Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Maprotiline: Difference between pages

{{Short description|Antidepressant}}

{{cs1 config|name-list-style=vanc}}

{{infobox drug

| Watchedfields = changed

| verifiedrevid = 477169275

| IUPAC_name = ''N''-Methyl-9,10-ethanoanthracene-9(10''H'')-propanamine

| image = Maprotiline structure.svg

| width = 200px

| image2 = Maprotiline ball-and-stick model.png

| width2 = 200px

| tradename = Ludiomil, others

| pregnancy_US_comment = B3^{[in US?]}<!-- B3 is AU? -->

| legal_AU = S4

| legal_BR = C1

| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=2023-04-04}}</ref>

| legal_US = Rx-only

| routes_of_administration = [[Oral administration|Oral]], [[intramuscular injection|intramuscular]], [[intravenous therapy|intravenous]]

| bioavailability = 66–70%

| onset = 6 hours

| elimination_half-life = 27–58 hours

| excretion = [[Urine]] (57%) and [[bile]] (30%) as [[glucuronide]]s, 3–4% as unchanged drug

| CAS_supplemental = <br />10347-81-6 ([[hydrochloride]])<br /> 58902-67-3 ([[mesylate]])

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID = 23719117

| synonyms = Maprotiline hydrochloride; Maprotiline methanesulfonate; Ba 34276<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="Drugs.com" />

| SMILES = CNCCC[C@]12CC[C@H](c3ccccc31)c1ccccc12

| StdInChI_Ref = {{stdinchicite|changed|chemspider}}

| StdInChI = 1S/C20H23N/c1-21-14-6-12-20-13-11-15(16-7-2-4-9-18(16)20)17-8-3-5-10-19(17)20/h2-5,7-10,15,21H,6,11-14H2,1H3/t15-,20+

| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}

| StdInChIKey = QSLMDECMDJKHMQ-GSXCWMCISA-N

'''Maprotiline''', sold under the brand name '''Ludiomil''' among others, is a [[tetracyclic antidepressant]] (TeCA) that is used in the treatment of [[depression (mood)|depression]].<ref name="LemkeWilliams2012" /> It may alternatively be classified as a [[tricyclic antidepressant]] (TCA), specifically a [[secondary amine]].<ref name="LemkeWilliams2012" /> In terms of its [[chemistry]] and [[pharmacology]], maprotiline is closely related to such-other secondary-amine TCAs as [[nortriptyline]] and [[protriptyline]] and has similar effects to them,<ref name="Zhou2013" /><ref name="LemkeWilliams2012" /> albeit with more distinct [[anxiolytic]] effects.<ref>{{cite journal | vauthors = Guimarães FS, Zuardi AW, Graeff FG | title = Effect of chlorimipramine and maprotiline on experimental anxiety in humans | journal = Journal of Psychopharmacology | volume = 1 | issue = 3 | pages = 184–192 | date = January 1987 | doi = 10.1177/026988118700100305 | pmid = 22158980 | s2cid = 8444656 }}</ref><ref>{{cite journal | vauthors = Vinader-Caerols C, Martos AJ, Monleón S, Arenas MC, Parra A | title = Acute effects of maprotiline on learning, anxiety, activity and analgesia in male and female mice | journal = Acta Neurobiologiae Experimentalis | date = 2006 | volume = 66 | issue = 1 | pages = 23–31 | doi = 10.55782/ane-2006-1584 | pmid = 16617674 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Pecknold JC, Familamiri P, McClure DJ, Elie R, Chang H | title = Trimipramine and maprotiline: antidepressant, anxiolytic, and cardiotoxic comparison | journal = The Journal of Clinical Psychiatry | volume = 46 | issue = 5 | pages = 166–171 | date = May 1985 | pmid = 2859273 }}</ref> Additionally, whereas [[protriptyline]] tends to be somewhat more stimulating and in any case is distinctly more-or-less non-sedating,<ref name="pmid6360257">{{cite journal | vauthors = Brownell LG, Perez-Padilla R, West P, Kryger MH | title = The role of protriptyline in obstructive sleep apnea | journal = Bulletin Européen de Physiopathologie Respiratoire | volume = 19 | issue = 6 | pages = 621–4 | date = 1983 | pmid = 6360257 | doi = | url = }}</ref> mild degrees of sedation may be experienced with maprotiline.<ref name="pmid3044007">{{cite journal | vauthors = Holmberg G | title = Sedative effects of maprotiline and amitriptyline | journal = Acta Psychiatrica Scandinavica | volume = 77 | issue = 5 | pages = 584–6 | date = May 1988 | pmid = 3044007 | doi = 10.1111/j.1600-0447.1988.tb05171.x | s2cid = 41977086 | url = }}</ref>

