DESIPRAMINE Property

Melting point:

212°C

Boiling point:

bp0.02 172-174°

Density 

0.9934 (rough estimate)

refractive index 

1.5200 (estimate)

pka

pKa 10.21(-)(H2O t=20) (Uncertain)

form 

powder

color 

white

EPA Substance Registry System

Desipramine (50-47-5)

Safety

Hazard Codes 

Xn

Risk Statements 

20/21/22

Safety Statements 

36

WGK Germany 

3

Hazardous Substances Data

50-47-5(Hazardous Substances Data)

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H302Harmful if swallowed

H336May cause drowsiness or dizziness

H370Causes damage to organs

Precautionary statements

P260Do not breathe dust/fume/gas/mist/vapours/spray.

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P271Use only outdoors or in a well-ventilated area.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

P307+P311IF exposed: call a POISON CENTER or doctor/physician.

P312Call a POISON CENTER or doctor/physician if you feel unwell.

P321Specific treatment (see … on this label).

P330Rinse mouth.

P403+P233Store in a well-ventilated place. Keep container tightly closed.

P405Store locked up.

P501Dispose of contents/container to..…

DESIPRAMINE Chemical Properties,Usage,Production

Originator

Pertofran,Geigy,UK,1963

Uses

Desipramine is used for depression of various etiology and in particular for endogenous depression.

Uses

Antidepressant.

Definition

ChEBI: A dibenzoazepine consisting of 10,11-dihydro-5H-dibenzo[b,f]azepine substituted on nitrogen with a 3-(methylamino)propyl group.

Manufacturing Process

Oxidative coupling of o-nitrotoluene gives 4,4'-dinitrodibenzyl which is reduced with hydrogen to the diamine. The diamine is pyrolyzed to give dihydrobenzazepine. This is reacted with N-(3-chloropropyl)-Nmethylbenzamine to give N-benzyldesipramine. This is debenzylated by reductive cleavage and then reacted with HCl.

brand name

Norpramin (Sanofi Aventis); Pertofrane (Sanofi Aventis).

Therapeutic Function

Psychostimulant

Mechanism of action

Its antidepressant effect results from increases in the level of NE in CNS synapses, and long-term administration causes a downregulation of α1-adrenoceptors and desensitization of presynaptic α2-receptors, equilibrating the noradrenergic system and, thus, correcting the dysregulated output of depressed patients. The SSRIs do not produce this effect. Desipramine also downregulates the NET, but not the 5-SERT . Substantial loss of NE transporter–binding sites takes 15 days to occur and is accompanied by a marked reduction of NET function in vivo. Desipramine has weak effects on 5-HT reuptake.

Synthesis

Desipramine, 10,11-dihydro-5-[3-(methylamino)propyl]-5H-dibenz[b,f] azepine (7.1.13), differs from imipramine in that it contains only one methyl group on the nitrogen atom of the propylamine side chain. The suggested methods of desipramine synthesis are very simple, and the difference lies only in the manner in which the secondary methylamine group is introduced into the structure of the drug.
The first way of synthesis is by the alkylation of 10,11-dihydro-5H-dibenz[b,f]azepine using 1-bromo-3-chloropropane in the presence of sodium amide into a chloro derivative (7.1.12) and the subsequent reaction of this with methylamine, giving desipramine (7.1.13) [18–20].

Finally, a second way of synthesis is from imipramine (7.1.1), which undergoes demethylation by successive reaction with ethyl chloroformate, giving 5-[3-(N-carbethoxy-N-methyl)aminopropyl]-10,11-dihydro-5H-dibenz[b,f]azepine (7.1.15), the alkaline hydrolysis of which leads to desipramine (7.1.13) [23,24].

Metabolism

Desipramine is a dihydrodibenzazepine secondary amine TCA that also is the active metabolite of imipramine. Desipramine appears to have a bioavailability comparable to the other secondary TCAs. Desipramine is distributed into milk in concentrations similar to those present at steady state in maternal plasma. This drug is metabolized primarily by CYP2D6 to its 2-hydroxy metabolite and by CYP1A2 and CYP2C19 to its N-demethylated (primary amine) metabolite . Desipramine exhibits a greater potency and selectivity for the NET than the other secondary TCAs do.