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Desipramin
DMI 50475 · Pentofran · Sertofran · Desipramin · Pertrofane · esipramine · DESIPRAMINE · Desimpramine
Identifikatoren & physikalische Daten
| CAS No. | 50-47-5 |
|---|---|
| Summenformel | C18H22N2 |
| Durchschnittliche Molmasse | 266,4 g/mol |
| Monoisotopische Masse | 266,1782987 g/mol |
| SMILES | CNCCCN1c2ccccc2CCc2ccccc21 |
| InChIKey | HCYAFALTSJYZDH-UHFFFAOYSA-N |
| PubChem CID | 2995 |
| ChEMBL | CHEMBL72 |
| ChEBI | CHEBI:47781 |
| EC No. | 200-040-0 |
| DTXSID | DTXSID6022896 |
| Lokaler Name | Desipramin |
Chemische & physikalische Eigenschaften
| XLogP | 4,9 |
|---|---|
| Polarare Oberfläche (TPSA) | 15,3 |
| H-Brücken-Donoren | 1 |
| H-Brücken-Akzeptoren | 2 |
| Frei drehbare Bindungen | 4 |
| Schwere Atome | 20 |
| Formalladung | 0 |
| Komplexität | 267 |
| Arzneimittel | DEA NFLIS-Drug Category -> AntidepressantsPharmaceuticalsPharmaceuticals -> Listed in ZINC15 |
| LogP (Verteilungskoeffizient) | log Kow = 4.903.74.0 |
| Löslichkeit | WHITE CRYSTALLINE POWDERODORLESSBITTER TASTEMELTS WITHIN 5 DEG RANGE BETWEEN 208-218 °C1 G IN CA 4 ML CHLOROFORM, 20 ML WATER, 20 ML ALCFREELY SOL IN METHANOLINSOL IN ETHER /HCL/In water, 58.6 mg/l @ 24 °C.3.96e-02 g/L |
| Human Drugs | Antidepressants -> Tricyclic antidepressants (TCA)Breast FeedingLactationMilk, HumanAntidepressive AgentsAntidepressive Agents, TricyclicPharmaceuticals |
| Siedepunkt | 172-174 °C @ 0.02 MM HGbp0.02 172-174° |
| Decomposition | When heated to decomposition it emits toxic fumes of nitroxides. |
| Schmelzpunkt | 214-218 °C214 - 218 °C212°C |
| Physical Description | Solid |
| Stability/Shelf Life | UNSTABLE AFTER LONG EXPOSURE TO LIGHT, HEAT, & AIR /HYDROGEN CHLORIDE/ |
| Dissociation Constants | 10.1610.2310.4 |
| Collision Cross Section | 163.5 Ų [M+H]+ [CCS Type: DTBuffer gas: N2Ionization: ESI+Dataset: Antidepressants]160.93 Ų [M+H]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]163.3 Ų [M+H]+ [CCS Type: TWMethod: Major Mix IMS/Tof Calibration Kit (Waters)] |
| Dichte | 0.9934 (rough estimate) |
| Brechungsindex | 1.5200 (estimate) |
| pKa (Säurekonstante) | pKa 10.21(-)(H2O t=20) (Uncertain) |
| Aggregatzustand | powder |
| Farbe | white |
| EPA chemische Informationen | Desipramine (50-47-5) |
Sicherheit & Vorschriften
| GHS-Einstufung | DangerH302 (66.7%): Harmful if swallowed [Warning Acute toxicity, oral]P260, P261, P264, P270, P271, P273, P301+P317, P304+P340, P308+P316, P319, P321, P330, P391, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 3 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| Regulatorische Informationen | Status: Active Update: 08-02-2018 https://echa.europa.eu/registration-dossier/-/registered-dossier/223535H-Dibenzb,fazepine-5-propanamine, 10,11-dihydro-N-methyl-: Does not have an individual approval but may be used under an appropriate group standard |
| Weitere Sicherheitsinformationen | IMAP assessments - 5H-Dibenz[b,f]azepine-5-propanamine, 10,11-dihydro-N-methyl-: Environment tier I assessment |
| FDA-Anforderungen | 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 amended21 U.S.C. 321-392). |
| Hazard Classes and Categories | Acute Tox. 4 (66.7%) |
| Lagerbedingungen | Desipramine hydrochloride capsules and tablets should be stored in tight containers at a temperature less than 40 °C, preferably at 15-30 °C. /Desipramine hydrochloride/ |
| Entsorgungsverfahren | 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. |
