{"id":"maprotiline","rwe":[],"tags":[{"label":"maprotiline","category":"class"},{"label":"Small Molecule","category":"modality"},{"label":"Alpha-1A adrenergic receptor","category":"target"},{"label":"ADRA1A","category":"gene"},{"label":"HRH1","category":"gene"},{"label":"SLC6A2","category":"gene"},{"label":"N06AA21","category":"atc"},{"label":"Off-Patent","category":"patent"},{"label":"Generic Available","category":"availability"},{"label":"Mature","category":"status"},{"label":"Depressive disorder","category":"indication"},{"label":"Mixed anxiety and depressive disorder","category":"indication"},{"label":"Approved 1980s","category":"decade"},{"label":"Adrenergic Agents","category":"pharmacology"},{"label":"Adrenergic Uptake Inhibitors","category":"pharmacology"},{"label":"Antidepressive Agents","category":"pharmacology"},{"label":"Antidepressive Agents, Second-Generation","category":"pharmacology"},{"label":"Central Nervous System Agents","category":"pharmacology"},{"label":"Membrane Transport Modulators","category":"pharmacology"},{"label":"Neurotransmitter Agents","category":"pharmacology"},{"label":"Neurotransmitter Uptake Inhibitors","category":"pharmacology"},{"label":"Psychotropic Drugs","category":"pharmacology"}],"phase":"marketed","safety":{"safetySignals":[{"llr":53.544,"date":"","count":14,"signal":"Polydipsia","source":"DrugCentral FAERS","actionTaken":"Reported 14 times (LLR=54)"},{"llr":52.901,"date":"","count":28,"signal":"Rhabdomyolysis","source":"DrugCentral FAERS","actionTaken":"Reported 28 times (LLR=53)"},{"llr":42.57,"date":"","count":11,"signal":"Decreased interest","source":"DrugCentral FAERS","actionTaken":"Reported 11 times (LLR=43)"},{"llr":41.925,"date":"","count":15,"signal":"Aspiration","source":"DrugCentral FAERS","actionTaken":"Reported 15 times (LLR=42)"},{"llr":37.427,"date":"","count":15,"signal":"Conjunctivitis","source":"DrugCentral FAERS","actionTaken":"Reported 15 times (LLR=37)"},{"llr":36.49,"date":"","count":16,"signal":"Mental disorder","source":"DrugCentral FAERS","actionTaken":"Reported 16 times (LLR=36)"},{"llr":35.666,"date":"","count":17,"signal":"Restlessness","source":"DrugCentral FAERS","actionTaken":"Reported 17 times (LLR=36)"}],"drugInteractions":[{"url":"/drug/isocarboxazid","drug":"isocarboxazid","action":"Avoid combination","effect":"May interact with Isocarboxazid","source":"DrugCentral","drugSlug":"isocarboxazid"},{"url":"/drug/methylthioninium-chloride","drug":"methylthioninium chloride","action":"Avoid combination","effect":"May interact with Methylene Blue","source":"DrugCentral","drugSlug":"methylthioninium-chloride"},{"url":"/drug/phenelzine","drug":"phenelzine","action":"Avoid combination","effect":"May interact with Phenelzine","source":"DrugCentral","drugSlug":"phenelzine"},{"url":"/drug/procarbazine","drug":"procarbazine","action":"Avoid combination","effect":"May interact with Procarbazine","source":"DrugCentral","drugSlug":"procarbazine"},{"url":"/drug/selegiline","drug":"selegiline","action":"Avoid combination","effect":"May interact with Selegiline","source":"DrugCentral","drugSlug":"selegiline"},{"url":"/drug/tranylcypromine","drug":"tranylcypromine","action":"Avoid combination","effect":"May interact with Tranylcypromine","source":"DrugCentral","drugSlug":"tranylcypromine"}],"commonSideEffects":[],"contraindications":["Alcoholism","Angle-closure glaucoma","Bipolar disorder","Central nervous system depression","Cerebrovascular accident","Conduction disorder of the heart","Disease of liver","Disorder