Tìm theo
Imipramine
Các tên gọi khác (12 ) :
  • 10,11-dihydro-N,N-Dimethyl-5H-dibenz[b,F]azepine-5-propanamine
  • 3-(5H-DIBENZO[b,F]azepin-5-yl)-N,N-dimethylpropan-1-amine
  • 5-[3-(dimethylamino)Propyl]-10,11-dihydro-5H-dibenz[b,F]azepine
  • Antideprin
  • Imipramin
  • Imipramine
  • Imipraminum
  • Imizine
  • Irmin
  • Melipramine
  • N-(gamma-Dimethylaminopropyl)iminodibenzyl
  • N-(γ-dimethylaminopropyl)iminodibenzyl
adrenergic uptake inhibitors, antidepressive agents tricyclic
Thuốc Gốc
Small Molecule
CAS: 50-49-7
ATC: N06AA03, N06AA06, N06AA02
ĐG : Actavis Group , http://www.actavis.com
CTHH: C19H24N2
PTK: 280.4073
Imipramine, the prototypical tricyclic antidepressant (TCA), is a dibenzazepine-derivative 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, imipramine does not affect mood or arousal, but may cause sedation. In depressed individuals, imipramine exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Tertiary amine TCAs, such as imipramine and amitriptyline, are more potent inhibitors of serotonin reuptake than secondary amine TCAs, such as nortriptyline and desipramine. 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. Imipramine has less sedative and anticholinergic effects than the tertiary amine TCAs, amitriptyline and clomipramine. See toxicity section below for a complete listing of side effects. Imipramine may be used to treat depression and nocturnal enuresis in children. Unlabeled indications include chronic and neuropathic pain (including diabetic neuropathy), panic disorder, attention-deficit/hyperactivity disorder (ADHD), and post-traumatic stress disorder (PTSD).
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C19H24N2
Phân tử khối
280.4073
Monoisotopic mass
280.193948778
InChI
InChI=1S/C19H24N2/c1-20(2)14-7-15-21-18-10-5-3-8-16(18)12-13-17-9-4-6-11-19(17)21/h3-6,8-11H,7,12-15H2,1-2H3
InChI Key
InChIKey=BCGWQEUPMDMJNV-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)dimethylamine
Traditional IUPAC Name
imipramine
SMILES
CN(C)CCCN1C2=CC=CC=C2CCC2=CC=CC=C12
Độ tan chảy
174-175
Độ sôi
160 °C at 1.00E-01 mm Hg
Độ hòa tan
18.2 mg/L (at 24 °C)
logP
4.80
logS
-4.19
pKa (Strongest Basic)
9.2
PSA
6.48 Å2
Refractivity
90.61 m3·mol-1
Polarizability
33.39 Å3
Rotatable Bond Count
4
H Bond Acceptor Count
2
H Bond Donor Count
0
Physiological Charge
1
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
caco2 Permeability
-4.85
pKa
9.4
Dược Lực Học : Imipramine is a tricyclic antidepressant with general pharmacological properties similar to those of structurally related tricyclic antidepressant drugs such as amitriptyline and doxepin. A tertiary amine, imipramine inhibits the reuptake of serotonin more so than most secondary amine tricyclics, meaning that it blocks the reuptake of neurotransmitters serotonin and noradrenaline almost equally. With chronic use, imipramine also down-regulates cerebral cortical β-adrenergic receptors and sensitizes post-synaptic sertonergic receptors, which also contributes to increased serotonergic transmission. It takes approximately 2 - 4 weeks for antidepressants effects to occur. The onset of action may be longer, up to 8 weeks, in some individuals. It is also effective in migraine prophylaxis, but not in abortion of acute migraine attack.