==Medical uses==

Maprotiline is used in the treatment of depression, such as depression associated with agitation or anxiety and has similar efficacy to the antidepressant drug [[moclobemide]].<ref name="pmid8557884">{{cite journal | vauthors = Delini-Stula A, Mikkelsen H, Angst J | title = Therapeutic efficacy of antidepressants in agitated anxious depression--a meta-analysis of moclobemide studies | journal = Journal of Affective Disorders | volume = 35 | issue = 1–2 | pages = 21–30 | date = October 1995 | pmid = 8557884 | doi = 10.1016/0165-0327(95)00034-K }}</ref> This finding has also been validated by a group of [[general practitioner]]s who compared the respective efficacy and tolerability of maprotiline and [[moclobemide]].<ref name="pmid7954482">{{cite journal | vauthors = Gachoud JP, Dick P, Köhler M | title = Comparison of the efficacy and tolerability of moclobemide and maprotiline in depressed patients treated by general practitioners | journal = Clinical Neuropharmacology | volume = 17 | issue = Suppl 1| pages = S29–37 | date = 1994 | pmid = 7954482 | doi = 10.1097/00002826-199417001-00005 | s2cid = 260560762 | url = }}</ref>

* Treatment of [[clinical depression|depression]] of all forms and severities ([[Endogenous depression|endogenous]], [[Psychotic depression|psychotic]], [[Involutional melancholia|involutional]], and [[Neurotic depression|neurotic]]), especially depression associated with agitation or anxiety

* [[Panic disorder]]

* [[Neuropathic pain]], including painful [[polyneuropathy]] in diabetics and non-diabetics alike.<ref name="pmid9430812">{{cite journal | vauthors = Vrethem M, Boivie J, Arnqvist H, Holmgren H, Lindström T, Thorell LH | title = A comparison a amitriptyline and maprotiline in the treatment of painful polyneuropathy in diabetics and nondiabetics | journal = The Clinical Journal of Pain | volume = 13 | issue = 4 | pages = 313–23 | date = December 1997 | pmid = 9430812 | doi = 10.1097/00002508-199712000-00009 }}</ref>

* Treatment of the depressive phase of [[bipolar disorder|bipolar affective disorder]]

* For the symptomatic relief of [[anxiety]], [[stress (medicine)|tension]] or [[insomnia]]

The use of maprotiline in the treatment of [[enuresis]] in [[pediatric]] patients has so far not been systematically explored and its use is not recommended.<ref name = DrugDex /> Safety and effectiveness in the pediatric population in general have not been established. Anyone considering the use of maprotiline in a child or adolescent must balance the potential risks with the clinical need.

A very small body of research has also explored the potential of maprotiline in treating [[diabetic nephropathy|diabetic kidney disease]]<ref>Zhou, Z. and Liu, S., 2022. Maprotiline Ameliorates High Glucose-Induced Dysfunction in Renal Glomerular Endothelial Cells. Experimental and Clinical Endocrinology & Diabetes, 130(09), pp.596-603.</ref> and it has been measured against [[amitriptyline]] in this regard.<ref name="pmid24373831">{{cite journal | vauthors = Singh R, Kishore L, Kaur N | title = Diabetic peripheral neuropathy: current perspective and future directions | journal = Pharmacological Research | volume = 80 | issue = | pages = 21–35 | date = February 2014 | pmid = 24373831 | doi = 10.1016/j.phrs.2013.12.005 | s2cid = 6097534 }}</ref>

