Tìm theo
Desipramine
Các tên gọi khác (13 ) :
  • 3-(10,11-DIHYDRO-5H-dibenzo[b,F]azepin-5-yl)-N-methylpropan-1-amine
  • 5-(gamma-Methylaminopropyl)iminodibenzyl
  • 5-(γ-methylaminopropyl)iminodibenzyl
  • Déméthylimipramine
  • Desipramin
  • Desipramina
  • Desipramine
  • Desipraminum
  • Desmethylimipramine
  • DMI
  • Monodemethylimipramine
  • N-(3-methylaminopropyl)iminobibenzyl
  • Norimipramine
enzyme inhibitors, adrenergic uptake inhibitors, antidepressive agents tricyclic, antidepressive agents
Thuốc Gốc
Small Molecule
CAS: 50-47-5
ATC: N06AA01
ĐG : Actavis Group , http://www.actavis.com
CTHH: C18H22N2
PTK: 266.3807
Desipramine hydrochloride is a dibenzazepine-derivative tricyclic antidepressant (TCA). TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, desipramine does not affect mood or arousal, but may cause sedation. In depressed individuals, desipramine exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Secondary amine TCAs, such as desipramine and nortriptyline, are more potent inhibitors of norepinephrine reuptake than tertiary amine TCAs, such as amitriptyline and doxepine. TCAs also down-regulate cerebral cortical β-adrenergic receptors and sensitize post-synaptic serotonergic receptors with chronic use. The antidepressant effects of TCAs are thought to be due to an overall increase in serotonergic neurotransmission. TCAs also block histamine-H1 receptors, α1-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively. See toxicity section below for a complete listing of side effects. Desipramine exerts less anticholinergic and sedative side effects compared to tertiary amine TCAs, such as amitriptyline and clomipramine. Desipramine may be used to treat depression, neuropathic pain (unlabeled use), agitation and insomnia (unlabeled use) and attention-deficit hyperactivity disorder (unlabeled use).
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C18H22N2
Phân tử khối
266.3807
Monoisotopic mass
266.178298714
InChI
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
InChI Key
InChIKey=HCYAFALTSJYZDH-UHFFFAOYSA-N
IUPAC Name
(3-{2-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-yl}propyl)(methyl)amine
Traditional IUPAC Name
desipramine
SMILES
CNCCCN1C2=CC=CC=C2CCC2=CC=CC=C12
Độ tan chảy
214-218 °C
Độ hòa tan
58.6 mg/L (at 24 °C)
logP
4.90
logS
-3.66
pKa (Strongest Basic)
10.02
PSA
15.27 Å2
Refractivity
85.31 m3·mol-1
Polarizability
31.74 Å3
Rotatable Bond Count
4
H Bond Acceptor Count
2
H Bond Donor Count
1
Physiological Charge
1
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
caco2 Permeability
-4.67
pKa
10.4
Dược Lực Học : 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.
Cơ Chế Tác Dụng : Desipramine hydrochloride is a dibenzazepine-derivative tricyclic antidepressant (TCA). TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, desipramine does not affect mood or arousal, but may cause sedation. In depressed individuals, desipramine exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Secondary amine TCAs, such as desipramine and nortriptyline, are more potent inhibitors of norepinephrine reuptake than tertiary amine TCAs, such as amitriptyline and doxepine. TCAs also down-regulate cerebral cortical β-adrenergic receptors and sensitize post-synaptic serotonergic receptors with chronic use. The antidepressant effects of TCAs are thought to be due to an overall increase in serotonergic neurotransmission. TCAs also block histamine-H1 receptors, α1-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively. See toxicity section below for a complete listing of side effects. Desipramine exerts less anticholinergic and sedative side effects compared to tertiary amine TCAs, such as amitriptyline and clomipramine. Desipramine may be used to treat depression, neuropathic pain (unlabeled use), agitation and insomnia (unlabeled use) and attention-deficit hyperactivity disorder (unlabeled use). 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.
Dược Động Học :
▧ Absorption :
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.
▧ Protein binding :
73-92% bound to plasma proteins
▧ Metabolism :
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
Độc Tính : 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.
