113-52-0

Usage

Uses

1. Used in Pharmaceutical Industry:
Imipramine hydrochloride is used as a tricyclic antidepressant for the treatment of major depression. It works by inhibiting the reuptake of serotonin and norepinephrine, thereby increasing their availability in the synaptic cleft and enhancing mood regulation.
2. Used in Psychiatry:
Imipramine hydrochloride is used as an antidepressant and a 5-HT transport inhibitor, particularly for patients suffering from major depression. Its action on the serotonin transporter makes it an effective treatment option for this condition.
3. Used in Urology:
Imipramine hydrochloride is used as a serotonin uptake inhibitor for the treatment of enuresis, a condition characterized by the inability to control urination. By modulating serotonin levels, it can help improve bladder control in affected individuals.
4. Used in Mental Health:
Imipramine hydrochloride has been evaluated for use in panic disorder, a condition marked by sudden and intense feelings of fear or anxiety. Its action on serotonin and norepinephrine transporters may help alleviate the symptoms of panic disorder.
Brand Names:
Some of the brand names under which Imipramine hydrochloride is marketed include Janimine (Abbott), Pramine (Alra), Presamine (Sanofi Aventis), Tofranil (Novartis), and Tofranil (Tyco).

Originator

Tofranil,Ciba Geigy,France,1959

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.

Therapeutic Function

Antidepressant

Biological Activity

imipramine (hydrochloride) is a tricyclic antidepressant and is mainly used in the treatment of major depression and enuresis [1].antidepressants are antagonists of many neurotransmitter receptors in human brain [3].imipramine is the first tricyclic antidepressant that acts mainly as an inhibitor of serotonin and norepinephrine transporters [2]. in radioligand binding assays, imipramine inhibited serotonin and norepinephrine transporters with kd values of 1.4 and 37 nm, respectively [2]. imipramine is also inhibited histamine h1 receptor, muscarinic acetylcholine receptor and α1-adrenergic receptor with kd values of 37, 46, and 32 nm, respectively [4].in rodents, imipramine abolished the depressive syndrome produced by the acute administration of reserpine. imipramine also possessed central anticholinergic activity and attenuate the activity of the centrally acting muscarinic agents tremorine and oxotremorine. imipramine inhibited the presynaptic uptake of na and 5-ht, and relatively weak against da [1].

Biochem/physiol Actions

Tricyclic antidepressant; inhibits the serotonin and norepinephrine transporters with Kis of 7.7 nM and 67 nM, respectively. Has little effect on the dopamine transporter (Ki = 25 μM).

Clinical Use

The demethylated metabolite is less anticholinergic, lesssedative, and more stimulatory and is a SNERI.Consequently, a patient treated with imipramine has twocompounds that contribute to activity. Overall, the effect isnonselective 5-HT versus NE reuptake.

Safety Profile

Human poison by ingestion. An experimental poison by ingestion, intravenous, subcutaneous, and intraperitoneal routes. An experimental teratogen. Human systemic effects by ingestion: sleep, somnolence, convulsions, muscle contraction or spasticity, coma, blood pressure decrease, dyspnea (difficulty in breathing), paresthesia (abnormal sensations), and kidney changes. Experimental reproductive effects. Mutation data reported. Used in the treatment of depression. When heated to decomposition it emits very toxic fumes of NO, and HCl. See also DIAZEPAM.

Veterinary Drugs and Treatments

In dogs and cats, imipramine has been used to treat cataplexy and urinary incontinence. In horses, imipramine has been used to treat narcolepsy and ejaculatory dysfunction (no parenteral dosage forms available).