Maprotiline and [[fluoxetine]] have also been found, among certain lines of research, to have quite potent anti-profilerative effects against certain forms of cancer of the [[Burkitt lymphoma]] type.<ref name="pmid20141432">{{cite journal | vauthors = Cloonan SM, Drozgowska A, Fayne D, Williams DC | title = The antidepressants maprotiline and fluoxetine have potent selective antiproliferative effects against Burkitt lymphoma independently of the norepinephrine and serotonin transporters | journal = Leukemia & Lymphoma | volume = 51 | issue = 3 | pages = 523–39 | date = March 2010 | pmid = 20141432 | doi = 10.3109/10428190903552112 | s2cid = 33104465 | url = }}</ref><ref name="pmid20503272">{{cite journal | vauthors = Cloonan SM, Williams DC | title = The antidepressants maprotiline and fluoxetine induce Type II autophagic cell death in drug-resistant Burkitt's lymphoma | journal = International Journal of Cancer | volume = 128 | issue = 7 | pages = 1712–23 | date = April 2011 | pmid = 20503272 | doi = 10.1002/ijc.25477 | s2cid = 24955263 | url = }}</ref> One study also bore ought a certain level of evidence regarding maprotiline’s ability to suppress both [[cholesterol]] biosynthesis and [[hepatocellular carcinoma]] liver-cancer progression.

Maprotiline was also measured against [[imipramine]], [[fluoxetine]] and [[ketamine]] in an experiment-model involving two different kinds of [[chicken]] differently-conditioned against [[Stress (biology)|stress]], including (black) [[Australorp]]s in the proposed treatment of treatment-resistant depression in humans.<ref name="pmid24157688">{{cite journal | vauthors = Sufka KJ, White SW | title = Identification of a treatment-resistant, ketamine-sensitive genetic line in the chick anxiety-depression model | journal = Pharmacology, Biochemistry, and Behavior | volume = 113 | issue = | pages = 63–7 | date = November 2013 | pmid = 24157688 | doi = 10.1016/j.pbb.2013.10.013 | s2cid = 23648185 | url = }}</ref>

In general, lower dosages are recommended for patients over 60 years of age. Dosages of 50&nbsp;mg to 75&nbsp;mg daily are usually satisfactory as maintenance therapy for elderly patients who do not tolerate higher amounts.<ref>{{cite web |url=https://www.nlm.nih.gov/medlineplus/druginfo/meds/a682158.html |title=Maprotiline: MedlinePlus Drug Information |website=www.nlm.nih.gov |access-date=29 September 2013}}</ref><ref>{{cite web |url=https://www.drugs.com/pro/maprotiline.html |title=Maprotiline - FDA prescribing information, side effects and uses |website=www.drugs.com |access-date=29 September 2013 |archive-date=30 December 2019 |archive-url=https://web.archive.org/web/20191230233959/https://www.drugs.com/pro/maprotiline.html |url-status=dead }}</ref> In any case, 225 m.g./d. is the absolute-maximum highest recommended dose for this drug, as any more can predispose more significantly to seizures. 150 m.g. is the average optimal daily dose for otherwise-healthy patients who can tolerate a full dose.

