Rats administered desipramine hydrochloride for a duration of 14 days exhibited a dose-dependent decrease in the expression of norepinephrine transporter (NET). This was demonstrated by a decrease in the specific binding of 3H-nisoxetine to NET in cerebral cortex preparations (F(3,16) =4.33, p<0.05), as well as in the hippocampus (F(3,16) =4.34, p<0.05). When plasma and brain concentrations of desipramine hydrochloride and desmethyldesipramine hydrochloride were undetectable (that is, below the assay's 25 ng detection limit), this NET downregulation was discovered two days after long-term desipramine hydrochloride treatment was stopped[2].

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 reached 4–6 hours after oral administration. Desipramine is metabolized in the liver, with approximately 70% excreted in the urine. …Desipramine/administer/25 mg every 8 hours, up to 15 PT. .../IT/ The accumulation time in the body varies from 1 to 16 days, with peak plasma concentrations ranging from 10 to 275 μg/L... Desipramine has recently been shown to be transplacental in animals... Following a single intravenous injection of normethoprim in dogs, renal excretion of unmetabolized drugs decreased significantly with increasing urinary pH, while creatinine clearance remained almost unchanged. ...Urinary excretion... has also been shown to be pH-dependent in humans... There is significant inter-patient variability in steady-state plasma concentrations of tricyclic antidepressants. ...This difference appears to be determined by genetic factors... /Tricyclic Antidepressants/
For more complete data on the absorption, distribution, and excretion of desipramine (6 types), please visit the HSDB record page.

---

Metabolism/Metabolites
Desipramine is primarily metabolized in the liver via CYP2D6 and secondarily via CYP1A2, producing the active metabolite 2-hydroxydesipramine. 2-Hydroxydesipramine is thought to retain some amine reuptake inhibitory activity and may have cardiodepressant activity. The 2-hydroxylation metabolic pathway of desipramine is genetically controlled.
In humans, normethylimipramine can be converted to bis(normethylimipramine), nor-2-hydroxyimipramine, nor-10-hydroxyimipramine, and iminodibenzylimipramine. (From table)
In rabbits and mice, normethylimipramine can be converted to imipramine. /Excerpt from table/
The known metabolites of desipramine include 2-hydroxydesipramine and desipramine N-glucuronide.
Desipramine is a known metabolite of imipramine.
Desipramine is metabolized in the liver primarily by CYP2D6 (major) and CYP1A2 (minor) to the active metabolite 2-hydroxydesipramine. 2-hydroxydesipramine is thought to retain some amine reuptake inhibitory activity and may have cardiodepressant activity. The 2-hydroxylation metabolic pathway of desipramine is genetically controlled.
Elimination pathway: Desipramine is metabolized in the liver, with approximately 70% excreted in the urine.
Half-life: 7-60+ hours; 70% excreted by the kidneys.
…Desipramine/Administered/25 mg every 8 hours, treated 15 patients. ...biological half-life...from a few hours to more than 2 days...

Toxicity Summary
Desipramine is a tricyclic antidepressant (TCA) that selectively blocks the reuptake of norepinephrine from neuronal synapses. It also inhibits serotonin reuptake, but to a lesser extent than tertiary amine TCAs such as imipramine. Inhibition of neurotransmitter reuptake enhances the excitability of postsynaptic neurons. Long-term use of desipramine can also lead to downregulation of β-adrenergic receptors and sensitization of serotonergic receptors in the cerebral cortex. This overall enhancement of serotonergic transmission may be the reason for desipramine's antidepressant effect. Desipramine also has mild anticholinergic activity due to its affinity for muscarinic receptors. Tricyclic antidepressants (TCAs) are thought to restore normal neurotransmitter levels by inhibiting synaptic reuptake and to increase serotonergic neurotransmission through sensitization of serotonergic receptors in the central nervous system.

---

Toxicity Data
LD50: 290 mg/kg (mice) (A308)
LD50: 320 mg/kg (rat) (A308)

---

Interactions
Concomitant use of tricyclic antidepressants with monoamine oxidase inhibitors (MAOIs) or shortly after MAOI administration can lead to serious reactions. Other interactions include enhancing the effects of central nervous system depressants, blocking the hypotensive effect of guanethidine, and enhancing the hypertensive effect of sympathomimetic amines. /Tricyclic Antidepressants/
Concomitant use of thyroid hormones with tricyclic antidepressants may enhance the therapeutic and toxic effects of both drugs, possibly due to increased receptor sensitivity to catecholamines; toxic effects include arrhythmias and central nervous system excitation. /Tricyclic Antidepressants/
Concomitant use of sympathomimetic amines with tricyclic antidepressants may enhance cardiovascular effects, potentially leading to arrhythmias, tachycardia, or severe hypertension or hyperthermia; phentolamine can control these adverse reactions. Significant systemic absorption of ophthalmic epinephrine may also enhance its cardiovascular effects; furthermore, local anesthetics containing vasoconstrictors should be avoided, or only very small amounts of vasoconstrictors should be used in local anesthetics. Concomitant use with tricyclic antidepressants may reduce the pressor effects of ephedrine and mephentermine. /Tricyclic Antidepressants/
If significant systemic absorption occurs, concomitant use with tricyclic antidepressants/ophthalmic naphazoline, nasal or ophthalmic oxymetazoline, nasal or ophthalmic epinephrine, or nasal xylometazoline/ may enhance the pressor effects of these drugs. /Tricyclic Antidepressants/
For more complete interaction data (of 20 items) on desipramine, please visit the HSDB record page.

