DESIPRAMINE HYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C18H22N2.ClH
Molecular Weight	302.842
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CNCCCN1C2=CC=CC=C2CCC3=CC=CC=C13

InChI

InChIKey=XAEWZDYWZHIUCT-UHFFFAOYSA-N

InChI=1S/C18H22N2.ClH/c1-19-13-6-14-20-17-9-4-2-7-15(17)11-12-16-8-3-5-10-18(16)20;/h2-5,7-10,19H,6,11-14H2,1H3;1H

HIDE SMILES / InChI

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C18H22N2
Molecular Weight	266.3807
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/014399s066s067lbl.pdf | https://www.drugbank.ca/drugs/DB01151 | http://americanaddictioncenters.org/addiction-medications/desipramine/

Desipramine is a tricyclic antidepressant that was approved by the FDA in 1964. It was derived from imipramine, which was the first tricyclic antidepressant to be manufactured. Desipramine is one of many tricyclic antidepressants, and this type of antidepressant gets its name due to its three-ring chemical structure. Desipramine, a secondary amine tricyclic antidepressant, is structurally related to both the skeletal muscle relaxant cyclobenzaprine and the thioxanthene antipsychotics such as thiothixene. It is the active metabolite of imipramine, a tertiary amine TCA. The acute effects of desipramine include inhibition of noradrenaline re-uptake at noradrenergic nerve endings and inhibition of serotonin (5-hydroxy tryptamine, 5HT) re-uptake at the serotoninergic nerve endings in the central nervous system. Desipramine exhibits greater noradrenergic re-uptake inhibition compared to the tertiary amine TCA imipramine. In addition to inhibiting neurotransmitter re-uptake, desipramine down-regulates beta-adrenergic receptors in the cerebral cortex and sensitizes serotonergic receptors with chronic use. The overall effect is increased serotonergic transmission. Antidepressant effects are typically observed 2 - 4 weeks following the onset of therapy though some patients may require up to 8 weeks of therapy prior to symptom improvement. Patients experiencing more severe depressive episodes may respond quicker than those with mild depressive symptoms. Desipramine is marketed under the trade name Norpramin, indicated for the treatment of depression.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Norepinephrine transporter 197 Target ID: CHEMBL222 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/014399s066s067lbl.pdf	Inhibitor 8504	1.5 nM [IC50]
Serotonin transporter 183 Target ID: CHEMBL228 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/014399s066s067lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/9400006 \| https://www.ncbi.nlm.nih.gov/pubmed/17690258	Inhibitor 8504	163.0 nM [Ki]
Serotonin 2a (5-HT2a) receptor 237 Target ID: CHEMBL224 Sources: https://www.drugbank.ca/drugs/DB01151	Antagonist 2849

Conditions

Condition	Modality	Targets	Highest Phase	Product
Depression 240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/014399s066s067lbl.pdf	Primary		Approved 8583	NORPRAMIN Approved Use Desipramine hydrochloride tablets are indicated for the treatment of depression. Launch Date 1964

C_max

Value	Dose	Co-administered	Analyte	Population
21.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16680561	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		DESIPRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
656 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16680561	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		DESIPRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
21 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16680561	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		DESIPRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
9.78% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4386616			DESIPRAMINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
2500 mg single, oral Overdose Dose: 2500 mg Route: oral Route: single Dose: 2500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/5588337	healthy, 2 years Health Status: healthy Age Group: 2 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/5588337	Other AEs: Coma, Seizures... Other AEs: Coma (grade 5, 1 patient) Seizures (grade 5, 1 patient) Hypotension (grade 5, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/5588337
300 mg 1 times / day multiple, oral Highest studied dose Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/32413603	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://pubmed.ncbi.nlm.nih.gov/32413603	Sources: https://pubmed.ncbi.nlm.nih.gov/32413603
25 mg 1 times / day multiple, oral Recommended Dose: 25 mg, 1 times / day Route: oral Route: multiple Dose: 25 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/014399s071lbl.pdf	unhealthy, children \| adolescents \| and young adults Health Status: unhealthy Age Group: children \| adolescents \| and young adults Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/014399s071lbl.pdf	Other AEs: Suicidal ideation... Other AEs: Suicidal ideation Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/014399s071lbl.pdf