===Available forms===

* Coated tablets: 10&nbsp;mg, 25&nbsp;mg, 50&nbsp;mg, and 75&nbsp;mg

* Injectable concentrate, 25&nbsp;mg

==Contraindications==

In generalised theory, maprotiline (as with other tricyclic antidepressants, besides [[trimipramine]]<ref name="pmid8863001">{{cite journal | vauthors = Berger M, Gastpar M | title = Trimipramine: a challenge to current concepts on antidepressives | journal = European Archives of Psychiatry and Clinical Neuroscience | volume = 246 | issue = 5 | pages = 235–9 | date = 1996 | pmid = 8863001 | doi = 10.1007/BF02190274 | s2cid = 29596291 | url = }}</ref><ref name="pmid1979173">{{cite journal | vauthors = Eikmeier G, Muszynski K, Berger M, Gastpar M | title = High-dose trimipramine in acute schizophrenia. Preliminary results of an open trial | journal = Pharmacopsychiatry | volume = 23 | issue = 5 | pages = 212–4 | date = September 1990 | pmid = 1979173 | doi = 10.1055/s-2007-1014510 | s2cid = 5719177 | url = }}</ref><ref name="pmid1806621">{{cite journal | vauthors = Eikmeier G, Berger M, Lodemann E, Muszynski K, Kaumeier S, Gastpar M | title = Trimipramine--an atypical neuroleptic? | journal = International Clinical Psychopharmacology | volume = 6 | issue = 3 | pages = 147–53 | date = 1991 | pmid = 1806621 | doi = 10.1097/00004850-199100630-00003 | s2cid = 41564511 | url = }}</ref> and possibly [[clomipramine]]) may somewhat worsen certain features of schizophrenia, necessitating caution in prescribing them to someone with it and continuation of the antipsychotic treatment (e.g., with [[risperidone]] or [[olanzapine]]). However, certain bodies of evidence have found maprotiline a useful augment in treating some of the ''negative'', or "anaesthetic", symptoms of schizophrenia and in probable extension pronounced [[schizoid personality disorder|''schizoidia'']] (including the characteristic deterioration in personal grooming/appearance).<ref name="pmid2570687">{{cite journal | vauthors = Yamagami S, Soejima K | title = Effect of maprotiline combined with conventional neuroleptics against negative symptoms of chronic schizophrenia | journal = Drugs Under Experimental and Clinical Research | volume = 15 | issue = 4 | pages = 171–6 | date = 1989 | pmid = 2570687 | doi = | url = }}</ref><ref name="pmid6105762">{{cite journal | vauthors = Waehrens J, Gerlach J | title = Antidepressant drugs in anergic schizophrenia. A double-blind cross-over study with maprotiline and placebo | journal = Acta Psychiatrica Scandinavica | volume = 61 | issue = 5 | pages = 438–44 | date = May 1980 | pmid = 6105762 | doi = 10.1111/j.1600-0447.1980.tb00882.x | s2cid = 40809634 | url = }}</ref> It has also been weighed against [[fluvoxamine]] in this overall regard (i.e., treating the ''negative symptoms'' of schizophrenia),<ref name="pmid9617979">{{cite journal | vauthors = Silver H, Shmugliakov N | title = Augmentation with fluvoxamine but not maprotiline improves negative symptoms in treated schizophrenia: evidence for a specific serotonergic effect from a double-blind study | journal = Journal of Clinical Psychopharmacology | volume = 18 | issue = 3 | pages = 208–11 | date = June 1998 | pmid = 9617979 | doi = 10.1097/00004714-199806000-00005 | url = }}</ref> with [[fluvoxamine]] evidencing clear superiority therein. Maprotiline, however, may be specifically useful for the "negative symptom" of [[alogia]] (poverty of thought and/or speech) and in this regard was found demonstrably superior to the other control-drugs ([[alprazolam]], [[bromocriptine]], [[citalopram]], [[fluoxetine]], [[fluvoxamine]], [[nortriptyline]]) in one study.<ref name=Shafti2005>{{cite web|url=http://www.psychosocial.com/IJPR_10/Drug_Specific_Responses_Shafti_Rey_Abad.html| vauthors = Shafti SS, Rey A, Abad A |year=2005|title=Drug – Specific Responsiveness of Negative Symptoms.|publisher=International Journal of Psychosocial Rehabilitation|pages=10 (1), 43–51|url-status=dead|archive-url=https://web.archive.org/web/20120712070130/http://www.psychosocial.com/IJPR_10/Drug_Specific_Responses_Shafti_Rey_Abad.html|archive-date=2012-07-12|access-date=2012-04-29}}</ref> [[Citalopram]], [[clomipramine]] and [[fluvoxamine]] appeared particularly useful in the study for reducing ''affective blunting'', with [[alprazolam]] (Xanax) and maprotiline ranking joint-next.

Patients with [[bipolar affective disorder]] should not receive antidepressants whilst in a manic phase (including [[hypomania]]) under any circumstances whatsoever. (By the same analogy, people with [[schizoaffective disorder]], bipolar type should not be taking maprotiline or other antidepressants while manic.) This is because antidepressants are known to come with the risk of worsening acute mania or precipitating it in so vulnerably-predisposed people.<ref name="pmid1528960">{{cite journal | vauthors = Benazzi F, Mazzoli M, Rossi E | title = Severe mania after maprotiline-induced coma | journal = Pharmacopsychiatry | volume = 25 | issue = 4 | pages = 207 | date = July 1992 | pmid = 1528960 | doi = 10.1055/s-2007-1014407 | s2cid = 260253520 | url = }}</ref><ref name="pmid3314536">{{cite journal | vauthors = Wehr TA, Goodwin FK | title = Can antidepressants cause mania and worsen the course of affective illness? | journal = The American Journal of Psychiatry | volume = 144 | issue = 11 | pages = 1403–11 | date = November 1987 | pmid = 3314536 | doi = 10.1176/ajp.144.11.1403 | url = }}</ref>

