DESIPRAMINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C18H22N2
Molecular Weight	266.3807
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CNCCCN1C2=C(CCC3=C1C=CC=C3)C=CC=C2

InChI

InChIKey=HCYAFALTSJYZDH-UHFFFAOYSA-N

InChI=1S/C18H22N2/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

HIDE SMILES / InChI

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 191 Target ID: CHEMBL222 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/014399s066s067lbl.pdf	Inhibitor 8297	1.5 nM [IC50]
Serotonin transporter 178 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 8297	163.0 nM [Ki]
Serotonin 2a (5-HT2a) receptor 231 Target ID: CHEMBL224 Sources: https://www.drugbank.ca/drugs/DB01151	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Depression 235 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/014399s066s067lbl.pdf	Primary		Approved 8429	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 n = 1 Health Status: healthy Age Group: 2 years Sex: F Population Size: 1 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 n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 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 Condition: major depressive disorde 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 n = 1 Health Status: healthy Age Group: 2 years Sex: F Population Size: 1 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 n = 1 Health Status: healthy Age Group: 2 years Sex: F Population Size: 1 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 n = 1 Health Status: healthy Age Group: 2 years Sex: F Population Size: 1 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 Condition: major depressive disorde 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 1587	inhibitor 1767	substrate 1217 inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2C19 1478 OCT3 150 MATE1 306 MATE2 263 OCT2 647

Drug as perpetrator

Target	Modality	Activity
OCT2 648	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/9260930/	yes [IC50 16 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291266/	yes [Inhibition 20 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291266/	yes [Inhibition 20 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291266/	yes [Inhibition 20 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291266/	yes [Inhibition 20 uM]
OCT3 150	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10966924/	yes [Ki 14 uM]
CYP2D6 1891	inhibitor 3277 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 263	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19164462/	yes [Ki 283 uM]
MATE1 308	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19164462/	yes [Ki 55.7 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 1217	substrate 3367 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 1647	inhibitor 1626 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
MolPort	MolPort-002-051-955	https://www.molport.com/shop/molecule-link/MolPort-002-051-955
ZINC	ZINC000001530611	http://zinc15.docking.org/substances/ZINC000001530611
eMolecules	1883445	https://www.emolecules.com/cgi-bin/more?vid=1883445

