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

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 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
Low dose desipramine treatment of cocaine-related panic attacks.	1991 Dec	1744635
Low dose tricyclic tachycardia.	1991 Jan	1810269
Changes in convulsion susceptibility of lidocaine by alteration of brain catecholaminergic functions.	1991 May	1880990
Oral contraceptives and panic disorder.	1992 May	1592843
Effect of IAP and chronic antidepressant administration on the 5HT1A receptor in rat cortical membranes.	1992 May	1589591
Desipramine in opioid-dependent cocaine abusers maintained on buprenorphine vs methadone.	1999 Sep	12884887
Effect of tolcapone on the haemodynamic effects and tolerability of desipramine.	2000	10965161
Antidepressant drugs appear to enhance cocaine-induced toxicity.	2000 Feb	10743914
Modifications in brain CaM kinase II after long-term treatment with desmethylimipramine.	2001 Jan	11106872
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
Utility of crossover designs in clinical trials: efficacy of desipramine vs. placebo in opioid-dependent cocaine abusers.	2002 Spring	12028741
Comorbid major depressive disorder as a prognostic factor in cocaine-abusing buprenorphine-maintained patients treated with desipramine and contingency management.	2003 Aug	14510037
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
[Effects of neurotensin microinjected into ventral tegmental area on spontaneous motor activity in neonatal 6-hydroxydopamine-treated rats].	2004 Apr	15164616
Ethnic differences in substance abuse treatment retention, compliance, and outcome from two clinical trials.	2004 Feb	14762242
Clinical implications of genetic polymorphism of CYP2D6 in Mexican Americans.	2004 Jun 1	15172931
Norepinephrine-deficient mice lack responses to antidepressant drugs, including selective serotonin reuptake inhibitors.	2004 May 25	15148402
Inhibition of G protein-activated inwardly rectifying K+ channels by various antidepressant drugs.	2004 Oct	15150531
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
Desipramine treatment for cocaine dependence in buprenorphine- or methadone-treated patients: baseline urine results as predictor of response.	2005 Jan-Feb	15804873
Interferon-alpha-induced modulation of glucocorticoid and serotonin receptors as a mechanism of depression.	2005 Jun	15885359
Brugada syndrome precipitated by a tricyclic antidepressant.	2005 May	15831654
Selective cortical VGLUT1 increase as a marker for antidepressant activity.	2005 Nov	16111724
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
A selective test for antidepressant treatments using rats bred for stress-induced reduction of motor activity in the swim test.	2005 Oct	16047194
The effects of desmethylimipramine on cyclic AMP-stimulated gene transcription in a model cell system.	2005 Sep 1	16036225
Nigrostriatal damage with 6-OHDA: validation of routinely applied procedures.	2006 Aug	17105931
[Trazodone for the treatment of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease: a retrospective study focused on the aggression and negativism in caregiving situations].	2006 Jun	16856516
Down-regulation of norepinephrine transporter function induced by chronic administration of desipramine linking to the alteration of sensitivity of local-anesthetics-induced convulsions and the counteraction by co-administration with local anesthetics.	2006 Jun 22	16725121
Pharmacokinetics of desipramine HCl when administered with cinacalcet HCl.	2007 Feb	16680561
CRE/CREB-driven up-regulation of gene expression by chronic social stress in CRE-luciferase transgenic mice: reversal by antidepressant treatment.	2007 May 9	17487276
The role of NMDA receptor antagonists in nicotine tolerance, sensitization, and physical dependence: a preclinical review.	2008 Apr 30	18452252
Narcolepsy: current treatment options and future approaches.	2008 Jun	18830438
Evaluation of the repeated open-space swim model of depression in the mouse.	2008 Nov	18692087
Community-based randomised controlled trial evaluating falls and osteoporosis risk management strategies.	2008 Nov 4	18983670
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
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
Antidepressants influence somatostatin levels and receptor pharmacology in brain.	2009 Mar	18800063
Association of changes in norepinephrine and serotonin transporter expression with the long-term behavioral effects of antidepressant drugs.	2009 May	18923402
MPTP-induced neuroblast apoptosis in the subventricular zone is not regulated by dopamine or other monoamine transporters.	2009 Nov	19616025
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.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:16:05 GMT 2023` Edited by `admin` on `Fri Dec 15 15:16:05 GMT 2023`
Record UNII	TG537D343B
Record Status	`Validated (UNII)`
Record Version

Download

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