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药品详细

Nortriptyline(去甲替林)

化学结构式图
中文名
去甲替林
英文名
Nortriptyline
分子式
C19H21N
化学名
methyl({3-[(2E)-tricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ylidene]propyl})amine
分子量
Average: 263.3767
Monoisotopic: 263.167399677
CAS号
72-69-5
ATC分类
N06A 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

Nortriptyline hydrochloride, the N-demethylated active metabolite of amitriptyline, is a dibenzocycloheptene-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, nortriptyline does not affect mood or arousal, but may cause sedation. In depressed individuals, nortriptyline exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Secondary amine TCAs, such as nortriptyline, are more potent inhibitors of norepinephrine reuptake than tertiary amine TCAs, such as amitriptyline. 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. Nortriptyline exerts less anticholinergic and sedative side effects compared to the tertiary amine TCAs, amitriptyline and clomipramine. Nortriptyline may be used to treat depression, chronic pain (unlabeled use), irritable bowel syndrome (unlabeled use), diabetic neuropathy (unlabeled use), post-traumatic stress disorder (unlabeled use), and for migraine prophylaxis (unlabeled use).

生产厂家
  • Eli lilly and co
  • Mylan pharmaceuticals inc
  • Pharmaceutical assoc inc
  • Ranbaxy pharmaceuticals inc
  • Sandoz inc
  • Taro pharmaceutical industries ltd
  • Taro pharmaceuticals inc
  • Teva pharmaceuticals usa inc
  • Tyco healthcare group lp
  • Watson laboratories inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Prochazka AV, Weaver MJ, Keller RT, Fryer GE, Licari PA, Lofaso D: A randomized trial of nortriptyline for smoking cessation. Arch Intern Med. 1998 Oct 12;158(18):2035-9. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Dibenzocycloheptenes
Substructures
  • Alkanes and Alkenes
  • Aliphatic and Aryl Amines
  • Phenylpropenes
  • Benzene and Derivatives
  • Dibenzocycloheptenes
  • Isoprenes
  • Aromatic compounds
适应症
药理
Indication For the treatment of depression, chronic pain, irritable bowel syndrome, sleep disorders, diabetic neuropathy, agitation and insomnia, and migraine prophylaxis.
Pharmacodynamics Similar to protriptyline, nortriptyline is a tricyclic antidepressant of the dibenzocycloheptene type and is the active metabolite of amitriptyline.
Mechanism of action It is believed that nortriptyline either inhibits the reuptake of the neurotransmitter serotonin at the neuronal membrane or acts at beta-adrenergic receptors. Tricyclic antidepressants do not inhibit monoamine oxidase nor do they affect dopamine reuptake.
Absorption Well absorbed from the GI tract. Peak plasma concentrations occur 7-8.5 hours following oral administration.
Volume of distribution Not Available
Protein binding Highly protein-bound in plasma and tissues.
Metabolism
Undergoes hepatic metabolism via the same pathway as other TCAs.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Nortriptyline
E-10-Hydroxynortriptyline Details
Nortriptyline
Desmethylnortriptyline Details
Route of elimination Approximately one-third of a single orally administered dose is excreted in urine within 24 hours. Small amounts are excreted in feces via biliary elimination.
Half life 16 to 90+ hours
Clearance Not Available
Toxicity Symptoms of overdose include cardiac dysrhythmias, severe hypotension, shock, congestive heart failure, pulmonary edema, convulsions, and CNS depression, including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic antidepressant toxicity. Side effects include: sedation, hypotension, blurred vision, dry mouth, constipation, urinary retention, postural hypotension, tachycardia, hypertension, ECG changes, heart failure, impaired memory and delirium, and precipitation of hypomanic or manic episodes in bipolar depression. Withdrawal symptoms include gastrointestinal disturbances, anxiety, and insomnia.
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
melting point 213-215 °C Not Available
logP 4.51 BRODIN,A (1974)
pKa 10.1 SANGSTER (2004)
Predicted Properties
Property Value Source
water solubility 8.74e-04 g/l ALOGPS
logP 4.65 ALOGPS
logP 4.43 ChemAxon
logS -5.5 ALOGPS
pKa (strongest basic) 10.47 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 1 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 12.03 ChemAxon
rotatable bond count 3 ChemAxon
refractivity 96.21 ChemAxon
polarizability 31.87 ChemAxon
药物相互作用
Drug Interaction
Altretamine Risk of hypotension
Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Atazanavir Atazanavir may increase the effect and toxicity of the tricyclic antidepressant, nortriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if atazanavir if initiated, discontinued or dose changed.
Butabarbital Barbiturates like butabarbital may increase the metabolism of tricyclic antidepressants like nortriptyline. 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 nortriptyline. 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, nortriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if carbamazepine is initiated, discontinued or dose changed.
Cimetidine Cimetidine may increase the effect of the tricyclic antidepressant, nortriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if cimetidine is initiated, discontinued or dose changed.
