CAS 549-18-8|Amitriptyline Hydrochloride

Introduction：Basic information about CAS 549-18-8|Amitriptyline Hydrochloride, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Amitriptyline Hydrochloride BiologicalActivity
3. Chemical & Physical Properties
4. Toxicological Information
CHEMICAL IDENTIFICATION
HEALTH HAZARD DATA
ACUTE TOXICITY DATA
MUTATION DATA
5. Safety Information
6. Articles61
7. Synonyms

Common Name	Amitriptyline Hydrochloride
CAS Number	549-18-8	Molecular Weight	313.864
Density	1.076g/cm3	Boiling Point	398.2ºC at 760 mmHg
Molecular Formula	C₂₀H₂₄ClN	Melting Point	196-197°C
MSDS	ChineseUSA	Flash Point	11 °C
Symbol	GHS02, GHS06, GHS08	Signal Word	Danger

Names

Name	Amitriptyline hydrochloride
Synonym	More Synonyms

Amitriptyline Hydrochloride BiologicalActivity

Description	Amitriptyline Hydrochloride is a dibenzocycloheptene-derivative tricyclic antidepressant (TCA).Target: OthersAmitriptyline acts primarily as a serotonin-norepinephrine reuptake inhibitor, with strong actions on the serotonin transporter and moderate effects on the norepinephrine transporter. It has negligible influence on the dopamine transporter and therefore does not affect dopamine reuptake, being nearly 1,000 times weaker on it than on serotonin [1]. Amitriptyline additionally functions as a 5-HT2A, 5-HT2C, 5-HT3, 5-HT6, 5-HT7, α1-adrenergic, H1, H2, and mACh receptorantagonist, and σ1 receptor agonist. It has also been shown to be a relatively weak NMDA receptor negative allosteric modulator at the same binding site as phencyclidine. Amitriptyline inhibits sodium channels, L-type calcium channels, and Kv1.1, Kv7.2, and Kv7.3 voltage-gated potassium channels, and therefore acts as a sodium, calcium, and potassium channel blocker as well [2]. Recently, amitriptyline has been demonstrated to act as an agonist of the TrkA and TrkB receptors. It promotes the heterodimerization of these proteins in the absence of NGF and has potent neurotrophic activity both in-vivo and in-vitro in mouse models [3].
Related Catalog	Signaling Pathways >>Membrane Transporter/Ion Channel >>Sodium ChannelResearch Areas >>Neurological Disease
References	[1]. Tatsumi, M., et al., Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol, 1997. 340(2-3): p. 249-58. [2]. http://en.wikipedia.org/wiki/Amitriptyline [3]. Jang, S.W., et al., Amitriptyline is a TrkA and TrkB receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity. Chem Biol, 2009. 16(6): p. 644-56.

Description

Amitriptyline Hydrochloride is a dibenzocycloheptene-derivative tricyclic antidepressant (TCA).Target: OthersAmitriptyline acts primarily as a serotonin-norepinephrine reuptake inhibitor, with strong actions on the serotonin transporter and moderate effects on the norepinephrine transporter. It has negligible influence on the dopamine transporter and therefore does not affect dopamine reuptake, being nearly 1,000 times weaker on it than on serotonin [1]. Amitriptyline additionally functions as a 5-HT2A, 5-HT2C, 5-HT3, 5-HT6, 5-HT7, α1-adrenergic, H1, H2, and mACh receptorantagonist, and σ1 receptor agonist. It has also been shown to be a relatively weak NMDA receptor negative allosteric modulator at the same binding site as phencyclidine. Amitriptyline inhibits sodium channels, L-type calcium channels, and Kv1.1, Kv7.2, and Kv7.3 voltage-gated potassium channels, and therefore acts as a sodium, calcium, and potassium channel blocker as well [2]. Recently, amitriptyline has been demonstrated to act as an agonist of the TrkA and TrkB receptors. It promotes the heterodimerization of these proteins in the absence of NGF and has potent neurotrophic activity both in-vivo and in-vitro in mouse models [3].

Related Catalog

Signaling Pathways >>Membrane Transporter/Ion Channel >>Sodium ChannelResearch Areas >>Neurological Disease

References

[1]. Tatsumi, M., et al., Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol, 1997. 340(2-3): p. 249-58.

[2]. http://en.wikipedia.org/wiki/Amitriptyline

[3]. Jang, S.W., et al., Amitriptyline is a TrkA and TrkB receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity. Chem Biol, 2009. 16(6): p. 644-56.

Chemical & Physical Properties

Density	1.076g/cm3
Boiling Point	398.2ºC at 760 mmHg
Melting Point	196-197°C
Molecular Formula	C₂₀H₂₄ClN
Molecular Weight	313.864
Flash Point	11 °C
Exact Mass	313.159729
PSA	3.24000
LogP	4.97060
InChIKey	KFYRPLNVJVHZGT-UHFFFAOYSA-N
SMILES	CN(C)CCC=C1c2ccccc2CCc2ccccc21.Cl
Storage condition	2-8°C
Water Solubility	H2O: soluble

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: HO9450000

CHEMICAL NAME :: 5H-Dibenzo(a,d)cycloheptene-delta(sup 5),gamma-propylamine, 10,11-dihydro-N,N-dimethyl-, hydrochloride

CAS REGISTRY NUMBER :: 549-18-8

LAST UPDATED :: 199707

DATA ITEMS CITED :: 39

MOLECULAR FORMULA :: C20-H23-N.Cl-H

MOLECULAR WEIGHT :: 313.90

WISWESSER LINE NOTATION :: L C676 BY&T&J BU3N1&1 &GH

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - child

DOSE/DURATION :: 58 mg/kg

TOXIC EFFECTS :: Behavioral - coma Vascular - BP lowering not characterized in autonomic section Lungs, Thorax, or Respiration - respiratory depression