| Treatment | Obtain an ECG and immediately initiate cardiac monitoring. Protect the patient's airway, establish an intravenous line, and initiate gastric decontamination. A minimum of 6 hours of observation with cardiac monitoring and observation for signs of CNS or respiratory depression, hypotension, cardiac dysrhythmias and/or conduction blocks, and seizures is necessary. If signs of toxicity occur at any time during this period, extended monitoring is required. Follow ECG, renal function, CPK, and arterial blood gasses as clinically indicated. (L1712) |
| Wechselwirkungen | 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 catecholaminestoxic 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 hyperpyrexiaphentolamine can control the adverse reaction. Significant systemic absorption of ophthalmic epinephrine may also potentiate cardiovascular effectsalso, 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. |
| Hepatotoxicity | 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. |
| Unerwünschte Wirkungen | Desipramine has a broad toxic profile, including an increased risk of suicide, orthostatic hypotension, cardiac abnormalities, seizures, ocular crisis, and fractures. A short-term study demonstrated a significantly increased risk of suicide in children, adolescents, and young adults aged 24 and youngerthis represents one of the most significant adverse effects to consider when prescribing desipramine. Orthostatic hypotension, likely due to alpha-1 receptor blockade, is a common reason for drug discontinuation. Reports describe cardiovascular adverse effects, including heart block, arrhythmias, and sudden death associated with desipramine. Clinicians should screen for conduction abnormalities, with particular attention to the QT interval and family history of cardiac disease, before prescribing desipramine. |
| Expositionspfade | 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. |
| Toxizitätsübersicht | Signs and Symptoms of OverdoseDesipramine 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. |
| Human Toxicity Excerpts | 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. |
| Carcinogen Classification | No indication of carcinogenicity to humans (not listed by IARC). |
| Drug Induced Liver Injury | Benchmark Dataset for the Liver Toxicity Knowledge Base (LTKB)desipramineNorpramin®Antidepressants3less-DILI-concern drugs |
| Non-Human Toxicity Excerpts | IN CATS UNDER ANESTHESIA IV INJECTION OF 4 TO 25 MG OF DESIPRAMINE HAS BEEN FOUND TO REDUCE SPONTANEOUS ACTIVITY OF RETINAL NEURONES. DOSES OF 5 TO 20 MG/KG INCR C-WAVE IN ELECTRORETINOGRAM, & DOSES OF 20 TO 35 MG/KG REDUCED B-WAVE...DESPITE ITS CLINICAL ANTIDEPRESSANT EFFECTS, IMIPRAMINE PRODUCES DEPRESSION OF SPONTANEOUS MOTOR ACTIVITY IN LAB ANIMALS. ...IT ALSO...DECR BODY TEMP, & CAUSES ATAXIA. IT IMPAIRS BOTH ACQUISITION & PERFORMANCE OF CONDITIONED AVOIDANCE RESPONSES. /IMIPRAMINE/IMIPRAMINE LOWERS BLOOD PRESSURE IN ANESTHETIZED DOGS & OBTUNDS VARIOUS CARDIOVASCULAR REFLEXES, INCL CAROTID OCCLUSION REFLEX, BEZOLD-JARISCH REFLEX, & POSTURAL RESPONSES. /IMIPRAMINE/ |
| Effects During Pregnancy and Lactation | ◉ Summary of Use during Lactation◈ What is desipramine? |
| Toxicity Data | LD50: 290 mg/kg (Mouse) (A308) LD50: 320 mg/kg (Rat) (A308) |
| Wassergefährdungsklasse (WGK) | 3 |
| R-Sätze (R) | 20/21/22 |
| Gefahrensymbole | Xn |
| Sicherheitshinweise (S) | 36 |
| Gefahrstoffdaten | 50-47-5(Hazardous Substances Data) |
Anwendungen & Verwendung
Verwenden
Desipramine is used for depression of various etiology and in particular for endogenous depression.