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 183 Target ID: CHEMBL222 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/014399s066s067lbl.pdf	Inhibitor 8146	1.5 nM [IC50]
Serotonin transporter 172 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 8146	163.0 nM [Ki]
Serotonin 2a (5-HT2a) receptor 229 Target ID: CHEMBL224 Sources: https://www.drugbank.ca/drugs/DB01151	Antagonist 2737

Conditions

Condition	Modality	Targets	Highest Phase	Product
Depression 232 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/014399s066s067lbl.pdf	Primary		Approved 8307	NORPRAMIN Approved Use Desipramine hydrochloride tablets are indicated for the treatment of depression. Launch Date -1.61395196E11

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 1532	inhibitor 1695	substrate 1168 inhibitor 1789	inhibitor 1570

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1463 CYP2C19 1410 OCT3 143 MATE1 302 MATE2 259 OCT2 630

Drug as perpetrator

Target	Modality	Activity
OCT2 631	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/9260930/	yes [IC50 16 uM]
CYP1A2 1620	inhibitor 3185 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291266/	yes [Inhibition 20 uM]
CYP2C19 1484	inhibitor 3185 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291266/	yes [Inhibition 20 uM]
CYP2C9 1747	inhibitor 3185 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291266/	yes [Inhibition 20 uM]
CYP3A4 1857	inhibitor 3185 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291266/	yes [Inhibition 20 uM]
OCT3 143	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/10966924/	yes [Ki 14 uM]
CYP2D6 1826	inhibitor 3185 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 259	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/19164462/	yes [Ki 283 uM]
MATE1 304	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/19164462/	yes [Ki 55.7 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 1168	substrate 3264 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 1603	inhibitor 1584 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
Desipramine-induced oral-pharyngeal disturbances: stuttering and jaw myoclonus.	1992 Dec	1474184
Control of depression with fluoxetine and antiseizure medication in a brain-injured patient.	1992 Feb	1734754
Oral contraceptives and panic disorder.	1992 May	1592843
Desipramine in opioid-dependent cocaine abusers maintained on buprenorphine vs methadone.	1999 Sep	12884887
Antidepressant drugs appear to enhance cocaine-induced toxicity.	2000 Feb	10743914
National Patterns of Medication Treatment for Depression, 1987 to 2001.	2001 Dec	15014590
Microheterogeneity of myocardial blood flow.	2001 Nov	11770072
[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
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
Validation of a simple, ethologically relevant paradigm for assessing anxiety in mice.	2003 Sep 1	12946884
Ethnic differences in substance abuse treatment retention, compliance, and outcome from two clinical trials.	2004 Feb	14762242
Discovering modes of action for therapeutic compounds using a genome-wide screen of yeast heterozygotes.	2004 Jan 9	14718172
Evaluation of fresh and cryopreserved hepatocytes as in vitro drug metabolism tools for the prediction of metabolic clearance.	2004 Nov	15286053
Inhibition of G protein-activated inwardly rectifying K+ channels by various antidepressant drugs.	2004 Oct	15150531
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
A selective test for antidepressant treatments using rats bred for stress-induced reduction of motor activity in the swim test.	2005 Oct	16047194
Enhanced neurally evoked responses and inhibition of norepinephrine reuptake in rat mesenteric arteries after spinal transection.	2006 Jan	16143650
[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
Frequency of high-risk use of QT-prolonging medications.	2006 Jun	16178046
Rhesus monkey trace amine-associated receptor 1 signaling: enhancement by monoamine transporters and attenuation by the D2 autoreceptor in vitro.	2007 Apr	17234900
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
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
The role of the entorhinal cortex in extinction: influences of aging.	2008	18584042
Do desipramine [10,11-dihydro-5-[3-(methylamino) propyl]-5H-dibenz[b,f]azepine monohydrochloride] and fluoxetine [N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]-propan-1-amine] ameliorate the extent of colonic damage induced by acetic acid in rats?	2008 Dec	18791062
The 5-hydroxytryptamine2A receptor antagonist R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl-4-piperidinemethanol (M100907) attenuates impulsivity after both drug-induced disruption (dizocilpine) and enhancement (antidepressant drugs) of differential-reinforcement-of-low-rate 72-s behavior in the rat.	2008 Dec	18772320
A novel approach for predicting antidepressant-induced sexual dysfunction in rats.	2008 Jan	17874315
D-161, a novel pyran-based triple monoamine transporter blocker: behavioral pharmacological evidence for antidepressant-like action.	2008 Jul 28	18561912
Community-based randomised controlled trial evaluating falls and osteoporosis risk management strategies.	2008 Nov 4	18983670
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

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 16 16:39:03 UTC 2022` Edited by `admin` on `Fri Dec 16 16:39:03 UTC 2022`
Record UNII	TG537D343B
Record Status	`Validated (UNII)`
Record Version

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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