of cardiovascular system","Hyperthyroidism","Myocardial infarction","Myocardial infarction in recovery phase","Neutropenic disorder","Ocular hypertension","Retention of urine","Seizure disorder","Sinus tachycardia","Suicidal thoughts","Surgical procedure"]},"trials":[],"aliases":[],"patents":[],"pricing":[],"_sources":{"trials":{"url":"https://clinicaltrials.gov/search?intr=MAPROTILINE","method":"api_direct","source":"ClinicalTrials.gov","rawText":"","confidence":1,"sourceType":"ctgov","retrievedAt":"2026-04-20T03:14:15.392092+00:00"},"regulatory.ca":{"url":"","method":"api_direct","source":"Health Canada DPD","rawText":"","confidence":1,"sourceType":"health_canada_dpd","retrievedAt":"2026-04-20T03:14:21.409867+00:00"},"publicationCount":{"url":"https://pubmed.ncbi.nlm.nih.gov/?term=MAPROTILINE","method":"api_direct","source":"PubMed/NCBI","rawText":"","confidence":1,"sourceType":"pubmed","retrievedAt":"2026-04-20T03:14:21.939994+00:00"},"crossReferences.chemblId":{"url":"https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL21731/","method":"api_direct","source":"ChEMBL (EMBL-EBI)","rawText":"","confidence":1,"sourceType":"chembl","retrievedAt":"2026-04-20T03:14:22.648323+00:00"}},"allNames":["maprotiline","maprotiline hydrochloride","maprotiline HCl"],"offLabel":[],"synonyms":["maprotiline","maprotiline hydrochloride","maprotiline HCl"],"timeline":[{"date":"1980-12-01","type":"positive","source":"DrugCentral","milestone":"FDA approval"},{"date":"1987-12-30","type":"neutral","source":"FDA Orange Book","milestone":"Generic entry — 2 manufacturers approved"}],"aiSummary":"Maprotiline is a small molecule drug that targets the alpha-1A adrenergic receptor. It was originally developed and is currently owned by a pharmaceutical company. Maprotiline is used to treat depressive disorder and mixed anxiety and depressive disorder, and was FDA approved in 1980. The drug is now off-patent and has multiple generic manufacturers. Key safety considerations include its long half-life of 51 hours and moderate bioavailability of 68%.","approvals":[{"date":"1980-12-01","orphan":false,"company":"","regulator":"FDA"}],"ecosystem":[{"indication":"Depressive disorder","otherDrugs":[{"name":"amitriptyline","slug":"amitriptyline","company":"Astrazeneca"},{"name":"amoxapine","slug":"amoxapine","company":"Lederle"},{"name":"bupropion","slug":"bupropion","company":"Glaxosmithkline"},{"name":"citalopram","slug":"citalopram","company":"Forest Labs"}],"globalPrevalence":280000000},{"indication":"Mixed anxiety and depressive disorder","otherDrugs":[{"name":"alprazolam","slug":"alprazolam","company":"Pharmacia And Upjohn"},{"name":"amitriptyline","slug":"amitriptyline","company":"Astrazeneca"},{"name":"chlordiazepoxide","slug":"chlordiazepoxide","company":"Valeant Pharm Intl"},{"name":"perphenazine","slug":"perphenazine","company":""}],"globalPrevalence":280000000}],"mechanism":{"target":"Alpha-1A adrenergic receptor","novelty":"Follow-on","targets":[{"gene":"ADRA1A","source":"DrugCentral","target":"Alpha-1A adrenergic receptor","protein":"Alpha-1A adrenergic receptor"},{"gene":"HRH1","source":"DrugCentral","target":"Histamine H1 receptor","protein":"Histamine H1 receptor"},{"gene":"SLC6A2","source":"DrugCentral","target":"Sodium-dependent noradrenaline transporter","protein":"Sodium-dependent noradrenaline transporter"},{"gene":"HTR2C","source":"DrugCentral","target":"5-hydroxytryptamine receptor 2C","protein":"5-hydroxytryptamine receptor 2C"},{"gene":"CHRM4","source":"DrugCentral","target":"Muscarinic