QuickView for imipramine (compound)

Summary
General Info

PubChem

PubChem Compound 25379

Name:	Imipramine
PubChem Compound ID:	25379
Description:	The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group.
Molecular formula:	C₂₀H₂₆ClN
Molecular weight:	315.88 g/mol
Synonyms:	CHEBI:5882; LU 3-070; Antideprin hydrochloride; N,N-Dimethyl-10,11-dihydro-5H-dibenzo(a,d)cycloheptene-5-propylamine hydrochloride; 10563-68-5; VUFB2793; 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N,N-dimethylpropan-1-amine hydrochloride; Imipramine hydrochloride; 5H-DIBENZO(a,d)CYCLOHEPTENE-5-PROPYLAMINE, 10,11-DIHYDRO-N,N-DIMETHYL-, HYDROCHL; 5H-Dibenzo(a,d)cycloheptene-5-propylamine, 10,11-dihydro-N,N-dimethyl-, hydrochloride. show more » CHEBI:5882; LU 3-070; Antideprin hydrochloride; N,N-Dimethyl-10,11-dihydro-5H-dibenzo(a,d)cycloheptene-5-propylamine hydrochloride; 10563-68-5; VUFB2793; 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N,N-dimethylpropan-1-amine hydrochloride; Imipramine hydrochloride; 5H-DIBENZO(a,d)CYCLOHEPTENE-5-PROPYLAMINE, 10,11-DIHYDRO-N,N-DIMETHYL-, HYDROCHL; 5H-Dibenzo(a,d)cycloheptene-5-propylamine, 10,11-dihydro-N,N-dimethyl-, hydrochloride; 113-52-0; Tofranil show less «

DrugBank

Identification

Name:	Imipramine
Name (isomeric):	DB00458
Drug Type:	small molecule
Description:	The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group.
Brand:	Surplix, Prazepine, Tipramine, Presamine, Psychoforin, Intalpram, Iramil, Janimine, Antideprin, Imiprin, Tofranil-PM (imipramine pamoate), Sk-Pramine, Timolet, Melipramine, Impramine, Censtin, Imipramina, DPID, Censtim, Nelipramin, Eupramin, Tofraniln A, Imavate, Berkomine, Dynaprin, Norfranil, Trimipramine Maleate, Dyna-Zina, Imipramine Hcl, IM, Pramine, Dimipressin, Imidobenzyle, Imizin, Irmin, Imizine, Promiben, Estraldine, Imizinum, Declomipramine, Melipramin, Tofranil, Base
Category:	Norepinephrine-Reuptake Inhibitors, Adrenergic Uptake Inhibitors, Antidepressive Agents, Tricyclic
CAS number:	50-49-7