AEs

AE	Significance	Dose	Population
Coma	grade 5, 1 patient	2500 mg single, oral Overdose Dose: 2500 mg Route: oral Route: single Dose: 2500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/5588337	healthy, 2 years Health Status: healthy Age Group: 2 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/5588337
Hypotension	grade 5, 1 patient	2500 mg single, oral Overdose Dose: 2500 mg Route: oral Route: single Dose: 2500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/5588337	healthy, 2 years Health Status: healthy Age Group: 2 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/5588337
Seizures	grade 5, 1 patient	2500 mg single, oral Overdose Dose: 2500 mg Route: oral Route: single Dose: 2500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/5588337	healthy, 2 years Health Status: healthy Age Group: 2 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/5588337
Suicidal ideation		25 mg 1 times / day multiple, oral Recommended Dose: 25 mg, 1 times / day Route: oral Route: multiple Dose: 25 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/014399s071lbl.pdf	unhealthy, children \| adolescents \| and young adults Health Status: unhealthy Age Group: children \| adolescents \| and young adults Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/014399s071lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	substrate 1388 inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2C19 2057 OCT3 159 MATE1 415 MATE2 267 OCT2 779

Drug as perpetrator

Target	Modality	Activity
OCT2 782	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/9260930/	yes [IC50 16 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291266/	yes [Inhibition 20 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291266/	yes [Inhibition 20 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291266/	yes [Inhibition 20 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291266/	yes [Inhibition 20 uM]
OCT3 161	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/10966924/	yes [Ki 14 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1381398/pdf/brjclinpharm00042-0080.pdf#page=2 Page: 2.0	yes [Ki 2.3 uM]
MATE2 267	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/19164462/	yes [Ki 283 uM]
MATE1 416	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/19164462/	yes [Ki 55.7 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/9758674/	yes		no (co-administration study) Comment: Ketoconazole did not alter the pharmacokinetics of orally administered desipramine in healthy volunteers; Genetic deficiency in CYP2D6 activity results in a 85% lower oral clearance of desipramine, as shown by a single dose pharmacokinetic study in healthy volunteers Sources: https://pubmed.ncbi.nlm.nih.gov/9758674/

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubmed.ncbi.nlm.nih.gov/21120454/ Page: 11.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:47781	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:47781
eMolecules	1883445	https://www.emolecules.com/cgi-bin/more?vid=1883445
MolPort	MolPort-002-051-955	https://www.molport.com/shop/molecule-link/MolPort-002-051-955
ZINC	ZINC000001530611	http://zinc15.docking.org/substances/ZINC000001530611

PubMed

Title	Date	PubMed
Ascending catecholamine pathways and amphetamine-induced locomotor activity: importance of dopamine and apparent non-involvement of norepinephrine.	1975 Aug 15	1236760
Low dose tricyclic tachycardia.	1991 Jan	1810269
Repeated administration of desmethylimipramine blocks the reserpine-induced increase in tyrosine hydroxylase mRNA in locus coeruleus neurons of the rat.	1991 Jul	1717808
Regulation of serotonin type 2 (5-HT2) and beta-adrenergic receptors in rat cerebral cortex following novel and classical antidepressant treatment.	1991 Nov	1664741
Desipramine-induced oral-pharyngeal disturbances: stuttering and jaw myoclonus.	1992 Dec	1474184
Increased pulse and blood pressure associated with desipramine treatment of bulimia nervosa.	1992 Jun	1629381
Oral contraceptives and panic disorder.	1992 May	1592843
Trazodone induction of migraine headache through mCPP.	1992 May	1575270
Activity of phenothiazines against antibiotic-resistant Mycobacterium tuberculosis: a review supporting further studies that may elucidate the potential use of thioridazine as anti-tuberculosis therapy.	2001 May	11328759
Microheterogeneity of myocardial blood flow.	2001 Nov	11770072
Antidepressants reduce phosphoinositide-specific phospholipase C (PI-PLC) activity and the mRNA and protein expression of selective PLC beta 1 isozyme in rat brain.	2002 Dec	12527476
Acute treatment with the cyclic antidepressant desipramine, but not fluoxetine, increases membrane-associated G protein-coupled receptor kinases 2/3 in rat brain.	2002 Dec	12527474
Effects of catecholamine uptake blockers in the caudate-putamen and subregions of the medial prefrontal cortex of the rat.	2002 May 17	11988230
Chronic inhibition of the norepinephrine transporter in the brain participates in seizure sensitization to cocaine and local anesthetics.	2003 Feb 21	12573515
Desipramine and contingency management for cocaine and opiate dependence in buprenorphine maintained patients.	2003 Jun 5	12757969
NO induced apoptosis of vascular smooth muscle cells accompanied by ceramide increase.	2004 May	15040013
Norepinephrine-deficient mice lack responses to antidepressant drugs, including selective serotonin reuptake inhibitors.	2004 May 25	15148402
Evaluation of fresh and cryopreserved hepatocytes as in vitro drug metabolism tools for the prediction of metabolic clearance.	2004 Nov	15286053
Desipramine treatment for cocaine dependence in buprenorphine- or methadone-treated patients: baseline urine results as predictor of response.	2005 Jan-Feb	15804873
Brugada syndrome precipitated by a tricyclic antidepressant.	2005 May	15831654
Desipramine treatment of cocaine-dependent patients with depression: a placebo-controlled trial.	2005 Nov 1	15913920
Nigrostriatal damage with 6-OHDA: validation of routinely applied procedures.	2006 Aug	17105931
Response to SSRI-induced enuresis: a case report.	2006 Feb	16415720
Frequency of high-risk use of QT-prolonging medications.	2006 Jun	16178046
Reduced evoked fos expression in activity-related brain regions in animal models of behavioral depression.	2007 Aug 15	17513031
Desipramine activated Bcl-2 expression and inhibited lipopolysaccharide-induced apoptosis in hippocampus-derived adult neural stem cells.	2007 May	17510525
Desipramine induces apoptotic cell death through nonmitochondrial and mitochondrial pathways in different types of human colon carcinoma cells.	2008	18025841
The role of NMDA receptor antagonists in nicotine tolerance, sensitization, and physical dependence: a preclinical review.	2008 Apr 30	18452252
Desipramine-induced apoptosis in human PC3 prostate cancer cells: activation of JNK kinase and caspase-3 pathways and a protective role of [Ca2+]i elevation.	2008 Aug 19	18606486
Comparison of the effects of desmethylimipramine on behavior in the forced swim test in peripubertal and adult rats.	2008 Feb	18195598
Evaluation of the repeated open-space swim model of depression in the mouse.	2008 Nov	18692087
Desipramine potentiation of the acute depressant effects of ethanol: modulation by alpha2-adrenoreceptors and stress.	2008 Oct	18625256
Neuronal damage and protection in the pathophysiology and treatment of psychiatric illness: stress and depression.	2009	19877493
Tetrabenazine as anti-chorea therapy in Huntington disease: an open-label continuation study. Huntington Study Group/TETRA-HD Investigators.	2009 Dec 18	20021666
Behavioral sensitization to cocaine: cooperation between glucocorticoids and epinephrine.	2009 Jul	19266184
Reactivation of inflammatory bowel disease in a mouse model of depression.	2009 Jun	19272381
Transient supersensitivity to alpha-adrenoceptor agonists, and distinct hyper-reactivity to vasopressin and angiotensin II after denervation of rat tail artery.	2010 Jan	20002103