acetylcholine receptor M4","protein":"Muscarinic acetylcholine receptor M4"},{"gene":"CHRM3","source":"DrugCentral","target":"Muscarinic acetylcholine receptor M3","protein":"Muscarinic acetylcholine receptor M3"},{"gene":"CHRM5","source":"DrugCentral","target":"Muscarinic acetylcholine receptor M5","protein":"Muscarinic acetylcholine receptor M5"},{"gene":"HTR2A","source":"DrugCentral","target":"5-hydroxytryptamine receptor 2A","protein":"5-hydroxytryptamine receptor 2A"},{"gene":"ADRA2B","source":"DrugCentral","target":"Alpha-2B adrenergic receptor","protein":"Alpha-2B adrenergic receptor"},{"gene":"CHRM1","source":"DrugCentral","target":"Muscarinic acetylcholine receptor M1","protein":"Muscarinic acetylcholine receptor M1"}],"modality":"Small Molecule","drugClass":"maprotiline","explanation":"","oneSentence":"","technicalDetail":"Maprotiline is a selective norepinephrine reuptake inhibitor (NRI) that also has some anticholinergic and antihistaminic properties, which contribute to its therapeutic effects."},"commercial":{"launchDate":"1980","_launchSource":"DrugCentral (FDA 1980-12-01, )"},"references":[{"id":1,"url":"https://drugcentral.org/drugcard/1634","fields":["approvals","synonyms","ATC","PK","indications","contraindications","DDIs","targets","patents","FAERS"],"source":"DrugCentral"},{"id":2,"url":"https://clinicaltrials.gov/search?intr=MAPROTILINE","fields":["trials"],"source":"ClinicalTrials.gov"},{"id":3,"url":"https://pubmed.ncbi.nlm.nih.gov/?term=MAPROTILINE","fields":["publications"],"source":"PubMed/NCBI"},{"id":4,"url":"https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book-data-files","fields":["patents","exclusivity","genericManufacturers"],"source":"FDA Orange Book"}],"_enrichedAt":"2026-03-30T12:30:13.315230","_validation":{"fieldsValidated":0,"lastValidatedAt":"2026-04-20T03:14:24.217898+00:00","fieldsConflicting":2,"overallConfidence":0.8},"biosimilars":[],"competitors":[{"drugName":"desipramine","drugSlug":"desipramine","fdaApproval":"1964-11-20","genericCount":8,"patentStatus":"Off-patent — generic 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available","relationship":"same-class"},{"drugName":"protriptyline","drugSlug":"protriptyline","fdaApproval":"1967-09-27","genericCount":4,"patentStatus":"Off-patent — generic available","relationship":"same-class"},{"drugName":"doxepin","drugSlug":"doxepin","fdaApproval":"1969-09-23","patentExpiry":"Sep 7, 2030","patentStatus":"Patent protected","relationship":"same-class"},{"drugName":"amoxapine","drugSlug":"amoxapine","fdaApproval":"1980-09-22","genericCount":3,"patentStatus":"Off-patent — generic available","relationship":"same-class"}],"genericName":"maprotiline","indications":{"approved":[{"name":"Depressive disorder","source":"DrugCentral","snomedId":35489007,"regulator":"FDA","usPrevalence":21000000,"globalPrevalence":280000000,"prevalenceMethod":"curated","prevalenceSource":"WHO, 2023"},{"name":"Mixed anxiety and depressive 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patents","relatedDrugs":[{"drugId":"desipramine","brandName":"desipramine","genericName":"desipramine","approvalYear":"1964","relationship":"same-class"},{"drugId":"imipramine","brandName":"imipramine","genericName":"imipramine","approvalYear":"1959","relationship":"same-class"},{"drugId":"clomipramine","brandName":"clomipramine","genericName":"clomipramine","approvalYear":"1989","relationship":"same-class"},{"drugId":"trimipramine","brandName":"trimipramine","genericName":"trimipramine","approvalYear":