Pharmacology

Indication:	For the relief of symptoms of depression and as temporary adjunctive therapy in reducing enuresis in children aged 6 years and older. May also be used to manage panic disorders, with or without agoraphobia, as a second line agent in ADHD, management of eating disorders, for short-term management of acute depressive episodes in bipolar disorder and schizophrenia, and for symptomatic treatment of postherpetic neuralgia.
Pharmacology:	Imipramine is a tricyclic antidepressant with general pharmacological properties similar to those of structurally related tricyclic antidepressant drugs such as amitriptyline and doxepin. A tertiary amine, imipramine inhibits the reuptake of serotonin more so than most secondary amine tricyclics, meaning that it blocks the reuptake of neurotransmit... show more » Imipramine is a tricyclic antidepressant with general pharmacological properties similar to those of structurally related tricyclic antidepressant drugs such as amitriptyline and doxepin. A tertiary amine, imipramine inhibits the reuptake of serotonin more so than most secondary amine tricyclics, meaning that it blocks the reuptake of neurotransmitters serotonin and noradrenaline almost equally. With chronic use, imipramine also down-regulates cerebral cortical β-adrenergic receptors and sensitizes post-synaptic sertonergic receptors, which also contributes to increased serotonergic transmission. It takes approximately 2 - 4 weeks for antidepressants effects to occur. The onset of action may be longer, up to 8 weeks, in some individuals. It is also effective in migraine prophylaxis, but not in abortion of acute migraine attack. show less «
Mechanism of Action:	Imipramine works by inhibiting the neuronal reuptake of the neurotransmitters norepinephrine and serotonin. It binds the sodium-dependent serotonin transporter and sodium-dependent norepinephrine transporter preventing or reducing the reuptake of norepinephrine and serotonin by nerve cells. Depression has been linked to a lack of stimulation of the... show more » Imipramine works by inhibiting the neuronal reuptake of the neurotransmitters norepinephrine and serotonin. It binds the sodium-dependent serotonin transporter and sodium-dependent norepinephrine transporter preventing or reducing the reuptake of norepinephrine and serotonin by nerve cells. Depression has been linked to a lack of stimulation of the post-synaptic neuron by norepinephrine and serotonin. Slowing the reuptake of these neurotransmitters increases their concentration in the synaptic cleft, which is thought to contribute to relieving symptoms of depression. In addition to acutely inhibiting neurotransmitter re-uptake, imipramine causes down-regulation of cerebral cortical beta-adrenergic receptors and sensitization of post-synaptic serotonergic receptors with chronic use. This leads to enhanced serotonergic transmission. show less «
Absorption:	Rapidly and well absorbed after oral administration. Bioavailability is approximately 43%. Peak plasma concentrations usually attained 1 - 2 hours following oral administration. Absorption is unaffected by food.
Protein binding:	60-95%
Biotransformation:	Exclusively metabolized by the liver. Imipramine is converted in the liver by various CYP isoenzymes (e.g. CYP1A2, CYP2D6, CYP3A4, CYP2C9) to active metabolites desipramine and 2-hydroxydesipramine.
Route of elimination:	Approximately 40% of an orally administered dose is eliminated in urine within 24 hours, 70% in 72 hours. Small amounts are eliminated in feces via the biliary elimination.
Half Life:	Imipramine - 8-20 hours; Desipramine (active metabolite) - up to 125 hours
Toxicity:	Oral, rat LD₅₀: 355 to 682 mg/kg. Toxic signs proceed progressively from depression, irregular respiration and ataxia to convulsions and death. Antagonism of the histamine H₁ and α₁ receptors can lead to sedation and hypotension. Antimuscarinic and anticholinergic side effects such as blurred vision, dry mouth, constipation and urine retention may occur. Cardiotoxicity may occur with high doses of imipramine. Cardiovascular side effects in postural hypotension, tachycardia, hypertension, ECG changes and congestive heart failure. Psychotoxic effects include impaired memory and delirium. Induction of hypomanic or manic episodes may occur in patients with a history of bipolar disorder. Withdrawal symptoms include GI disturbances (e.g. nausea, vomiting, abdominal pain, diarrhea), anxiety, insomnia, nervousness, headache and malaise.
Affected organisms:	Humans and other mammals

Interactions

Food interaction:

Avoid St.John's Wort.

Avoid alcohol.

Avoid excessive quantities of coffee or tea (caffeine).

Do not take fibers at the same time.

Take with food.

Drug interaction:

Grepafloxacin	Increased risk of cardiotoxicity and arrhythmias
Tacrine	The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Imipramine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Duloxetine	Possible increase in the levels of this agent when used with duloxetine
Rifabutin	The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, imipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of imipramine if rifabutin is initiated, discontinued or dose changed.
Sparfloxacin	Increased risk of cardiotoxicity and arrhythmias