Drug interactions

Potentially hazardous interactions with other drugs Alcohol: increased sedative effect. Analgesics: increased risk of CNS toxicity with tramadol; possibly increased risk of side effects with nefopam; possibly increased sedative effects with opioids. Anti-arrhythmics: increased risk of ventricular arrhythmias with amiodarone - avoid; increased risk of ventricular arrhythmias with disopyramide, flecainide or propafenone; avoid with dronedarone. Antibacterials: increased risk of ventricular arrhythmias with delamanid, moxifloxacin and possibly telithromycin - avoid with delamanid and moxifloxacin. Anticoagulants: may alter anticoagulant effect of coumarins. Antidepressants: enhanced CNS excitation and hypertension with MAOIs and moclobemide - avoid; concentration possibly increased with SSRIs; risk of ventricular arrhythmias with citalopram and escitalopram - avoid; possible increased risk of convulsions with vortioxetine. Antiepileptics: convulsive threshold lowered; concentration reduced by carbamazepine, phenobarbital and possibly fosphenytoin, phenytoin and primidone. Antimalarials: avoid with artemether/lumefantrine and piperaquine with artenimol. Antipsychotics: increased risk of ventricular arrhythmias especially with droperidol, fluphenazine, haloperidol, pimozide, sulpiride and zuclopenthixol - avoid; increased antimuscarinic effects with clozapine and phenothiazines; concentration increased by antipsychotics. Antivirals: increased risk of ventricular arrhythmias with saquinavir - avoid; concentration possibly increased with ritonavir. Atomoxetine: increased risk of ventricular arrhythmias and possibly convulsions. Beta-blockers: increased risk of ventricular arrhythmias with sotalol; concentration increased by labetalol and propranolol. Clonidine: tricyclics antagonise hypotensive effect; increased risk of hypertension on clonidine withdrawal. Dapoxetine: possibly increased risk of serotonergic effects - avoid. Dopaminergics: avoid use with entacapone; CNS toxicity reported with selegiline and rasagiline. Pentamidine: increased risk of ventricular arrhythmias. Sympathomimetics: increased risk of hypertension and arrhythmias with adrenaline and noradrenaline; metabolism possibly inhibited by methylphenidate.

Metabolism

Imipramine is extensively demethylated by first-pass metabolism in the liver, to its primary active metabolite, desipramine (desmethylimipramine). Paths of metabolism of both imipramine and desipramine include hydroxylation and N-oxidation. About 80% is excreted in the urine and about 20% in the faeces, mainly in the form of inactive metabolites. Urinary excretion of unchanged imipramine and of the active metabolite desipramine is about 5% and 6% respectively. Only small quantities of these are excreted in the faeces.

references

[1]. spencer ps. review of the pharmacology of existing antidepressants. br j clin pharmacol. 1977;4suppl 2:57s-68s.[2]. tatsumi m, groshan k, blakely rd, et al. pharmacological profile of antidepressants and related compounds at human monoamine transporters. eur j pharmacol. 1997 dec 11;340(2-3):249-58.[3]. cusack b, nelson a, richelson e. binding of antidepressants to human brain receptors: focus on newer generation compounds. psychopharmacology (berl). 1994 may;114(4):559-65.

InChI:InChI=1/C20H25N.ClH/c1-21(2)15-7-12-20-18-10-5-3-8-16(18)13-14-17-9-4-6-11-19(17)20;/h3-6,8-11,20H,7,12-15H2,1-2H3;1H

Synthetic route

Reaxys ID: 19040915 → Imipramine hydrochloride (113-52-0)

Conditions	Yield
Stage #1: In acetone for 0.5h; Heating / reflux; Stage #2: In di-isopropyl ether at 0 - 5℃;

Imipramine hydrochloride (113-52-0) + water (7732-18-5) + potassium hexacyanoferrate(III) → imipraminium ferricyanide monohydrate

Conditions	Yield
In water E-2 M solns. were mixed; ppt. was filtered, thoroughly washed with distd. water, dried at room temp., elem. anal.;	99.5%

sodium hexanitro cobaltate(III) + Imipramine hydrochloride (113-52-0) + water (7732-18-5) → imipraminium cobaltnitrite monohydrate

Conditions	Yield
In water E-2 M solns. were mixed; ppt. was filtered, thoroughly washed with distd. water, dried at room temp., elem. anal.;	99.5%

Imipramine hydrochloride (113-52-0) + sodium salicylate (54-21-7) → imipramine salicylate (1085510-17-3)

Conditions	Yield
In water at 20 - 62℃; for 19.95h;	95.1%
In water at 20 - 62℃; for 19.95h;	95.1%

Imipramine hydrochloride (113-52-0) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → 2-Formylimipramine (6487-79-2)

Conditions	Yield
With trichlorophosphate at 100℃; for 4h; Formylation; Vilsmeier Reaction;	59%

Imipramine hydrochloride (113-52-0) + orthoformic acid triethyl ester (122-51-0) → [3-(2-{Bis-[5-(3-dimethylamino-propyl)-10,11-dihydro-5H-dibenzo[b,f]azepin-2-yl]-methyl}-10,11-dihydro-dibenzo[b,f]azepin-5-yl)-propyl]-dimethyl-amine (129961-34-8)

Conditions	Yield
With tetrafluoroboric acid diethyl ether In diethyl ether; dichloromethane for 6h; Ambient temperature;	8%

Imipramine hydrochloride (113-52-0) → desipramine (50-47-5) + 9,10-dihydrodibenzazepine (494-19-9) + 10-Hydroxyimipramine (796-28-1)

Conditions	Yield
In water Ambient temperature; M. griseo-cyanus (ATCC 1207a); further microbial agents;	A 10 mg B n/a C n/a

