IMIPRAMINE Chemical Properties

Melting point:

174°C

Boiling point:

bp0.1 160°

Density 

0.9935 (rough estimate)

refractive index 

1.5640 (estimate)

pka

pKa 9.66(H2O,t = 25,I=0.025) (Uncertain)

form 

Liquid

color 

Colorless to light yellow

Water Solubility 

18.23mg/L(24 ºC)

Solvent

Ethanol under nitrogen

Concentration

1 mCi/ml

Specific Activity

60-90 Ci/mmol

BCS Class

1

EPA Substance Registry System

Imipramine (50-49-7)

Safety Information

Hazardous Substances Data

50-49-7(Hazardous Substances Data)

Toxicity

A tertiary amine tricyclic antidepressant that is thought to exert its therapeutic effect by inhibiting the reuptake of serotonin and norepinephrine centrally. A major metabolite is N-desmethylimipramine (desipramine), also used as an antidepressant drug. Desipramine differs from imipramine in being a better blocker of norepinephrine, rather than serotonin, uptake. Side effects, including sedation and drowsiness, dry mouth, urinary retention, constipation, and orthostatic hypotension, are probably due to the anticholinergic, anti-α-adrenergic, and antihistaminergic receptor-blocking properties. Imipramine should not be used in conjunction with a monoamine oxidase inhibitor or other treatment that increases catecholamine concentrations (e.g., drugs containing sympathomimetic amines). Imipramine should be avoided in patients with cardiovascular disease or seizure disorder, or in those who may abuse alcohol, as imipramine lowers seizure threshold, can produce cardiovascular toxicity and may potentiate the effects of alcohol. Imipramine intoxication can include CNS abnormalities (e.g., drowsiness, stupor, coma, and extrapyramidal symptoms), cardiac arrhythmia, and respiratory depression. Children appear to be particularly vulnerable to the cardiotoxic and seizure-inducing effects of high doses of imipramine. The oral LD50 in female rats is 305 mg/kg.

IMIPRAMINE Usage And Synthesis

Originator

Tofranil,Ciba Geigy,France,1959

Uses

Imipramine is used in depression of various etiology accompanied by motor clumsiness and enuresis in children and Parkinson’s disease.

Uses

antidepressant

Definition

ChEBI: Imipramine is a dibenzoazepine that is 5H-dibenzo[b,f]azepine substituted by a 3-(dimethylamino)propyl group at the nitrogen atom. It has a role as an adrenergic uptake inhibitor, an EC 3.4.21.26 (prolyl oligopeptidase) inhibitor and an antidepressant. It derives from a hydride of a 5H-dibenzo[b,f]azepine.

Manufacturing Process

20 parts of imino dibenzyl are dissolved in 100 parts by volume of absolutely dry benzene. A suspension of 4 parts NaNH2 in 50 parts by volume of absolute benzene are then added dropwise at 50° to 60°C after which the mixture is boiled for an hour under reflux. 13 parts of 3-dimethylamino n_x0002_propyl chloride are then added dropwise at 40° to 50°C and the mixture is boiled for 10 hours under reflux. After cooling, the benzene solution is thoroughly washed with water, whereupon the basic constituents are extracted with dilute hydrochloric acid.
The hydrochloric extract is then made alkaline and the separated base is extracted with ether. After drying, the solvent is evaporated and the residue is distilled in the high vacuum, whereby the N-(3-dimethylaminopropyl)-imino dibenzyl passes over at a temperature of 160°C under 0.1 mm pressure. The chlorohydrate with a melting point of 174° to 175°C is obtained therefrom with alcoholic hydrochloric acid.

brand name

Janimine (Abbott); Pramine (Alra); Presamine (Sanofi Aventis); Tofranil (Novartis); Tofranil (Tyco).

Therapeutic Function

Antidepressant

Mechanism of action

Besides being used in the clinical treatment of depression, imipramine also has been used for the treatment of functional enuresis in children who are at least 6 years of age (25 mg daily administered 1 hour before bedtime, not to exceed 2.5 mg/kg daily).

Clinical Use

Imipramine is a 10,11-dihydrodibenzazepine tertiary amine TCA that is marketed as hydrochloride and pamoate salts, both of which are administered orally. Although the hydrochloride salt may be administered in divided daily doses, imipramine's long duration of action suggests that the entire oral daily dose may be administered at one time.On the other hand, imipramine pamoate usually is administered as a single daily oral dose.

Synthesis

Imipramine, 5-[3-(dimethylamino)propyl]-10,11-dihydro-5H-dibenz[b,f] azepine (7.1.1), is synthesized by the alkylation of 10,11-dihydro-5H-dibenz[b,f]azepine using 3-dimethylaminopropylchloride in the presence of sodium amide [1¨C3].

IMIPRAMINE(50-49-7)Related Product Information

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