Absorption, Distribution and Excretion
Desipramine hydrochloride is rapidly and almost completely absorbed from the gastrointestinal tract. It undergoes extensive first-pass metabolism. Peak plasma concentrations are attained 4 - 6 hours following oral administration.
Desipramine is metabolized in the liver, and approximately 70% is excreted in the urine.
...DESIPRAMINE /WAS GIVEN/ IN DOSE OF 25 MG EVERY 8 HR TO 15 PT. .../IT/ ACCUM IN BODY FOR PERIODS VARYING FROM 1 TO 16 DAYS, PEAK PLASMA LEVELS RANGING FROM 10 TO 275 UG/L...
IN ANIMALS, TRANSPLACENTAL PASSAGE HAS BEEN DEMONSTRATED RECENTLY OF...DESIPRAMINE...
AFTER IV ADMIN OF SINGLE DOSE OF DESMETHYLIMIPRAMINE...TO DOGS, RATE OF RENAL EXCRETION OF UNCHANGED DRUG DECR DRAMATICALLY IN INCREASING URINARY PH, WITH LITTLE CHANGE IN CREATININE CLEARANCE. ... URINARY EXCRETION...IN MAN WAS ALSO SHOWN TO BE PH-DEPENDENT...
THERE IS WIDE INTERPATIENT VARIATION IN STEADY-STATE PLASMA CONCN OF TRICYCLIC ANTIDEPRESSANTS. ...VARIATION SEEMS TO BE GENETICALLY DETERMINED... /TRICYCLIC ANTIDEPRESSANTS/
For more Absorption, Distribution and Excretion (Complete) data for DESIPRAMINE (6 total), please visit the HSDB record page.

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Metabolism / Metabolites
Desipramine is extensively metabolized in the liver by CYP2D6 (major) and CYP1A2 (minor) to 2-hydroxydesipramine, an active metabolite. 2-hydroxydesipramine is thought to retain some amine reuptake inhibition and may possess cardiac depressant activity. The 2-hydroxylation metabolic pathway of desipramine is under genetic control.
DEMETHYLIMIPRAMINE YIELDS BISDEMETHYLIMIPRAMINE, DEMETHYL-2-HYDROXYIMIPRAMINE, DEMETHYL-10-HYDROXYIMIPRAMINE, & IMINODIBENZYL IN MAN. /FROM TABLE/
DEMETHYLIMIPRAMINE YIELDS IMIPRAMINE IN RABBITS AND IN RATS. /FROM TABLE/
Desipramine has known human metabolites that include 2-hydroxy-desipramine and Desipramine N-glucuronide.
Desipramine is a known human metabolite of imipramine.
Desipramine is extensively metabolized in the liver by CYP2D6 (major) and CYP1A2 (minor) to 2-hydroxydesipramine, an active metabolite. 2-hydroxydesipramine is thought to retain some amine reuptake inhibition and may possess cardiac depressant activity. The 2-hydroxylation metabolic pathway of desipramine is under genetic control.
Route of Elimination: Desipramine is metabolized in the liver, and approximately 70% is excreted in the urine.
Half Life: 7-60+ hours; 70% eliminated renally

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Biological Half-Life
7-60+ hours; 70% eliminated renally
...DESIPRAMINE /WAS GIVEN/ IN DOSE OF 25 MG EVERY 8 HR TO 15 PT. ...BIOLOGICAL HALF-LIFE...FROM A FEW HR TO MORE THAN 2 DAYS...

Toxicity Summary
Desipramine is a tricyclic antidepressant (TCA) that selectively blocks reuptake of norepinephrine (noradrenaline) from the neuronal synapse. It also inhibits serotonin reuptake, but to a lesser extent compared to tertiary amine TCAs such as imipramine. Inhibition of neurotransmitter reuptake increases stimulation of the post-synaptic neuron. Chronic use of desipramine also leads to down-regulation of beta-adrenergic receptors in the cerebral cortex and sensitization of serotonergic receptors. An overall increase in serotonergic transmission likely confers desipramine its antidepressant effects. Desipramine also possesses minor anticholinergic activity, through its affinity for muscarinic receptors. TCAs are believed to act by restoring normal levels of neurotransmitters via synaptic reuptake inhibition and by increasing serotonergic neurotransmission via serotonergic receptor sensitization in the central nervous system.

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Toxicity Data
LD50: 290 mg/kg (Mouse) (A308)
LD50: 320 mg/kg (Rat) (A308)