Imipramine hydrochloride (113-52-0) → desipramine (50-47-5) + 9,10-dihydrodibenzazepine (494-19-9) + 10-Hydroxyimipramine (796-28-1) + 2-hydroxyimipramine (303-70-8)

Conditions	Yield
In water for 480h; Ambient temperature; C. blakesleeana (ATCC 8688a); further microbial agents; Further byproducts given;	A n/a B n/a C 30 mg D 88 mg

Imipramine hydrochloride (113-52-0) → 9,10-dihydrodibenzazepine (494-19-9) + 10-Hydroxyimipramine (796-28-1) + 2-hydroxyimipramine (303-70-8) + imipramine N-oxide (6829-98-7)

Conditions	Yield
In water; N,N-dimethyl-formamide for 480h; Ambient temperature; C. blakesleeana (ATCC 8688a); further microbial agents; Further byproducts given;	A n/a B 30 mg C 88 mg D n/a

Imipramine hydrochloride (113-52-0) → 9,10-dihydrodibenzazepine (494-19-9) + imipramine N-oxide (6829-98-7)

Conditions	Yield
In water; N,N-dimethyl-formamide for 360h; Ambient temperature; F. oxysporum f. sp. cepae (ATCC 11711); further microbial agents;	A 7 mg B n/a
In water for 312h; Ambient temperature; A. flavipes (ATCC 16795); further microbial agents;	A n/a B 112 mg

Imipramine hydrochloride (113-52-0) → C19H20(2)H4N2*ClH (61361-33-9)

Conditions	Yield
With deuteroacetic acid; sulfuric acid-d2 at 100℃; for 1.5h; in sealed tube; Yield given;

pyrocatechol violet + Imipramine hydrochloride (113-52-0) → 2-{(3,4-Dihydroxy-phenyl)-[3-hydroxy-4-oxo-cyclohexa-2,5-dien-(E)-ylidene]-methyl}-benzenesulfonic acid; compound with [3-(10,11-dihydro-dibenzo[b,f]azepin-5-yl)-propyl]-dimethyl-amine

Conditions	Yield
With sulfuric acid

Imipramine hydrochloride (113-52-0) → C38H48N4*2H(1+)

Conditions	Yield
With iron(III) chloride; acetic acid at 75℃; for 0.0833333h;

Imipramine hydrochloride (113-52-0) → 9,10-dihydrodibenzazepine (494-19-9) + Dimethyl-propylidene-ammonium

Conditions	Yield
at 280 - 326℃; Kinetics;

Imipramine hydrochloride (113-52-0) → desipramine (50-47-5) + 2-hydroxyimipramine (303-70-8)

Conditions	Yield
With NADP; cDNA-expressed human recombinant CYP1A2 In phosphate buffer at 37℃; for 0.25h; pH=7.4; Enzyme kinetics; Further Variations:; concentration;

Imipramine hydrochloride (113-52-0) → 2-hydroxyimipramine (303-70-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: 59 percent / POCl3 / 4 h / 100 °C 2: m-CPBA; TFA / CH2Cl2 / 2 h / 5 - 20 °C 3: conc. HCl / methanol / 2 h View Scheme

Imipramine hydrochloride (113-52-0) → formic acid 5-(3-dimethylamino-propyl)-10,11-dihydro-5H-dibenzo[b,f]azepin-2-yl ester (134150-88-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 59 percent / POCl3 / 4 h / 100 °C 2: m-CPBA; TFA / CH2Cl2 / 2 h / 5 - 20 °C View Scheme

Imipramine hydrochloride (113-52-0) + 3-Hydroxy-2-naphthoic acid (92-70-6) → imipramine xinafoate (1085510-09-3)

Conditions	Yield
In water at 25 - 50℃; for 20h;

disodium pamoate + Imipramine hydrochloride (113-52-0) → imipramine pamoate

Conditions	Yield
Stage #1: disodium pamoate; Imipramine hydrochloride In water; acetone at 20 - 55℃; Stage #2: In water at 40 - 70℃;
In water at 5℃;

impramine (50-49-7) + Imipramine hydrochloride (113-52-0) + embonic acid disodium salt (6640-22-8, 7681-47-2, 15537-67-4) → imipramine pamoate (10075-24-8)

Conditions	Yield
With sodium hydroxide In water

Imipramine hydrochloride (113-52-0) → 9,10-dihydrodibenzazepine (494-19-9)

Conditions	Yield
With peroxidase from horseradish type VI; dihydrogen peroxide at 37℃; for 1h; pH=7; aq. phosphate buffer; Enzymatic reaction;