Cơ Chế Tác Dụng : Imipramine, the prototypical tricyclic antidepressant (TCA), is a dibenzazepine-derivative 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, imipramine does not affect mood or arousal, but may cause sedation. In depressed individuals, imipramine exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Tertiary amine TCAs, such as imipramine and amitriptyline, are more potent inhibitors of serotonin reuptake than secondary amine TCAs, such as nortriptyline and desipramine. 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. Imipramine has less sedative and anticholinergic effects than the tertiary amine TCAs, amitriptyline and clomipramine. See toxicity section below for a complete listing of side effects. Imipramine may be used to treat depression and nocturnal enuresis in children. Unlabeled indications include chronic and neuropathic pain (including diabetic neuropathy), panic disorder, attention-deficit/hyperactivity disorder (ADHD), and post-traumatic stress disorder (PTSD). Imipramine works by inhibiting the neuronal reuptake of the neurotransmitters norepinephrine and serotonin. It binds the sodium-dependent serotonin transporter and sodium-dependent norepinephrine transporter preventing or reducing the reuptake of norepinephrine and serotonin by nerve cells. Depression has been linked to a lack of stimulation of the post-synaptic neuron by norepinephrine and serotonin. Slowing the reuptake of these neurotransmitters increases their concentration in the synaptic cleft, which is thought to contribute to relieving symptoms of depression. In addition to acutely inhibiting neurotransmitter re-uptake, imipramine causes down-regulation of cerebral cortical beta-adrenergic receptors and sensitization of post-synaptic serotonergic receptors with chronic use. This leads to enhanced serotonergic transmission.
Dược Động Học :
▧ Absorption :
Rapidly and well absorbed after oral administration. Bioavailability is approximately 43%. Peak plasma concentrations usually attained 1 - 2 hours following oral administration. Absorption is unaffected by food.
▧ Protein binding :
60-95%
▧ Metabolism :
Exclusively metabolized by the liver. Imipramine is converted in the liver by various CYP isoenzymes (e.g. CYP1A2, CYP2D6, CYP3A4, CYP2C9) to active metabolites desipramine and 2-hydroxydesipramine.
▧ Route of Elimination :
Approximately 40% of an orally administered dose is eliminated in urine within 24 hours, 70% in 72 hours. Small amounts are eliminated in feces via the biliary elimination.
▧ Half Life :
Imipramine - 8-20 hours; Desipramine (active metabolite) - up to 125 hours
Độc Tính : Oral, rat LD50: 355 to 682 mg/kg. Toxic signs proceed progressively from depression, irregular respiration and ataxia to convulsions and death. Antagonism of the histamine H1 and α1 receptors can lead to sedation and hypotension. Antimuscarinic and anticholinergic side effects such as blurred vision, dry mouth, constipation and urine retention may occur. Cardiotoxicity may occur with high doses of imipramine. 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 the relief of symptoms of depression and as temporary adjunctive therapy in reducing enuresis in children aged 6 years and older. May also be used to manage panic disorders, with or without agoraphobia, as a second line agent in ADHD, management of eating disorders, for short-term management of acute depressive episodes in bipolar disorder and schizophrenia, and for symptomatic treatment of postherpetic neuralgia.
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, imipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of imipramine if atazanavir if initiated, discontinued or dose changed.
  • Butabarbital Barbiturates like butabarbital may increase the metabolism of tricyclic antidepressants like imipramine. 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 imipramine. 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, imipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of imipramine if carbamazepine is initiated, discontinued or dose changed.
  • Cimetidine Cimetidine may increase the effect of the tricyclic antidepressant, imipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of imipramine if cimetidine is initiated, discontinued or dose changed.
  • Cisapride Increased risk of cardiotoxicity and arrhythmias
  • Clonidine The tricyclic antidepressant, imipramine, 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, imipramine.
  • Dobutamine The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of dobutamine.
  • Donepezil Possible antagonism of action
  • Dopamine The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of dopamine.
  • Duloxetine Possible increase in the levels of this agent when used with duloxetine
  • Ephedra The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of ephedra.
  • Ephedrine The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of ephedrine.
  • Epinephrine The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of epinephrine.
  • Fenoterol The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of fenoterol.
  • Fluconazole Fluconazole may increase the effect and toxicity of the tricyclic antidepressant, imipramine, by decreasing its metabolism. Additive QTc-prolonging effects may also occur. Monitor for changes in the therapeutic and adverse effects of imipramine if fluconazole is initiated, discontinued or dose changed. Monitor for the development of torsades de pointes during concomitant therapy.
  • Fluoxetine The SSRI, fluoxetine, may increase the serum concentration of the tricyclic antidepressant, imipramine, 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 imipramine if fluoxetine is initiated, discontinued or dose changed.
  • Fluvoxamine The SSRI, fluvoxamine, may increase the serum concentration of the tricyclic antidepressant, imipramine, 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 imipramine if fluvoxamine is initiated, discontinued or dose changed.
  • Galantamine Possible antagonism of action
  • Grepafloxacin Increased risk of cardiotoxicity and arrhythmias
  • Guanethidine The tricyclic antidepressant, imipramine, may increase the sympathomimetic effect of guanethidine.