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 714 ug/kg/1D-I

TOXIC EFFECTS :: Behavioral - alteration of operant conditioning Behavioral - changes in psychophysiological tests

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 60 mg/kg/3W-I

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - ataxia Behavioral - withdrawal

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 10 mg/kg

TOXIC EFFECTS :: Behavioral - hallucinations, distorted perceptions

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - child

DOSE/DURATION :: 62500 ug/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Vascular - BP lowering not characterized in autonomic section Lungs, Thorax, or Respiration - respiratory depression

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - child

DOSE/DURATION :: 4167 ug/kg

TOXIC EFFECTS :: Behavioral - sleep Behavioral - hallucinations, distorted perceptions Behavioral - muscle contraction or spasticity

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human

DOSE/DURATION :: 200 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - muscle contraction or spasticity Behavioral - coma

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - child

DOSE/DURATION :: 62500 ug/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 19 mg/kg

TOXIC EFFECTS :: Behavioral - coma Lungs, Thorax, or Respiration - dyspnea

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 14286 ug/kg

TOXIC EFFECTS :: Behavioral - coma Lungs, Thorax, or Respiration - dyspnea

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 240 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Lungs, Thorax, or Respiration - dyspnea

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 67 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 385 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 14 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 140 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 65 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 80 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Lungs, Thorax, or Respiration - cyanosis

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 21 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 200 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >27 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intramuscular

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >23 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 20300 ug/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Vascular - BP lowering not characterized in autonomic section

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - cat

DOSE/DURATION :: 37 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 9900 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - guinea pig

DOSE/DURATION :: 52 mg/kg

TOXIC EFFECTS :: Cardiac - other changes

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 3200 mg/kg/32D-C

TOXIC EFFECTS :: Liver - other changes Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 24640 mg/kg/1Y-I

TOXIC EFFECTS :: Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 220 mg/kg

SEX/DURATION :: female 1-22 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - stillbirth Reproductive - Effects on Newborn - behavioral

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 70 mg/kg

SEX/DURATION :: male 5 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 60 mg/kg

SEX/DURATION :: female 9 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - Central Nervous System

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 60 mg/kg

SEX/DURATION :: female 9 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 60 mg/kg

SEX/DURATION :: female 8 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - body wall Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 70300 ug/kg

SEX/DURATION :: female 8 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Parenteral

DOSE :: 60 mg/kg

SEX/DURATION :: female 8 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - body wall

TYPE OF TEST :: Sex chromosome loss and nondisjunction

MUTATION DATA

TEST SYSTEM :: Rodent - mouse

DOSE/DURATION :: 70 mg/kg/5D

REFERENCE :: IMSCE2 IRCS Medical Science. (Lancaster, UK) V.12-14, 1984-86. For publisher information, see MSCREJ. Volume(issue)/page/year: 14,579,1986 *** REVIEWS *** TOXICOLOGY REVIEW IDPYAK Industrial Pharmacology. (Mount Kisco, NY) V.1-3, 1974-79. Discontinued. Volume(issue)/page/year: 2,209,1975 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X5594 No. of Facilities: 69 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 514 (estimated) No. of Female Employees: 266 (estimated)

Safety Information

Symbol	GHS02, GHS06, GHS08
Signal Word	Danger
Hazard Statements	H225-H301 + H311 + H331-H370
Precautionary Statements	P210-P260-P280-P301 + P310-P311
Personal Protective Equipment	Eyeshields;Faceshields;full-face particle respirator type N100 (US);Gloves;respirator cartridge type N100 (US);type P1 (EN143) respirator filter;type P3 (EN 143) respirator cartridges
Hazard Codes	T:Toxic
Risk Phrases	R23/24/25;R36/37/38;R42/43;R63
Safety Phrases	S22-S26-S36/37/39-S45-S36/37-S16
RIDADR	UN 2811 6.1/PG 3
WGK Germany	3
RTECS	HO9450000
Packaging Group	III
Hazard Class	6.1(b)

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Synonyms

Amitriptyline Hydrochloride

3-(5,6-dihydrodibenzo[2,1-b:2',1'-f][7]annulen-11-ylidene)-N,N-dimethylpropan-1-amine,hydrochloride

3-(10,11-Dihydro-5H-dibenzo[a,d][7]annulen-5-yliden)-N,N-dimethylpropan-1-aminhydrochlorid

3-(10,11-Dihydro-5H-dibenzo[a,d][7]annulen-5-ylidene)-N,N-dimethylpropan-1-amine hydrochloride (1:1)

EINECS 208-964-6

1-Propanamine, 3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-N,N-dimethyl-, hydrochloride (1:1)

1-propanamine, 3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-N,N-dimethyl-, hydrochloride

MFCD00012537

Amitriptyline HCl

3-(10,11-dihydro-5H-dibenzo[a,d][7]annulén-5-ylidène)-N,N-diméthylpropan-1-amine chlorhydrate

3-(10,11-Dihydro-5H-dibenzo[a,d][7]annulen-5-ylidene)-N,N-dimethyl-1-propanamine hydrochloride (1:1)

3-(10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-ylidene)-N,N-dimethylpropan-1-amine hydrochloride

5-(3-Dimethylaminopropylidene)dibenzo[a,d][1,4]cycloheptadiene hydrochloride

10,11-Dihydro-N,N-dimethyl-5H-dibenzo[a,d]cycloheptene-δ5,γ-propylamine hydrochloride

Amitriptyline (hydrochloride)

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