Imipramine hydrochloride (113-52-0) → imipramine hydrochloride di-zinc chloride

Conditions	Yield
With zinc(II) chloride at 60 - 100℃; for 24h; Inert atmosphere; Sealed tube;

Imipramine hydrochloride (113-52-0) → 2-hydroxyimipramine (303-70-8) + 4-hydroxyimipramine (94436-87-0) + 1-hydroxyimipramine + 3-hydroxyimipramine

Conditions	Yield
With NADP+; D-glucose-6- In aq. phosphate buffer; dimethyl sulfoxide at 37℃; for 1h; pH=7.4; Enzymatic reaction;

Imipramine hydrochloride (113-52-0) + 2-hydroxynaphthalene-3-carboxylic acid sodium salt (14206-62-3, 37626-26-9, 40858-57-9, 85750-03-4) → imipramine xinafoate

Conditions	Yield
In water at 50℃; for 20h;	12.7 g

Imipramine hydrochloride (113-52-0) → impramine (50-49-7)

Conditions	Yield
With sodium hydroxide In water

C62H68N16O24S4(4-)*4Na(1+) + Imipramine hydrochloride (113-52-0) → C19H24N2*ClH*C62H68N16O24S4(4-)*4Na(1+)

Conditions	Yield
In aq. phosphate buffer pH=7.4; UV-irradiation;

Downstream Products

• 50-47-5 desipramine 
• 494-19-9 9,10-dihydrodibenzazepine 
• 796-28-1 10-Hydroxyimipramine 
• 303-70-8 2-hydroxyimipramine 
• 6829-98-7 imipramine N-oxide 
• 61361-33-9 C₁₉H₂₀⁽²⁾H₄N₂*ClH 
• 50-49-7 impramine 
• 10075-24-8 imipramine pamoate 
• 1085510-17-3 imipramine salicylate 

Related news

Aggregation behavior and interaction of an amphiphilic drug Imipramine hydrochloride (cas 113-52-0) with cationic surfactant cetyltrimethylammonium bromide: Light scattering studies08/28/2019

The aggregation behavior and interaction of an amphiphilic antidepressant drug imipramine (IMP) hydrochloride with the cationic surfactant cetyltrimethylammonium bromide (CTAB) have been studied using light scattering (both static and dynamic) techniques. Due to rigid tricyclic hydrophobic moiet...detailed

Imipramine hydrochloride (cas 113-52-0) and desipramine hydrochloride as new reagents for detection of microamounts of blood in urine08/27/2019

Benzidine and o-tolidine, the hazardous carcinogens are still in use for the detection of blood in urine. Development of safer substitutes are of paramount importance. Unfortunately, the alternate available reagents lack specificity, sensitivity and reproducibility. Imipramine hydrochloride (IPH...detailed

Role of various additives on the clouding phenomenon observed in Imipramine hydrochloride (cas 113-52-0) solutions08/26/2019

The effect of various additives used in pharmaceutical formulations (inorganic salts, QABs, amino acids, sugars, alcohols, ureas) has been seen by studying the clouding phenomenon of imipramine hydrochloride (IMP) drug in solution. At fixed pH values, increasing inorganic salt concentrations cau...detailed

Association behavior of a mixed system of the antidepressant drug Imipramine hydrochloride (cas 113-52-0) and dioctyl sulfosuccinate sodium salt: Effect of temperature and salt08/24/2019

Herein, we have checked the interaction between the imipramine hydrochloride (IMH, an antidepressant drug) and anionic surfactant dioctyl sulfosuccinate sodium salt (AOT) mixed system through a conductometric method in aqueous medium along with electrolyte solutions at different temperatures (28...detailed

Interaction of amphiphilic drug Imipramine hydrochloride (cas 113-52-0) with gemini surfactants at different temperatures08/23/2019

Imipramine hydrochloride (IMP) is a drug which is amphiphilic. Its interaction with gemini surfactants 14-s-14 (s = 4, 5, 6) has been investigated at different temperatures employing conductimetric measurements. The experimentally determined critical micelle concentration (cmc) values come out t...detailed

Effect of various cationic hydrotropes on association behaviour of Imipramine hydrochloride (cas 113-52-0) at different temperatures08/21/2019

The micellization phenomena in the mixed system of the amphiphilic antidepressant drug imipramine hydrochloride (IPH) and cationic hydrotropes - aniline hydrochloride (AnH), ortho-toluidine hydrochloride (o-ToH), as well as para-toluidine hydrochloride (p-ToH)- in a water solution at a range of ...detailed

Relevant academic research and scientific papers

POLYMORPHS OF IMIPRAMINE HYDROCHLORIDE AND PAMOATE SALT

The present invention relates to novel polymorphs of imipramine salts and the processes for their preparation.