Chỉ Định : 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.
Tương Tác Thuốc :
  • Altretamine Risk of severe hypotension
  • Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
  • Atazanavir Atazanavir may increase the effect and toxicity of the tricyclic antidepressant, desipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of desipramine if atazanavir is initiated, discontinued or dose changed.
  • Avanafil Co-administration with avanafil resulted in an approximate 5.7% increase in AUC0-inf and 5.2% decrease in Cmax of rosiglitazone.
  • Butabarbital Barbiturates like butabarbital may increase the metabolism of tricyclic antidepressants like desipramine. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
  • Butalbital Barbiturates such as butalbital may increase the metabolism of tricyclic antidepressants such as desipramine. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
  • Carbamazepine Carbamazepine may decrease the serum concentration of the tricyclic antidepressant, desipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of desipramine if carbamazepine is initiated, discontinued or dose changed.
  • Cimetidine Cimetidine may increase the effect of the tricyclic antidepressant, desipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of desipramine if cimetidine is initiated, discontinued or dose changed.
  • Cisapride Increased risk of cardiotoxicity and arrhythmias
  • Clonidine The tricyclic antidepressant, desipramine, decreases the effect of clonidine.
  • Desvenlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Dihydroquinidine barbiturate Dihydroquinidine barbiturate increases the effect of the tricyclic antidepressant, desipramine.
  • Dobutamine The tricyclic antidepressant, desipramine, increases the sympathomimetic effect of dobutamine.
  • Donepezil Possible antagonism of action
  • Dopamine The tricyclic antidepressant, desipramine, increases the sympathomimetic effect of dopamine.
  • Duloxetine Possible increase in the levels of this agent when used with duloxetine
  • Ephedra The tricyclic antidepressant, desipramine, increases the sympathomimetic effect of ephedra.
  • Ephedrine The tricyclic antidepressant, desipramine, increases the sympathomimetic effect of ephedrine.
  • Epinephrine Trimipramine may increase the vasopressor effect of the direct-acting alpha-/beta-agonist, Epinephrine. Avoid combination if possible. Monitor sympathetic response to therapy if used concomitantly.
  • Fenoterol The tricyclic antidepressant, desipramine, increases the sympathomimetic effect of fenoterol.
  • Fluoxetine The SSRI, fluoxetine, may increase the serum concentration of the tricyclic antidepressant, desipramine, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of desipramine if fluoxetine is initiated, discontinued or dose changed.
  • Fluvoxamine The SSRI, fluvoxamine, may increase the serum concentration of the tricyclic antidepressant, desipramine, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of desipramine if fluvoxamine is initiated, discontinued or dose changed.
  • Galantamine Possible antagonism of action
  • Grepafloxacin Increased risk of cardiotoxicity and arrhythmias
  • Guanethidine The tricyclic antidepressant, desipramine, decreases the effect of guanethidine.
  • Indacaterol Concomitant therapy with monoamine oxidase inhibitors, tricyclic antidepressants, or other drugs that prolong the QTc interval should be monitored closely. These drugs may potentiate the effect of adrenergic agonist on the cardiovascular system.
  • Isocarboxazid Possibility of severe adverse effects
  • Isoprenaline The tricyclic antidepressant, desipramine, increases the sympathomimetic effect of isoproterenol.
  • Mephentermine The tricyclic antidepressant, desipramine, increases the sympathomimetic effect of mephentermine.
  • Metaraminol The tricyclic antidepressant, desipramine, increases the sympathomimetic effect of metaraminol.
  • Methoxamine The tricyclic antidepressant, desipramine, increases the sympathomimetic effect of methoxamine.
  • Mirabegron Mirabegron is a moderate CYP2D6 inhibitor and may cause an increase in exposure of CYP2D6 substrates. Monitor concomitant therapy closely.
  • Moclobemide Possible severe adverse reaction with this combination
  • Norepinephrine The tricyclic antidepressant, desipramine, increases the sympathomimetic effect of norepinephrine.
  • Orciprenaline The tricyclic antidepressant, desipramine, increases the sympathomimetic effect of orciprenaline.
