Metapramine Property

Melting point:

237-240 °C

Boiling point:

350.8±42.0 °C(Predicted)

Density 

1.12±0.1 g/cm3(Predicted)

storage temp. 

Hygroscopic, -20°C Freezer, Under inert atmosphere

solubility 

DMSO (Slightly), Methanol (Slightly)

form 

Oil

pka

9.09±0.20(Predicted)

color 

Colourless to Pale Yellow

Stability:

Hygroscopic

Hazard and Precautionary Statements (GHS)

Metapramine Chemical Properties,Usage,Production

Description

Metapramine is an antidepressant with a pharmacological profile similar to the tricyclics and an apparent rapid clinical onset of action. Metapramine differs biochemically from the tricyclics in that it markedly enhances norepinephrine turnover with minimal inhibition of reuptake. Like the tricyclics, however, it does down regulate β-receptors.

Originator

Rhone-Poulenc (France)

Uses

Metapramine is a tricyclic antidepressant derived from dibenzoazepine. Metapramine acts as a norepinephrine reuptake inhibitor without affecting the reuptake of serotonin or dopamine.

Definition

ChEBI: Metapramine is a dibenzooxazepine.

Manufacturing Process

5-Methyl-dibenzo[b,f]azepine (4.1 g), N-diethylaminoborane (1.7 g) and freshly distilled toluene (150 cc) are introduced into a 500 cc three-neck flask equipped with a dropping funnel and a condenser, and protected against moisture by a calcium chloride guard tube. The solution is heated under reflux (110°C) for 22 hours under a nitrogen atmosphere and then cooled. A 2 N aqueous sodium hydroxide solution (33 cc) is then run in followed by an 0.316 N aqueous methylchloramine solution (190 cc), the addition of which takes 9 minutes. The mixture is stirred for 1 hour and then decanted. The organic layer is washed with water until it has a pH of 6 and is then extracted with 2 N hydrochloric acid (5 times 50 cc), dried over sodium sulfate, filtered and evaporated. Recrystallization of the residue from petroleum ether yields some unconverted 5-methyl-dibenzo[b,f]azepine (2.17 g).
The aqueous acid solution is rendered alkaline by adding 2 N sodium hydroxide solution. After extracting with diethyl ether (3 times 100 cc), drying the extracts over potassium carbonate, treating them with decolorizing charcoal, filtering and evaporating the ether, a yellowish oil (0.9 g), identified as 5-methyl-10-methylamino-10,11-dihydrodibenzo[b,f]azepine, is obtained in a yield of 37.5%.
Methylchloramine can be prepared by adding an aqueous solution of sodium hypochlorite to an aqueous solution of methylamine in accordance with the process described by W.S. Metcalf, J. Chem. Soc.1942,148.

brand name

TIMAXEL

Therapeutic Function

Antidepressant