Grepafloxacin	Increased risk of cardiotoxicity and arrhythmias
Tacrine	The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Imipramine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Duloxetine	Possible increase in the levels of this agent when used with duloxetine
Rifabutin	The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, imipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of imipramine if rifabutin is initiated, discontinued or dose changed.
Sparfloxacin	Increased risk of cardiotoxicity and arrhythmias
Phenylephrine	The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of phenylephrine.
Zolmitriptan	Use of two serotonin modulators, such as zolmitriptan and imipramine, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
Tranylcypromine	Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.
Lumefantrine	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Ephedrine	The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of ephedrine.
Butalbital	Barbiturates such as butalbital may increase the metabolism of tricyclic antidepressants such as imipramine. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
Pirbuterol	The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of pirbuterol.
Trazodone	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Phenelzine	Possibility of severe adverse effects
Trospium	Trospium and Imipramine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Thioridazine	Increased risk of cardiotoxicity and arrhythmias
Epinephrine	The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of epinephrine.
Procaterol	The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of procaterol.
Moclobemide	Possible severe adverse reaction with this combination
Galantamine	Possible antagonism of action
Clonidine	The tricyclic antidepressant, imipramine, decreases the effect of clonidine.
Metaraminol	The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of metaraminol.
Artemether	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Tamsulosin	Imipramine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Imipramine is initiated, discontinued, or dose changed.
Tacrolimus	Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Methoxamine	The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of methoxamine.
Toremifene	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Isocarboxazid	Possibility of severe adverse effects
Orciprenaline	The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of orciprenaline.
Rivastigmine	Possible antagonism of action
Quinidine barbiturate	Quinidine barbiturate increases the effect of tricyclic antidepressant, imipramine.
Voriconazole	Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Fluconazole	Fluconazole may increase the effect and toxicity of the tricyclic antidepressant, imipramine, by decreasing its metabolism. Additive QTc-prolonging effects may also occur. Monitor for changes in the therapeutic and adverse effects of imipramine if fluconazole is initiated, discontinued or dose changed. Monitor for the development of torsades de pointes during concomitant therapy.
Trimipramine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Sibutramine	Increased risk of CNS adverse effects
Terbinafine	Terbinafine may increase the effect and toxicity of the tricyclic antidepressant, imipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of imipramine if terbinafine is initiated, discontinued or dose changed.
Dihydroquinidine barbiturate	Dihydroquinidine barbiturate increases the effect of the tricyclic antidepressant, imipramine.
Norepinephrine	The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of norepinephrine.
Quinidine	Additive QTc-prolonging effects may occur. Quinidine may also increase the serum concentration of the tricyclic antidepressant, imipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of imipramine if quinidine is initiated, discontinued or dose changed. Monitor for the development of torsades de pointes during concomitant therapy.
Rifampin	The rifamycin, rifampin, may decrease the effect of the tricyclic antidepressant, imipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of imipramine if rifampin is initiated, discontinued or dose changed.
Tramadol	Tramadol increases the risk of serotonin syndrome and seizures. Imipramine may decrease the effect of Tramadol by decreasing active metabolite production.
Dopamine	The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of dopamine.
Venlafaxine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Tamoxifen	Imipramine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
Dobutamine	The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of dobutamine.
Terbutaline	The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of terbutaline.
Donepezil	Possible antagonism of action
Mephentermine	The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of mephentermine.
Zuclopenthixol	Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Guanethidine	The tricyclic antidepressant, imipramine, may increase the sympathomimetic effect of guanethidine.
Altretamine	Risk of severe hypotension
Trimethobenzamide	Trimethobenzamide and Imipramine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Carbamazepine	Carbamazepine may decrease the serum concentration of the tricyclic antidepressant, imipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of imipramine if carbamazepine is initiated, discontinued or dose changed.
Desvenlafaxine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Ketoconazole	Ketoconazole, a moderate CYP2D6 inhibitor, may increase the serum concentration of imipramine by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of imipramine if ketoconazole is initiated, discontinued or dose changed.
Mesoridazine	Increased risk of cardiotoxicity and arrhythmias
Fluoxetine	The SSRI, fluoxetine, may increase the serum concentration of the tricyclic antidepressant, imipramine, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of imipramine if fluoxetine is initiated, discontinued or dose changed.
Cimetidine	Cimetidine may increase the effect of the tricyclic antidepressant, imipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of imipramine if cimetidine is initiated, discontinued or dose changed.
Thiothixene	May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
Vorinostat	Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Terfenadine	Increased risk of cardiotoxicity and arrhythmias
Ephedra	The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of ephedra.
Ticlopidine	Ticlopidine may decrease the metabolism and clearance of Imipramine. Consider alternate therapy or monitor for adverse/toxic effects of Imipramine if Ticlopidine is initiated, discontinued or dose changed.
Phenylpropanolamine	The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of phenylpropanolamine.
Atazanavir	Atazanavir may increase the effect and toxicity of the tricyclic antidepressant, imipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of imipramine if atazanavir if initiated, discontinued or dose changed.
Butabarbital	Barbiturates like butabarbital may increase the metabolism of tricyclic antidepressants like imipramine. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
Isoproterenol	The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of isoproterenol.
Ziprasidone	Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
Triprolidine	Triprolidine and Imipramine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
Salbutamol	The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of salbutamol.
Fluvoxamine	The SSRI, fluvoxamine, may increase the serum concentration of the tricyclic antidepressant, imipramine, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of imipramine if fluvoxamine is initiated, discontinued or dose changed.
Ritonavir	Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, imipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of imipramine if ritonavir if initiated, discontinued or dose changed.
Pseudoephedrine	The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of pseudoephedrine.
Fenoterol	The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of fenoterol.
Cisapride	Increased risk of cardiotoxicity and arrhythmias
Rasagiline	Possibility of severe adverse effects