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Namespace Prefixes

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Statements

Subject Item
n2:DB00321
rdf:type
n3:Drug
n3:description
Amitriptyline hydrochloride 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, amitriptyline does not affect mood or arousal, but may cause sedation. In depressed individuals, amitriptyline exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Tertiary amine TCAs, such as amitriptyline, are more potent inhibitors of serotonin reuptake than secondary amine TCAs, such as nortriptyline. TCAs also down-regulate cerebral cortical &beta;-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-H<sub>1</sub> receptors, &alpha;<sub>1</sub>-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. Amitriptyline 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).
n3:dosage
n9:271B541B-363D-11E5-9242-09173F13E4C5 n9:271B541C-363D-11E5-9242-09173F13E4C5 n9:271B5417-363D-11E5-9242-09173F13E4C5 n9:271B5418-363D-11E5-9242-09173F13E4C5 n9:271B5419-363D-11E5-9242-09173F13E4C5 n9:271B541A-363D-11E5-9242-09173F13E4C5 n9:271B5413-363D-11E5-9242-09173F13E4C5 n9:271B5414-363D-11E5-9242-09173F13E4C5 n9:271B5415-363D-11E5-9242-09173F13E4C5 n9:271B5416-363D-11E5-9242-09173F13E4C5 n9:271B5411-363D-11E5-9242-09173F13E4C5 n9:271B5412-363D-11E5-9242-09173F13E4C5
n3:generalReferences
# Otaka M, Jin M, Odashima M, Matsuhashi T, Wada I, Horikawa Y, Komatsu K, Ohba R, Oyake J, Hatakeyama N, Watanabe S: New strategy of therapy for functional dyspepsia using famotidine, mosapride and amitriptyline. Aliment Pharmacol Ther. 2005 Jun;21 Suppl 2:42-6. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/15943846
n3:group
approved
n3:halfLife
10 to 50 hours, with an average of 15 hours
n3:indication
For the treatment of depression, chronic pain, irritable bowel syndrome, sleep disorders, diabetic neuropathy, agitation and insomnia, and migraine prophylaxis.
n3:manufacturer
n8:271B53EE-363D-11E5-9242-09173F13E4C5 n8:271B5401-363D-11E5-9242-09173F13E4C5 n8:271B5402-363D-11E5-9242-09173F13E4C5 n8:271B53FF-363D-11E5-9242-09173F13E4C5 n8:271B5400-363D-11E5-9242-09173F13E4C5 n8:271B5405-363D-11E5-9242-09173F13E4C5 n8:271B5403-363D-11E5-9242-09173F13E4C5 n8:271B5404-363D-11E5-9242-09173F13E4C5 n8:271B53F9-363D-11E5-9242-09173F13E4C5 n8:271B53FA-363D-11E5-9242-09173F13E4C5 n8:271B53F7-363D-11E5-9242-09173F13E4C5 n8:271B53F8-363D-11E5-9242-09173F13E4C5 n8:271B53FD-363D-11E5-9242-09173F13E4C5 n8:271B53FE-363D-11E5-9242-09173F13E4C5 n8:271B53FB-363D-11E5-9242-09173F13E4C5 n8:271B53FC-363D-11E5-9242-09173F13E4C5 n8:271B53F1-363D-11E5-9242-09173F13E4C5 n8:271B53F2-363D-11E5-9242-09173F13E4C5 n8:271B53EF-363D-11E5-9242-09173F13E4C5 n8:271B53F0-363D-11E5-9242-09173F13E4C5 n8:271B53F5-363D-11E5-9242-09173F13E4C5 n8:271B53F6-363D-11E5-9242-09173F13E4C5 n8:271B53F3-363D-11E5-9242-09173F13E4C5 n8:271B53F4-363D-11E5-9242-09173F13E4C5
owl:sameAs
n7:DB00321 n18:DB00321
dcterms:title
Amitriptyline
adms:identifier
n16:Amitriptyline n21:53489-104-07 n22:PA448385 n23:200 n24:C06824 n25:2160 n26:46508798 n27:2666 n29:200 n30:2075 n31:DB00321
n3:mechanismOfAction
Amitriptyline is metabolized to nortriptyline which inhibits the reuptake of norepinephrine and serotonin almost equally. Amitriptyline inhibits the membrane pump mechanism responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons. Pharmacologically this action may potentiate or prolong neuronal activity since reuptake of these biogenic amines is important physiologically in terminating transmitting activity. This interference with the reuptake of norepinephrine and/or serotonin is believed by some to underlie the antidepressant activity of amitriptyline.
n3:packager
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n3:routeOfElimination
Virtually the entire dose is excreted as glucuronide or sulfate conjugate of metabolites, with little unchanged drug appearing in the urine. 25-50% of a single orally administered dose is excreted in urine as inactive metabolites within 24 hours. Small amounts are excreted in feces via biliary elimination.
n3:synonym
Amitriptilina 5-(3-Dimethylaminopropylidene)-10,11-dihydro-5H-dibenzo(a,D)cycloheptatriene 10,11-dihydro-5-(gamma-Dimethylaminopropylidene)-5H-dibenzo(a,D)cycloheptene 5-(3-Dimethylaminopropylidene)-10,11-dihydro-5H-dibenzo(a,D)cycloheptene 5-(gamma-Dimethylaminopropylidene)-5H-dibenzo[a,D][1,4]cycloheptadiene 3-(10,11-dihydro-5H-Dibenzo[a,D]cyclohepten-5-ylidene)-N,N-dimethylpropan-1-amine 3-(10,11-dihydro-5H-Dibenzo(a,D)cyclohepten-5-ylidene)-N,N-dimethyl-1-propanamine Amitriptyline 10,11-dihydro-N,N-Dimethyl-5H-dibenzo(a,D)heptalene-delta(5),gamma-propylamine Amitriptylinum Amitriptylin
n3:toxicity
LD<sub>50</sub>=350 mg/kg (in mice). Symptoms of overdose include abnormally low blood pressure, confusion, convulsions, dilated pupils and other eye problems, disturbed concentration, drowsiness, hallucinations, impaired heart function, rapid or irregular heartbeat, reduced body temperature, stupor, and unresponsiveness or coma. 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.