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Interactions
ADMIN OF TRICYCLIC ANTIDEPRESSANTS...WITH OR SHORTLY AFTER...MAO INHIBITORS HAS RESULTED IN SEVERE REACTIONS. ... OTHER INTERACTIONS INCL POTENTIATION OF CENTRAL DEPRESSANT DRUGS, BLOCKADE OF ANTIHYPERTENSIVE EFFECTS OF GUANETHIDINE, & AUGMENTATION OF PRESSOR EFFECTS OF SYMPATHOMIMETIC AMINES. /TRICYCLIC ANTIDEPRESSANTS/
Concurrent use /of thyroid hormones/ with tricyclic antidepressants may increase the therapeutic and toxic effects of both medications, possibly due to increased receptor sensitivity to catecholamines; toxic effects include cardiac arrhythmias and CNS stimulation. /Tricyclic antidepressants/
Concurrent use /of sympathomimetics/ with tricyclic antidepressants may potentiate cardiovascular effects possibly resulting in arrhythmias, tachycardia, or severe hypertension or hyperpyrexia; phentolamine can control the adverse reaction. Significant systemic absorption of ophthalmic epinephrine may also potentiate cardiovascular effects; also, local anesthetics with vasoconstrictors should be avoided or a minimal amount of the vasoconstrictor should be used with the local anesthetic. Concurrent use with tricyclic antidepressants may decrease the pressor effect of ephedrine and mephentermine. /Tricyclic antidepressants/
If significant systemic absorption occurs, concurrent use /of ophthalmic naphazoline, nasal or ophthalmic oxymetazoline, nasal or ophthalmic phenylephrine, or nasal xylometazoline/ with tricyclic antidepressants may potentiate pressor effects of these medications. /Tricyclic antidepressants/
For more Interactions (Complete) data for DESIPRAMINE (20 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Rat oral 375 mg/kg
LD50 Rat ip 48 mg/kg
LD50 Rat sc 183 mg/kg
LD50 Rat iv 29 mg/kg
For more Non-Human Toxicity Values (Complete) data for DESIPRAMINE (8 total), please visit the HSDB record page.

[1]. Autoreceptor-mediated inhibition of norepinephrine release in rat medial prefrontal cortex is maintained after chronic desipramine treatment. J Neurochem. 2004 Nov;91(3):683-93.

[2]. Desipramine improves upper airway collapsibility and reduces OSA severity in patients with minimal muscle compensation. Eur Respir J. 2016 Nov;48(5):1340-1350.

Therapeutic Uses
Adrenergic Uptake Inhibitors; Antidepressive Agents, Tricyclic
...USED IN MANAGEMENT OF DEPRESSIVE STATES. DESIPRAMINE IS REPORTED TO BE OF BENEFIT IN ENDOGENOUS DEPRESSIONS SUCH AS MANIC DEPRESSIVE REACTIONS, & REACTIVE DEPRESSIONS.
...IF...GIVEN OVER PERIOD OF TIME TO DEPRESSED PATIENTS, ELEVATION OF MOOD OCCURS. ... 2-3 WK...BEFORE THERAPEUTIC EFFECTS...EVIDENT. /IMIPRAMINE/
ANTIDEPRESSANT
For more Therapeutic Uses (Complete) data for DESIPRAMINE (13 total), please visit the HSDB record page.

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Drug Warnings
SINCE TRICYCLIC ANTIDEPRESSANTS CAN CAUSE ORTHOSTATIC HYPOTENSION, PRODUCE ARRHYTHMIAS, & INTERACT IN DELETERIOUS WAYS WITH OTHER DRUGS...GREAT CAUTION MUST BE OBSERVED IN THEIR USE IN PT WITH SIGNIFICANT CARDIAC DISEASE. /TRICYCLIC ANTIDEPRESSANTS/
SPECIAL PRECAUTIONS SHOULD BE TAKEN IN PT WITH BENIGN PROSTATIC HYPERTROPHY. /IMIPRAMINE/
DESIPRAMINE HYDROCHLORIDE IS CONTRAINDICATED IN PATIENTS ON MONOAMINE OXIDASE-INHIBITOR THERAPY. .../IT/ SHOULD NOT BE GIVEN TO PT WITH GLAUCOMA, URETHRAL OR URETERAL SPASM, OR THOSE WHO HAVE HAD MYOCARDIAL INFARCTION WITHIN 3 WK. IT IS ALSO CONTRAINDICATED IN PT WITH SEVERE CORONARY HEART DISEASES OR WITH ACTIVE EPILEPSY. /HYDROGEN CHLORIDE/
The most common adverse effects of tricyclic antidepressants are those which result from anticholinergic activity. These include dry mucous membranes (occasionally associated with sublingual adenitis), blurred vision resulting from mydriasis and cycloplegia, increased intraocular pressure, hyperthermia, constipation, adynamic ileus, urinary retention, delayed micturition, and dilation of the urinary tract. The drugs have been reported to reduce the tone of the esophagogastric sphincter and to induce hiatal hernia in susceptible individuals or to exacerbate the condition in patients with preexisting hiatal hernias. Tricyclic antidepressants should be withdrawn if symptoms of esophageal reflux develop; if antidepressant therapy is essential, a cautious trial of a cholinergic agent such as bethanechol used concomitantly with the antidepressant may be warranted. Anticholinergic effects appear to occur most frequently in geriatric patients, but constipation is frequent in children receiving tricyclic antidepressants for functional enuresis. /Tricyclic antidepressants/
For more Drug Warnings (Complete) data for DESIPRAMINE (24 total), please visit the HSDB record page.

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Pharmacodynamics
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.

C18H22N2

266.38068

266.178

50-47-5

Desipramine hydrochloride;58-28-6;Desipramine-d3;65100-49-4;Desipramine-d4;61361-34-0

2995

Typically exists as solid at room temperature

1.047 g/cm3

407.4ºC at 760 mmHg

212°C

160.5ºC

1.5200 (estimate)

3.988

1

2

4

20

267

0

CNCCCN1C2=CC=CC=C2CCC3=CC=CC=C31

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

3-(5,6-dihydrobenzo[b][1]benzazepin-11-yl)-N-methylpropan-1-amine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)