---

Non-human toxicity values
Oral LD50 in rats: 375 mg/kg
Intraperitoneal LD50 in rats: 48 mg/kg
Subcutaneous LD50 in rats: 183 mg/kg
Intravenous LD50 in rats: 29 mg/kg
For more complete (8 data points) non-human toxicity values for desipramine, please visit the HSDB record page.

[1]. Plasma membrane monoamine transporters: structure, regulation and function. Nat Rev Neurosci. 2003 Jan;4(1):13-25.

[2]. Norepinephrine transporter regulation mediates the long-term behavioral effects of the antidepressant desipramine. Neuropsychopharmacology. 2008 Dec;33(13):3190-200.

Therapeutic Uses

Adrenergic reuptake inhibitors; tricyclic antidepressants.
...Used to treat depression. Desipramine has been reported to be beneficial for endogenous depression (such as bipolar disorder and reactive depression).
...If...given to patients with depression over a period of time, mood will improve. ...Therapeutic effects can be observed after 2-3 weeks. /Imipramine/
Antidepressants
For more complete data on the therapeutic uses of desipramine (13 in total), please visit the HSDB record page.

---

Drug Warnings
Because tricyclic antidepressants can cause orthostatic hypotension, arrhythmias, and harmful interactions with other drugs...extra caution must be exercised when using them in patients with severe heart disease. /Tricyclic Antidepressants/
Special caution should be exercised in patients with benign prostatic hyperplasia. Desipramine hydrochloride is contraindicated in patients receiving monoamine oxidase inhibitor therapy.
...Patients with glaucoma, urethral or ureteral spasms, or who have had a myocardial infarction within the past 3 weeks are contraindicated. Patients with severe coronary artery disease or active epilepsy are also contraindicated. The most common adverse reactions of tricyclic antidepressants are caused by anticholinergic activity. These adverse reactions include dry mucosa (sometimes accompanied by sublingual gland inflammation), blurred vision due to mydriasis and cycloplegia, increased intraocular pressure, hyperthermia, constipation, amoxicillin obstruction, urinary retention, delayed urination, and urethral dilation. These drugs have been reported to reduce the tone of the esophageal and gastric sphincters and induce hiatal hernias in susceptible populations or worsen existing hiatal hernias. If symptoms of esophageal reflux occur, tricyclic antidepressants should be discontinued; if antidepressant treatment is necessary, cautious consideration may be given to the concurrent use of cholinergic drugs, such as betanyl. Anticholinergic effects appear to occur most frequently in elderly patients, but constipation is also common in children taking tricyclic antidepressants for functional enuresis. /Tricyclic Antidepressants/
For more complete data on drug warnings for desipramine (24 in total), please visit the HSDB records page.

---

Pharmacodynamics
Desipramine is a secondary amine tricyclic antidepressant whose structure is related to the skeletal muscle relaxant cyclobenzaline and the thioxanthracene antipsychotic (such as thiothoxanthracene). It is the active metabolite of imipramine (a tertiary amine tricyclic antidepressant). The acute effects of desipramine include inhibition of norepinephrine reuptake at noradrenergic nerve endings and inhibition of serotonin (5-hydroxytryptamine, 5-HT) reuptake at serotonergic nerve endings in the central nervous system. Desipramine has a stronger inhibitory effect on norepinephrine reuptake compared to the tertiary amine tricyclic antidepressant imipramine. In addition to inhibiting neurotransmitter reuptake, desipramine can downregulate β-adrenergic receptors in the cerebral cortex and sensitize serotonergic receptors with long-term use. Its overall effect is enhanced serotonergic neurotransmission. Antidepressant effects typically appear 2-4 weeks after treatment begins, but some patients may require up to 8 weeks of treatment to see symptom improvement. Patients experiencing major depressive episodes may respond more quickly than those with mild depressive symptoms.

C18H22N2.HCL

302.84162

302.154

58-28-6

Desipramine-d3;65100-49-4;Desipramine;50-47-5;Desipramine-d4;61361-34-0

2995

White to off-white solid powder

407.4ºC at 760 mmHg

214-216ºC

160.5ºC

4.79

1

2

4

20

267

0

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

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

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

DMSO : ≥ 100 mg/mL (~330.21 mM)
H2O : ~100 mg/mL (~330.21 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.26 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.5 mg/mL (8.26 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (8.26 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

Solubility in Formulation 4: 1 mg/mL (3.30 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C).

---

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