Desipramine

266.38

266.38

200-040-0

TG537D343B

DTXSID6022896

C61700

N - Nervous system

2933990090

15.3

3.7

white powder

1.047 g/cm3

25.0 °C

172-174 °C @ Press: 0.02 Torr

160.5ºC

1.5200 (estimate)

3.96e-02 g/L

Desipramine hydrochloride capsules and tablets should be stored in tight containers at a temperature less than 40 deg C, preferably at 15-30 deg C. /Desipramine hydrochloride/

10.4None

10.4

163.3 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]

3

20/21/22

36

Xn

UNSTABLE AFTER LONG EXPOSURE TO LIGHT, HEAT, & AIR /HYDROGEN CHLORIDE/

P260, P261, P264, P270, P271, P273, P301+P312, P304+P340, P307+P311, P312, P321, P330, P391, P403+P233, P405, P501

H302

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

|Danger|H302 (66.67%): Harmful if swallowed [Warning Acute toxicity, oral]|P260, P261, P264, P270, P271, P273, P301+P312, P304+P340, P307+P311, P312, P321, P330, P391, P403+P233, P405, and P501|Aggregated GHS information provided by 3 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Male mice: LD50 = 290 mg/kg, female rats: LD50 = 320 mg/kg. Antagonism of the histamine H1 and α1 receptors can lead to sedation and hypotension. Antimuscarinic activity confers anticholinergic side effects such as blurred vision, dry mouth, constipation and urine retention may occur. Cardiotoxicity may occur with high doses of desipramine. Cardiovascular side effects in postural hypotension, tachycardia, hypertension, ECG changes and congestive heart failure. Psychotoxic effects include impaired memory and delirium. Induction of hypomanic or manic episodes may occur in patients with a history of bipolar disorder. Withdrawal symptoms include GI disturbances (e.g. nausea, vomiting, abdominal pain, diarrhea), anxiety, insomnia, nervousness, headache and malaise.

Liver test abnormalities have been reported to occur in up to 16% of patients being treated with tricyclic antidepressants, but elevations are uncommonly above 3 times the upper limit of normal. The aminotransferase abnormalities are usually mild, asymptomatic and transient, reversing even with continuation of medication and without dose adjustment. Rare instances of clinically apparent acute liver injury have been reported due to desipramine, but far fewer than have been reported with amitriptyline or imipramine. The onset of jaundice is usually within 1 to 8 weeks of starting the antidepressant, and the pattern of serum enzyme elevations can be either hepatocellular or cholestatic. Features suggestive of hypersensitivity (fever, rash, eosinophilia) are common, but rarely severe. Autoantibody formation is unusual. These features are typical of tricyclic antidepressant hepatotoxicity.

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.

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.

73-92% bound to plasma proteins

For relief of symptoms in various depressive syndromes, especially endogenous depression. It has also been used to manage chronic peripheral neuropathic pain, as a second line agent for the management of anxiety disorders (e.g. panic disorder, generalized anxiety disorder), and as a second or third line agent in the ADHD management.|FDA Label

Desipramine is an oral tricyclic antidepressant that widely used in the therapy of depression. Desipramine can cause mild and transient serum enzyme elevations and is rare cause of clinically apparent acute cholestatic liver injury.

Antidepressants

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.

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.

TOLERANCE TO ANTICHOLINERGIC EFFECTS, SUCH AS DRY MOUTH, CONSTIPATION, BLURRED VISION, & TACHYCARDIA, TENDS TO DEVELOP WITH CONTINUED USE OF IMIPRAMINE. /IMIPRAMINE/

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.

Substances that contain a fused three-ring moiety and are used in the treatment of depression. These drugs block the uptake of norepinephrine and serotonin into axon terminals and may block some subtypes of serotonin, adrenergic, and histamine receptors. However the mechanism of their antidepressant effects is not clear because the therapeutic effects usually take weeks to develop and may reflect compensatory changes in the central nervous system. (See all compounds classified as Antidepressive Agents, Tricyclic.)|Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. (See all compounds classified as Enzyme Inhibitors.)|Drugs that block the transport of adrenergic transmitters into axon terminals or into storage vesicles within terminals. The tricyclic antidepressants (ANTIDEPRESSIVE AGENTS, TRICYCLIC) and amphetamines are among the therapeutically important drugs that may act via inhibition of adrenergic transport. Many of these drugs also block transport of serotonin. (See all compounds classified as Adrenergic Uptake Inhibitors.)