"1979","relationship":"same-class"},{"drugId":"amitriptyline","brandName":"amitriptyline","genericName":"amitriptyline","approvalYear":"1961","relationship":"same-class"},{"drugId":"nortriptyline","brandName":"nortriptyline","genericName":"nortriptyline","approvalYear":"1964","relationship":"same-class"},{"drugId":"protriptyline","brandName":"protriptyline","genericName":"protriptyline","approvalYear":"1967","relationship":"same-class"},{"drugId":"doxepin","brandName":"doxepin","genericName":"doxepin","approvalYear":"1969","relationship":"same-class"},{"drugId":"amoxapine","brandName":"amoxapine","genericName":"amoxapine","approvalYear":"1980","relationship":"same-class"}],"trialDetails":[{"nctId":"NCT04200066","phase":"PHASE1","title":"A Study of Maprotiline in Combination With Tamoxifen and Temozolomide for Recurrent Glioblastoma","status":"WITHDRAWN","sponsor":"University of Rochester","startDate":"2022-06-01","conditions":["Glioblastoma","Brain Tumor"],"enrollment":0,"completionDate":"2024-02-01"},{"nctId":"NCT02374567","phase":"PHASE3","title":"Pharmacovigilance in Gerontopsychiatric Patients","status":"TERMINATED","sponsor":"Hannover Medical School","startDate":"2015-01","conditions":["Dementia","Depression","Schizophrenia","Psychosomatic Disorders","Anxiety Disorders"],"enrollment":407,"completionDate":"2017-06-28"},{"nctId":"NCT02873234","phase":"","title":"A Study of Chinese Medicine Treating Depression","status":"UNKNOWN","sponsor":"The Third Affiliated Hospital of Beijing University of Chinese Medicine","startDate":"2016-06","conditions":["Depression"],"enrollment":4600,"completionDate":"2020-05"},{"nctId":"NCT00704860","phase":"PHASE4","title":"Treatment-Resistant Depression, Hippocampus Atrophy and Serotonin Genetic Polymorphism","status":"COMPLETED","sponsor":"University of Ottawa","startDate":"2005-02","conditions":["Major Depression"],"enrollment":27,"completionDate":"2010-12"}],"genericFilers":[],"latestUpdates":[],"manufacturing":[],"_patentsChecked":true,"crossReferences":{"NUI":"N0000147895","MMSL":"1567","NDDF":"001510","UNII":"2U1W68TROF","VUID":"4019806","CHEBI":"CHEBI:6690","VANDF":"4018785","INN_ID":"2763","RXNORM":"203126","UMLSCUI":"C0024778","chemblId":"CHEMBL21731","ChEMBL_ID":"CHEMBL21731","KEGG_DRUG":"D00818","DRUGBANK_ID":"DB00934","PUBCHEM_CID":"4011","SNOMEDCT_US":"10424009","IUPHAR_LIGAND_ID":"2402","SECONDARY_CAS_RN":"10347-81-6","MESH_DESCRIPTOR_UI":"D008376"},"formularyStatus":[],"_enricherVersion":"v2","_offLabelChecked":true,"developmentCodes":[],"ownershipHistory":[],"pharmacokinetics":{"source":"DrugCentral","halfLife":"51.0 hours","clearance":"14.0 mL/min/kg","bioavailability":"68%","fractionUnbound":"0.11%","volumeOfDistribution":"45.0 L/kg"},"publicationCount":1068,"therapeuticAreas":["Neuroscience"],"atcClassification":{"source":"DrugCentral","atcCode":"N06AA21","allCodes":["N06AA21"]},"biosimilarFilings":[],"recentPublications":[],"companionDiagnostics":[],"genericManufacturers":4,"_genericFilersChecked":true,"genericManufacturerList":["Am Therap","Heritage Pharma","Rising","Watson Labs"],"status":"approved","brandName":"MAPROTILINE","companyName":"","companyId":"","modality":"Small molecule","firstApprovalDate":"1980","enrichmentLevel":3,"visitCount":0,"regulatoryByCountry":[{"country_code":"US","regulator":"FDA","status":"approved","approval_date":"1980-12-01T00:00:00.000Z","mah":"","brand_name_local":null,"application_number":""},{"country_code":"CA","regulator":"Health 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