5 hours), the reaction mixture is filtered to remove the catalyst and is acidified with 80 ml of 2.5 N hydrochloric acid (0.2 mol). The acidic solution is concentrated to dryness under vacuum and is flushed three times with 100 ml of benzene to remove residual water. The solid residue then is dried under vacuum at 40°C to yield 44.9 grams (94% of theory) of the product, MP 187-189.5°C, equivalent weight 307, ultraviolet absorption A% 2380432. Recrystallization from isopropyl alcohol and ether affords the product in high purity.
In practice it is usually used as hydrochloride.
brand name
Elavil (AstraZeneca); Endep (Roche);Ami-anelun;Amilent;Amilit-ifi;Aminiurin;Amitimid;Amitriptol;Amyline;Amyzol;Annolytin;Apo-amitriptylline;Apo-pram;Deprelio;Deprestal;Diapatal;Elatrolet;Elavil plus;Emitrip;Enovil;Entrafon-210;Entrafon-2-10;Entrafon-2-25;Entrafon-a;Entrafon-forte;Etarfon;Etrafon-a;Etrafon-forte;Laroxal;Larozyl;Levate;Limbatarail;Limbatral;Limbitryl;Limitrol;Longopax;Loxaryl;Mareline;Meravil;Muaban d;Mutaban a/d/f;Nobrital;Novotriptyn;Novotryptin;Novo-tryptin;Parks-plus;Pms levazine;Prouvil;Saratem;Sarotena;Sedans;Sylvemid;Tensorelax;Teperin;Trepiline;Trepulin;Triptizol;Triptonal;Triptpane;Trivial-4-10.
Therapeutic Function
Antidepressant
World Health Organization (WHO)
Amitriptyline, a tricyclic antidepressant was introduced in 1961 for the management of endogenous depression and is listed in the 8th WHO Model List of Essential Drugs. Much of the adverse effects are caused by its antimuscarinic actions. These include dry mouth, cardiac arrhythmias, central nervous system disturbances, blood disorders and risk of suicide. The risk of suicide and dangers related to overdosage led the Norwegian Medicines Control Authority to put the higher strength formulation under prescribing restriction in 1992. The risk of death following overdosage is apparently higher for products containing tricyclic compounds as compared with nontricyclic products.
Biological Functions
Amitriptyline is a tertiary amine dibenzocycloheptadiene TCA with a propylidene side chain extending from the central carbocyclic ring. The diarylpropylideneamine moiety for amitriptyline makes it sensitive to photo-oxidation; therefore, its hydrochloride solutions should be protected from light to avoid ketone formation and precipitation.
Pharmacokinetics
Amitriptyline is rapidly absorbed from the GI tract and from parenteral sites.Amitriptyline and its active metabolite, nortriptyline, are distributed into breast milk. Amitriptyline is primarily (65%) metabolized by N-demethylation by CYP2D6 to nortriptyline and hydroxylation to its E-10-hydroxy metabolite. Nortriptyline is pharmacologically active as a secondary amine TCA. Amitriptyline shows approximately equal affinity for 5-HT and NE transporters.
Synthesis
Amitriptyline, 5-(3-dimethylaminopropyliden)-10,11-dihydrodibenzocycloheptene (7.1.4), differs from imipramine in that the nitrogen atom in the central part of the tricyclic system is replaced by a carbon, which is bound to a side chain by a double bond. Amitriptyline (7.1.4) is synthesized by interaction of 10,11-dihydro-N,N-dimethyl- 5H-dibenzo[a,d]cyclohepten-5-one with 3-dimethylaminopropylmagnesium bromide and the subsequent dehydration of the resulting tertiary alcohol (7.1.3) using hydrochloric acid [6–11].
An alternative way of synthesis of amitriptyline is by interaction of 10,11-dihydro-N,Ndimethyl-5H-dibenzo[a,d]-cyclohepten-5-one with cyclopropylmagnesium bromide, giving 10,11-dihydro-N,N-dimethyl-5H-dibenzo[a,d]-cyclohepten-5-cyclopropyl-5-ol (7.1.5). Reacting this with hydrogen bromide in acetic acid results in an opening of the cyclopropyl ring, which forms 5-(3-bromopropyliden)-10,11-dihydro-5H-dibenzo[a,d]-cycloheptene (7.1.6). Alkylating this with dimethylamine gives amitriptyline (7.1.4) [12,13].
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Amitriptyline (Elavil) | tricyclic antidepressant (TCA) | CAS# 50-48-6 …
Amitriptyline (Elavil) (CAS#: 50-48-6) is a tricyclic antidepressant (TCA) used for the treatment of major depressive disorder, …
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CAS: 50-48-6; 549-18-8
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Molecular Weight: 277.4 g/mol
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Molecular Formula: C20H23N
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Product Name: Amitriptyline
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Amitriptyline is used for anxious-depressive conditions. It is easier to tolerate than imipramine. Antidepressant. ChEBI: An organic …
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