Cisapride Increased risk of cardiotoxicity and arrhythmias
Clonidine The tricyclic antidepressant, nortriptyline, 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, nortriptyline.
Dobutamine The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of dobutamine.
Donepezil Possible antagonism of action
Dopamine The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of dopamine.
Duloxetine Possible increase in the levels of this agent when used with duloxetine
Ephedra The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of ephedra.
Ephedrine The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of ephedrine.
Epinephrine The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of epinephrine.
Fenoterol The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of fenoterol.
Fluconazole Fluconazole may increase the effect and toxicity of the tricyclic antidepressant, nortriptyline, by decreasing its metabolism. Additive QTc-prolonging effects may also occur. Monitor for changes in the therapeutic and adverse effects of nortriptyline 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, nortriptyline, 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 nortriptyline if fluoxetine is initiated, discontinued or dose changed.
Fluvoxamine The SSRI, fluvoxamine, may increase the serum concentration of the tricyclic antidepressant, nortriptyline, 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 nortriptyline if fluvoxamine is initiated, discontinued or dose changed.
Galantamine Possible antagonism of action
Grepafloxacin Increased risk of cardiotoxicity and arrhythmias
Guanethidine The tricyclic antidepressant, nortriptyline, decreases the effect of guanethidine.
Isocarboxazid Possibility of severe adverse effects
Isoproterenol The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of isoproterenol.
Ketoconazole Ketoconazole, a moderate CYP2D6 inhibitor, may increase the serum concentration of nortriptyline by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if ketoconazole is initiated, discontinued or dose changed.
Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Mephentermine The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of mephentermine.
Metaraminol The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of metaraminol.
Methoxamine The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of methoxamine.
Moclobemide Possible severe adverse reaction with this combination
Norepinephrine The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of norepinephrine.
Orciprenaline The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of orciprenaline.
Phenelzine Possibility of severe adverse effects
Phenylephrine The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of phenylephrine.
Phenylpropanolamine The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of phenylpropanolamine.
Pirbuterol The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of pirbuterol.
Procaterol The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of procaterol.
Pseudoephedrine The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of pseudoephedrine.
Quinidine Additive QTc-prolonging effects may occur. Quinidine may also increase the serum concentration of the tricyclic antidepressant, nortriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline 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 the tricyclic antidepressant, nortriptyline.
Rasagiline Possibility of severe adverse effects
Rifabutin The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, nortriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if rifabutin is initiated, discontinued or dose changed.
Rifampin The rifamycin, rifampin, may decrease the effect of the tricyclic antidepressant, nortriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if rifampin is initiated, discontinued or dose changed.
Ritonavir Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, nortriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if ritonavir if initiated, discontinued or dose changed.
Rivastigmine Possible antagonism of action
Salbutamol The tricyclic antidepressant, nortriptyline, 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, Nortriptyline, 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.
Terbinafine Terbinafine may increase the effect and toxicity of the tricyclic antidepressant, nortriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if terbinafine is initiated, discontinued or dose changed.
Terbutaline The tricyclic antidepressant, nortriptyline, 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.
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.
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 Nortriptyline, 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. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Triprolidine Triprolidine and Nortriptyline, 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 Nortriptyline, 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 nortriptyline, 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).
食物相互作用
  • Avoid alcohol.
  • Avoid excessive quantities of coffee or tea (caffeine).
  • Take with food to reduce irritation.

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