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.

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.

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...

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.|MANNER IN WHICH IMIPRAMINE RELIEVES...DEPRESSION...IS NOT CLEAR. .../EFFECT/ DESCRIBED AS DULLING OF DEPRESSIVE IDEATION RATHER THAN AS EUPHORIC STIMULATION PRODUCED BY MAO INHIBITORS...DEFINITIVELY DISCRIMINATIVE EXPT... YET TO BE PERFORMED. ...DOES HAVE STIMULANT ACTION UNDER CERTAIN CIRCUMSTANCES. /IMIPRAMINE/|ACTION OF TRICYCLIC ANTIDEPRESSANTS ON METABOLISM OF CATECHOLAMINES & INDOLEAMINES IN BRAIN HAS CONTRIBUTED SIGNIFICANTLY TO "BIOGENIC AMINE HYPOTHESIS" OF DEPRESSION. ... ALL TRICYCLIC ANTIDEPRESSANTS BLOCK RE-UPTAKE OF NOREPINEPHRINE BY ADRENERGIC NERVE TERMINALS. /TRICYCLIC ANTIDEPRESSANTS/|IMIPRAMINE SLOWS TURNOVER RATE OF 5-HT, EFFECT NOT SHARED BY DESIPRAMINE, WHILE TURNOVER RATE OF NOREPINEPHRINE IS INCR BY DEMETHYLATED DRUGS NORTRIPTYLINE & DESIPRAMINE. EXACT RELATIONSHIP OF THESE EFFECTS TO ACTIONS OF TRICYCLIC ANTIDEPRESSANTS IN HUMAN DEPRESSION IS NOT KNOWN.

MILD PARKINSONIAN SYNDROME...MAY BE SEEN IN SOME PT, PARTICULARLY OLDER PERSONS TAKING LARGE DOSES. ...HIGH DOSES...MAY PRODUCE GRAND MAL SEIZURES EVEN IN PT WITHOUT HISTORY OF CONVULSIONS. .../IT/ MAY PRODUCE ALLERGIC TYPE OF OBSTRUCTIVE JAUNDICE.../WHICH/ CLEARS WHEN DRUG IS DISCONTINUED. /IMIPRAMINE/|Effects of overdosage include agitation, hallucinations, hyperreflexia, hyperpyrexia, and convulsions. Both hypotension and hypertension also occur.

Apo Desipramine

DESIPRAMINE HYDROCHLORIDE, NF: NORPRAMIN, CAPSULES: 25, 50 MG; PERTOFRANE, TABLETS: 25, 50 MG /HYDROGEN CHLORIDE, FROM TABLE/

PREPN OF HYDROCHLORIDE: BELGIAN PATENT 614,616, CA 58 11338C (1963), (1962 TO GEIGY)

DETERMINATION OF IMIPRAMINE & DESIPRAMINE IN BLOOD BY FLUORIMETRY @ EXCITATION WAVELENGTH OF 290 NM & EMISSION WAVELENGTH OF 415 NM; CURRY, A, POISON DETECTION IN HUMAN ORGANS, 2ND ED, CHARLES C THOMAS, SPRINGFIELD, 1969, 135.|COLORIMETRIC DETERMINATION OF IMIPRAMINIC DRUGS IN BLOOD & URINE.|DETERMINATION OF TRICYCLIC ANTIDEPRESSANTS & SOME OF THEIR METABOLITES IN SERUM BY STRAIGHT PHASE HPLC.|DETERMINATION OF DRUGS IN PLASMA BY HIGH-PERFORMANCE TLC & QUANTITATIVE ANALYSIS OF SEPARATED COMPONENTS BY UV REFLECTANCE SPECTROMETRY.|For more Clinical Laboratory Methods (Complete) data for DESIPRAMINE (6 total), please visit the HSDB record page.

Pharmaceuticals