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 desipramine treatment of cocaine-related panic attacks.	1991 Dec	1744635
Low dose tricyclic tachycardia.	1991 Jan	1810269
Regulation of serotonin type 2 (5-HT2) and beta-adrenergic receptors in rat cerebral cortex following novel and classical antidepressant treatment.	1991 Nov	1664741
Control of depression with fluoxetine and antiseizure medication in a brain-injured patient.	1992 Feb	1734754
Increased pulse and blood pressure associated with desipramine treatment of bulimia nervosa.	1992 Jun	1629381
Reversal of desipramine toxicity in rats using drug-specific antibody Fab' fragment: effects on hypotension and interaction with sodium bicarbonate.	1992 Mar	1312169
Oral contraceptives and panic disorder.	1992 May	1592843
Trazodone induction of migraine headache through mCPP.	1992 May	1575270
Bupropion-induced carbohydrate craving and weight gain.	1992 Oct	1530081
National Patterns of Medication Treatment for Depression, 1987 to 2001.	2001 Dec	15014590
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
Tricyclic antidepressants and the Brugada syndrome: an example of Brugada waves appearing after the administration of desipramine.	2002 Aug	12173907
[Effect of local and systemic desipramine administration on extracellular noradrenaline in the myocardium of rats].	2002 Dec	12852214
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
Utility of crossover designs in clinical trials: efficacy of desipramine vs. placebo in opioid-dependent cocaine abusers.	2002 Spring	12028741
Prediction of treatment outcome by baseline urine cocaine results and self-reported cocaine use for cocaine and opioid dependence.	2003	14713135
Chronic inhibition of the norepinephrine transporter in the brain participates in seizure sensitization to cocaine and local anesthetics.	2003 Feb 21	12573515
Chronic treatment with desipramine and fluoxetine modulate BDNF, CaMKKalpha and CaMKKbeta mRNA levels in the hippocampus of transgenic mice expressing antisense RNA against the glucocorticoid receptor.	2004 Dec	15555640
NO induced apoptosis of vascular smooth muscle cells accompanied by ceramide increase.	2004 May	15040013
Evaluation of fresh and cryopreserved hepatocytes as in vitro drug metabolism tools for the prediction of metabolic clearance.	2004 Nov	15286053
Brain-derived tumor necrosis factor-alpha and its involvement in noradrenergic neuron functioning involved in the mechanism of action of an antidepressant.	2004 Sep	15082752
Reboxetine for the treatment of patients with Cocaine Dependence Disorder.	2005 Apr	15799010
Blood pressure changes associated with medication treatment of adults with attention-deficit/hyperactivity disorder.	2005 Feb	15705013
Desipramine treatment for cocaine dependence in buprenorphine- or methadone-treated patients: baseline urine results as predictor of response.	2005 Jan-Feb	15804873
Coadministration of histone deacetylase inhibitors and perifosine synergistically induces apoptosis in human leukemia cells through Akt and ERK1/2 inactivation and the generation of ceramide and reactive oxygen species.	2005 Mar 15	15781658
Interaction of organic cations with a newly identified plasma membrane monoamine transporter.	2005 Nov	16099839
Desipramine treatment of cocaine-dependent patients with depression: a placebo-controlled trial.	2005 Nov 1	15913920
The effects of desmethylimipramine on cyclic AMP-stimulated gene transcription in a model cell system.	2005 Sep 1	16036225
Desipramine activated Bcl-2 expression and inhibited lipopolysaccharide-induced apoptosis in hippocampus-derived adult neural stem cells.	2007 May	17510525
Reduction of high-affinity beta2-adrenergic receptor binding by hyperforin and hyperoside on rat C6 glioblastoma cells measured by fluorescence correlation spectroscopy.	2007 May 1	17417877
A possible role for the endocannabinoid system in the neurobiology of depression.	2007 Nov 19	18021439
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
Comparison of the effects of desmethylimipramine on behavior in the forced swim test in peripubertal and adult rats.	2008 Feb	18195598
Photophysics and photochemistry of imipramine, desimipramine, and clomipramine in several solvents: a fluorescence, 266 nm laser flash, and theoretical study.	2008 Jan 10	18085762
Narcolepsy: current treatment options and future approaches.	2008 Jun	18830438
Impaired parasympathetic function increases susceptibility to inflammatory bowel disease in a mouse model of depression.	2008 Jun	18451995
Glucagon-like peptide 1 receptor stimulation reverses key deficits in distinct rodent models of Parkinson's disease.	2008 May 21	18492290
Community-based randomised controlled trial evaluating falls and osteoporosis risk management strategies.	2008 Nov 4	18983670
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
Desipramine-induced Ca-independent apoptosis in Mg63 human osteosarcoma cells: dependence on P38 mitogen-activated protein kinase-regulated activation of caspase 3.	2009 Mar	18986328
Association of changes in norepinephrine and serotonin transporter expression with the long-term behavioral effects of antidepressant drugs.	2009 May	18923402
Time course and dose response of alpha tocopherol on oxidative stress in haemodialysis patients.	2009 Oct 22	19845969
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.

Name

Type

Language

DESIPRAMINE

Official Name

English

Desipramine [WHO-DD]

Common Name

English

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

Systematic Name

English

N-DESMETHYLIMIPRAMINE

Common Name

English

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

Systematic Name

English

DESIPRAMINE [VANDF]

Common Name

English

DESIPRAMINE [HSDB]

Common Name

English

IMIPRAMINE, DEMETHYL-

Common Name

English

MONODEMETHYLIMIPRAMINE

Common Name

English

IMIPRAMINE HYDROCHLORIDE IMPURITY A [EP IMPURITY]

Common Name

English

desipramine [INN]

Common Name

English

NORIMIPRAMINE

Common Name

English

DESIPRAMINE [MI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C94727