n12:hasAHFSCode
n20:28-16-04-28
n3:foodInteraction
Avoid St.John's Wort. Avoid alcohol. Take with food to reduce irritation. Avoid excessive quantities of coffee or tea (caffeine).
n3:mixture
n19:271B53AB-363D-11E5-9242-09173F13E4C5 n19:271B53AC-363D-11E5-9242-09173F13E4C5 n19:271B53AF-363D-11E5-9242-09173F13E4C5 n19:271B53AD-363D-11E5-9242-09173F13E4C5 n19:271B53AE-363D-11E5-9242-09173F13E4C5
n3:proteinBinding
Very highly protein bound (90% or more) in plasma and tissues
n3:salt
n3:synthesisReference
Manfred Durr, Benedikt Gajdos, Klaus-Dieter Gneuss, Ekkehard Harhausen, Jurgen Seidel, "Pharmaceutical amitriptylin oxide preparation and process for its manufacture." U.S. Patent US4567202, issued January 28, 1986.
n10:hasConcept
n11:M0000975
foaf:page
n5:amitriptyline.html n32:amitrip.htm
n3:IUPAC-Name
n14:271B5421-363D-11E5-9242-09173F13E4C5
n3:InChI
n14:271B5427-363D-11E5-9242-09173F13E4C5
n3:Molecular-Formula
n14:271B5426-363D-11E5-9242-09173F13E4C5
n3:Molecular-Weight
n14:271B5423-363D-11E5-9242-09173F13E4C5
n3:Monoisotopic-Weight
n14:271B5424-363D-11E5-9242-09173F13E4C5
n3:SMILES
n14:271B5425-363D-11E5-9242-09173F13E4C5
n3:Water-Solubility
n14:271B541F-363D-11E5-9242-09173F13E4C5 n14:271B5436-363D-11E5-9242-09173F13E4C5
n3:logP
n14:271B5420-363D-11E5-9242-09173F13E4C5 n14:271B541D-363D-11E5-9242-09173F13E4C5 n14:271B5438-363D-11E5-9242-09173F13E4C5
n3:logS
n14:271B541E-363D-11E5-9242-09173F13E4C5 n14:271B5439-363D-11E5-9242-09173F13E4C5
n3:pKa
n14:271B543A-363D-11E5-9242-09173F13E4C5
n12:hasATCCode
n13:N06AA09
n3:H-Bond-Acceptor-Count
n14:271B542D-363D-11E5-9242-09173F13E4C5
n3:H-Bond-Donor-Count
n14:271B542E-363D-11E5-9242-09173F13E4C5
n3:InChIKey
n14:271B5428-363D-11E5-9242-09173F13E4C5
n3:Polar-Surface-Area--PSA-
n14:271B5429-363D-11E5-9242-09173F13E4C5
n3:Polarizability
n14:271B542B-363D-11E5-9242-09173F13E4C5
n3:Refractivity
n14:271B542A-363D-11E5-9242-09173F13E4C5
n3:Rotatable-Bond-Count
n14:271B542C-363D-11E5-9242-09173F13E4C5
n3:absorption
Rapidly and well absorbed following oral administration (bioavailability is 30-60% due to first pass metabolism). Peak plasma concentrations occur 2-12 hours following oral or intramuscular administration.
n3:affectedOrganism
Humans and other mammals
n3:casRegistryNumber
50-48-6
n3:category
n3:containedIn
n17:271B5406-363D-11E5-9242-09173F13E4C5 n17:271B540D-363D-11E5-9242-09173F13E4C5 n17:271B540E-363D-11E5-9242-09173F13E4C5 n17:271B540B-363D-11E5-9242-09173F13E4C5 n17:271B540C-363D-11E5-9242-09173F13E4C5 n17:271B5409-363D-11E5-9242-09173F13E4C5 n17:271B540A-363D-11E5-9242-09173F13E4C5 n17:271B5407-363D-11E5-9242-09173F13E4C5 n17:271B5408-363D-11E5-9242-09173F13E4C5 n17:271B540F-363D-11E5-9242-09173F13E4C5 n17:271B5410-363D-11E5-9242-09173F13E4C5
n3:Bioavailability
n14:271B5432-363D-11E5-9242-09173F13E4C5
n3:Ghose-Filter
n14:271B5434-363D-11E5-9242-09173F13E4C5
n3:MDDR-Like-Rule
n14:271B5435-363D-11E5-9242-09173F13E4C5
n3:Melting-Point
n14:271B5437-363D-11E5-9242-09173F13E4C5
n3:Number-of-Rings
n14:271B5431-363D-11E5-9242-09173F13E4C5
n3:Physiological-Charge
n14:271B5430-363D-11E5-9242-09173F13E4C5
n3:Rule-of-Five
n14:271B5433-363D-11E5-9242-09173F13E4C5
n3:Traditional-IUPAC-Name
n14:271B5422-363D-11E5-9242-09173F13E4C5
n3:pKa--strongest-basic-
n14:271B542F-363D-11E5-9242-09173F13E4C5