amitriptyline N-oxide Property

Melting point:

228-230°; mp 102-103°

Boiling point:

435.25°C (rough estimate)

Density 

1.0552 (rough estimate)

refractive index 

1.6000 (estimate)

storage temp. 

Amber Vial, -86°C Freezer, Under inert atmosphere

solubility 

Chloroform (Slightly), Methanol (Slightly)

form 

Solid

color 

White to Off-White

Stability:

Light and Temperature Sensitive

Safety

Toxicity

LD50 in mice, guinea pigs, rabbits, dogs (mg/kg): between 330-460 orally; in mice, rats: 87, 25 i.v.; 320, 110 i.p. (Friehe, Fontaine).

Hazard and Precautionary Statements (GHS)

amitriptyline N-oxide Chemical Properties,Usage,Production

Originator

Equilibrin,Nattermann,W. Germany,1980

Uses

Amitriptyline N-oxide is used in biological studies to metabolize drugs by fungi colonizing cadavers using LC-ESI-MS/MS and GC-MS. This compound is also used in the development of antidepressant drugs.

Definition

ChEBI: Amitriptylinoxide is an organic tricyclic compound.

Manufacturing Process

31.3 g (0.1 mol) of 3-(3'-dimethylaminopropylidene)dibenzo[a,d]cyclohepta- 1,4-diene hydrochloride are dissolved in water, and the free base is liberated by means of a 28% aqueous solution of sodium hydroxide. The free base is sucked off, washed with water, and dissolved in 100 ml of methanol. To the solution are added 31 ml of 30% hydrogen peroxide. After 7 days, the reaction mixture is diluted with 200 ml of water, and the major part of the methanol is evaporated in vacuum. The precipitated N-oxide crystals are filtered off, washed with water, and dried, yielding 27 g of the dihydrate of 3- (3'-dimethylaminopropylidene)dibenzo[a,d]cyclohepta-1,4-diene N-oxide with melting point of 102° to 103°C. In dehydrated state the melting point is 228°C to 230°C.
By dissolving the N-oxide in acetone, and bubbling dry hydrogen chlorine gas through the solution until slightly acid reaction, the hydrochloride of the Noxide is precipitated as a white crystalline substance with melting point of 172°C to 173.6°C.
The starting material can be prepared in known manner from dibenzo[a,d]cyclohepta-1,4-diene-5-one by a Grignard reaction with 3- dimethylaminopropyl magnesium chloride, hydrolysis and dehydration of the resulting carbinol.

Therapeutic Function

Antidepressant

Safety Profile

Poison by ingestion,intraperitoneal, and intravenous routes. An experimentalteratogen. Other experimental reproductive effects. Whenheated to decomposition it emits toxic fumes of NOx.