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Depression 100 to 200 mg orally per day Maximum dose: 300 mg orally per day Comments: -Dosage should be initiated at a lower level and increased according to tolerance and clinical response. -In severely ill patients, dosage may be further increased to 300 mg per day if needed. -Treatment of patients requiring as much as 300 mg should generally be initiated in hospitals. Usual Geriatric Dose for Depression 25 to 100 mg orally per day Maximum dose: 150 mg orally per day

Route of Administration: Oral

In Vitro Use Guide

Neuronal uptake 1 inhibitor desipramine (100 nM) decreased NE in 60-min hypothermic ischemia in isolated perfused guinea pig hearts.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 17:52:51 GMT 2025` Edited by `admin` on `Mon Mar 31 17:52:51 GMT 2025`
Record UNII	1Y58DO4MY1
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DESIPRAMINE HYDROCHLORIDE

Official Name

English

NORPRAMIN

Preferred Name

English

DESIPRAMINE HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

RMI 9,384A

Code

English

RMI-9384A

Code

English

5H-DIBENZ(B,F)AZEPINE-5-PROPANAMINE, 10,11-DIHYDRO-N-METHYL-, MONOHYDROCHLORIDE

Common Name

English

JB-8181

Code

English

Desipramine hydrochloride [WHO-DD]

Common Name

English

EX-4355

Code

English

DESIPRAMINE HYDROCHLORIDE [USP MONOGRAPH]

Common Name

English

PERTOFRANE

Brand Name

English

EX 4355

Code

English

DESIPRAMINE HYDROCHLORIDE [MI]

Common Name

English

NSC-114901

Code

English

DESIPRAMINE HCL

Common Name

English

DESIPRAMINE HYDROCHLORIDE [USP-RS]

Common Name

English

DESIPRAMINE HYDROCHLORIDE [EP MONOGRAPH]

Common Name

English

G-35020

Code

English

10,11-DIHYDRO-5-(3-(METHYLAMINO)PROPYL)-5H-DIBENZ(B,F)AZEPINE MONOHYDROCHLORIDE

Systematic Name

English

DESIPRAMINE HYDROCHLORIDE [MART.]

Common Name

English

DMI

Common Name

English

DESIPRAMINE HYDROCHLORIDE [USAN]

Common Name

English

DESIPRAMINE HYDROCHLORIDE [VANDF]

Common Name

English

DESIPRAMINE HYDROCHLORIDE [JAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C94727