  • Phenelzine Possibility of severe adverse effects
  • Phenylephrine The tricyclic antidepressant, desipramine, increases the sympathomimetic effect of phenylephrine.
  • Phenylpropanolamine The tricyclic antidepressant, desipramine, increases the sympathomimetic effect of phenylpropanolamine.
  • Pirbuterol The tricyclic antidepressant, desipramine, increases the sympathomimetic effect of pirbuterol.
  • Procaterol The tricyclic antidepressant, desipramine, increases the sympathomimetic effect of procaterol.
  • Pseudoephedrine The tricyclic antidepressant, desipramine, increases the sympathomimetic effect of pseudoephedrine.
  • Quinidine Additive QTc-prolonging effects may occur. Quinidine may also increase the serum concentration of the tricyclic antidepressant, desipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of desipramine if quinidine is initiated, discontinued or dose changed. Monitor for the development of torsades de pointes during concomitant therapy.
  • Quinidine barbiturate Quinidine barbiturate increases the effect of tricyclic antidepressant, desipramine.
  • Rasagiline Possibility of severe adverse effects
  • Rifabutin The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, desipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of desipramine if rifabutin is initiated, discontinued or dose changed.
  • Rifampicin The rifamycin, rifampin, may decrease the effect of the tricyclic antidepressant, desipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of desipramine if rifampin is initiated, discontinued or dose changed.
  • Ritonavir Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, desipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of desipramine if ritonavir if initiated, discontinued or dose changed.
  • Rivastigmine Possible antagonism of action
  • Salbutamol The tricyclic antidepressant, desipramine, increases the sympathomimetic effect of salbutamol.
  • Sibutramine Increased risk of CNS adverse effects
  • Sparfloxacin Increased risk of cardiotoxicity and arrhythmias
  • Tacrine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Desipramine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
  • Tacrolimus Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Tamoxifen Desipramine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
  • Tamsulosin Desipramine, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Desipramine is initiated, discontinued, or dose changed.
  • Terbinafine Terbinafine may increase the effect and toxicity of the tricyclic antidepressant, desipramine, by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of desipramine if terbinafine is initiated, discontinued or dose changed.
  • Terbutaline The tricyclic antidepressant, desipramine, increases the sympathomimetic effect of terbutaline.
  • Terfenadine Increased risk of cardiotoxicity and arrhythmias
  • Thiothixene May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
  • Tipranavir Tipranavir, co-administered with Ritonavir, may increase the concentration of Desipramine. Monitor Desipramine concentration and efficacy/toxicity and adjust dose as required.
  • Tolterodine Desipramine may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
  • Toremifene Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
  • Tramadol Tramadol increases the risk of serotonin syndrome and seizures. Desipramine may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Desipramine may decrease the effect of Tramadol by decreasing active metabolite production.
  • Tranylcypromine Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.
  • Trazodone Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Trimipramine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Triprolidine Triprolidine and Desipramine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
  • Trospium Trospium and Desipramine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
  • Venlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Vilazodone Monitor for toxic effects of tricyclic antidepressants if a selective serotonin reuptake inhibitor (SSRI) is initiated or the dose is increased. The influence of the SSRI may take several days or weeks to be fully realized or resolved.
  • Voriconazole Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
  • Vorinostat Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
  • Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
  • Zolmitriptan Use of two serotonin modulators, such as zolmitriptan and desipramine, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
  • Zuclopenthixol Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Liều Lượng & Cách Dùng : Tablet - Oral - 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty : Sanofi-Aventis
    Sản phẩm biệt dược : Norpramin
  • Công ty : Ciba
    Sản phẩm biệt dược : Pertofran
  • Công ty : USV
    Sản phẩm biệt dược : Pertofrane
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01151
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=2995
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46504624
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C06943
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D07791
ChemSpider
http://www.chemspider.com/Chemical-Structure.2888.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=35229
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0781-1971-01
PharmGKB
http://www.pharmgkb.org/drug/PA449233
Wikipedia
http://en.wikipedia.org/wiki/Desipramine
RxList
http://www.rxlist.com/cgi/generic2/desipram.htm
Drugs.com
http://www.drugs.com/cdi/desipramine.html
... loading
... loading