  • Iobenguane May diminish the therapeutic effect and increase chances of producing a false negative imaging result of Iobenguane as it inhibits noradrenaline transporter function
  • Isocarboxazid Possibility of severe adverse effects
  • Isoprenaline The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of isoproterenol.
  • Ketoconazole Ketoconazole, a moderate CYP2D6 inhibitor, may increase the serum concentration of imipramine by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of imipramine if ketoconazole is initiated, discontinued or dose changed.
  • Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
  • Mephentermine The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of mephentermine.
  • Mesoridazine Increased risk of cardiotoxicity and arrhythmias
  • Metaraminol The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of metaraminol.
  • Methoxamine The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of methoxamine.
  • Moclobemide Possible severe adverse reaction with this combination
  • Norepinephrine The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of norepinephrine.
  • Orciprenaline The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of orciprenaline.
  • Phenelzine Possibility of severe adverse effects
  • Phenylephrine The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of phenylephrine.
  • Phenylpropanolamine The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of phenylpropanolamine.
  • Pirbuterol The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of pirbuterol.
  • Procaterol The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of procaterol.
  • Pseudoephedrine The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of pseudoephedrine.
  • Quinidine Additive QTc-prolonging effects may occur. Quinidine may also increase the serum concentration of the tricyclic antidepressant, imipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of imipramine 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, imipramine.
  • Rasagiline Possibility of severe adverse effects
  • Rifabutin The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, imipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of imipramine if rifabutin is initiated, discontinued or dose changed.
  • Rifampicin The rifamycin, rifampin, may decrease the effect of the tricyclic antidepressant, imipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of imipramine if rifampin is initiated, discontinued or dose changed.
  • Ritonavir Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, imipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of imipramine if ritonavir if initiated, discontinued or dose changed.
  • Rivastigmine Possible antagonism of action
  • Salbutamol The tricyclic antidepressant, imipramine, 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, Imipramine, 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 Imipramine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
  • Tamsulosin Imipramine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Imipramine is initiated, discontinued, or dose changed.
  • Terbinafine Terbinafine may increase the effect and toxicity of the tricyclic antidepressant, imipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of imipramine if terbinafine is initiated, discontinued or dose changed.
  • Terbutaline The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of terbutaline.
  • Terfenadine Increased risk of cardiotoxicity and arrhythmias
  • Thioridazine 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.
  • Ticlopidine Ticlopidine may decrease the metabolism and clearance of Imipramine. Consider alternate therapy or monitor for adverse/toxic effects of Imipramine if Ticlopidine is initiated, discontinued or dose changed.
  • 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. Imipramine 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.
  • Trimethobenzamide Trimethobenzamide and Imipramine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
  • Trimipramine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Triprolidine Triprolidine and Imipramine, 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 Imipramine, 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.
  • 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 imipramine, 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 : Capsule - Oral - 75 mg, 100 mg, 125 mg, 150 mg
Tablet - Oral - 10 mg, 25 mg, 50 mg
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty : Torrent
    Sản phẩm biệt dược : Antidep
  • Công ty : Abbott
    Sản phẩm biệt dược : Depsonil
  • Công ty : Abbott
    Sản phẩm biệt dược : Depsonil-PM
  • Công ty : Baroda
    Sản phẩm biệt dược : Elamin
  • Công ty : Johnson
    Sản phẩm biệt dược : Fronil
  • Sản phẩm biệt dược : Imidol
  • Công ty : Nycomed
    Sản phẩm biệt dược : Imipramin Dak
  • Công ty : Dumex
    Sản phẩm biệt dược : Imiprex
  • Công ty : Incepta
    Sản phẩm biệt dược : Pramin
  • Công ty : Novartis
    Sản phẩm biệt dược : Tofranil
  • Công ty :
    Sản phẩm biệt dược : TOFRANIL-PM
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00458
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=3696
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46507351
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07049
ChemSpider
http://www.chemspider.com/Chemical-Structure.3568.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/53489-330-07
PharmGKB
http://www.pharmgkb.org/drug/PA449969
Wikipedia
http://en.wikipedia.org/wiki/Imipramine
RxList
http://www.rxlist.com/cgi/generic/imip.htm
PDRhealth
http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/tof1448.shtml
Drugs.com
http://www.drugs.com/cdi/imipramine.html
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