They ([[antidepressants]]) may also negatively interfere with the treatment of mixed bipolar states (pure or [[schizoaffective disorder|schizo-affective]]), where [[electro-convulsive therapy]]<ref name="pmid28503107">{{cite journal | vauthors = Perugi G, Medda P, Toni C, Mariani MG, Socci C, Mauri M | title = The Role of Electroconvulsive Therapy (ECT) in Bipolar Disorder: Effectiveness in 522 Patients with Bipolar Depression, Mixed-state, Mania and Catatonic Features | journal = Current Neuropharmacology | volume = 15 | issue = 3 | pages = 359–371 | date = April 2017 | pmid = 28503107 | pmc = 5405614 | doi = 10.2174/1570159X14666161017233642 | url = }}</ref><ref name="pmid22706421">{{cite journal | vauthors = Kuzman MR, Medved V, Velagic V, Goluza E, Bradas Z | title = The use of electroconvulsive therapy to treat schizoaffective disorder in a patient with pacemaker: a case report | journal = Psychiatria Danubina | volume = 24 | issue = 2 | pages = 211–4 | date = June 2012 | pmid = 22706421 | doi = | url = }}</ref> (generally bilateral), [[sodium valproate|valproate]]<ref name="pmid24359859">{{cite journal | vauthors = Azorin JM, Belzeaux R, Cermolacce M, Kaladjian A, Corréard N, Dassa D, Dubois M, Maurel M, Micoulaud Franchi JA, Pringuey D, Fakra E | title = [Recommendations for the treatment of mixed episodes in current guidelines] | language = French | journal = L'Encephale | volume = 39 | issue = Suppl 3| pages = S185–7 | date = December 2013 | pmid = 24359859 | doi = 10.1016/S0013-7006(13)70120-9 | url = }}</ref> and [[antipsychotics]] prove more beneficial (lithium should not be administered concurrently with [[electro-convulsive therapy|E.C.T.]] treatment, as it may induce severe confusion<ref name="pmid31492631">{{cite journal | vauthors = Patel RS, Bachu A, Youssef NA | title = Combination of lithium and electroconvulsive therapy (ECT) is associated with higher odds of delirium and cognitive problems in a large national sample across the United States | journal = Brain Stimulation | volume = 13 | issue = 1 | pages = 15–19 | date = 2020 | pmid = 31492631 | doi = 10.1016/j.brs.2019.08.012 | s2cid = 201125145 | url = | doi-access = free }}</ref>).<ref name="pmid15898959">{{cite journal | vauthors = Krüger S, Trevor Young L, Bräunig P | title = Pharmacotherapy of bipolar mixed states | journal = Bipolar Disorders | volume = 7 | issue = 3 | pages = 205–15 | date = June 2005 | pmid = 15898959 | doi = 10.1111/j.1399-5618.2005.00197.x | url = }}</ref> However, maprotiline (at a high dose) was put to good use in one particular case, of one young man presenting with what was very-possibly a [[mixed affective state|mixed-manic episode]] with a heavy preponderance of depressive symptoms (appearing as depression with significant [[narcissistic personality disorder|narcissistic]] traits; including ''extrapunitive'' tendencies/blame-shifting, entitlement and interpersonal exploitation; and provisionally considered ''narcissistic depression'').<ref name="pmid23789317">{{cite journal | vauthors = Saito S, Kobayashi T, Kato S | title = [A case of major depressive disorder barely distinguishable from narcissistic personality disorder] | language = Japanese | journal = Seishin Shinkeigaku Zasshi = Psychiatria et Neurologia Japonica | volume = 115 | issue = 4 | pages = 363–71 | date = 2013 | pmid = 23789317 | doi = | url = }}</ref> The maprotiline was combined with [[mirtazapine]] (low-dose), [[sodium valproate]] and [[aripiprazole]].

===Absolute===

* Hypersensitivity to maprotiline or to other TCAs and TeCAs

* [[Hypertrophy]] of the [[prostate gland]] with urine hesitancy

* Closed angle [[glaucoma]]

===Special caution needed===

* Concomitant treatment with a [[MAO inhibitor]]

* Serious impairment of liver and kidney function

* [[Epilepsy]] and other conditions that lower the seizure threshold (active [[brain tumor]]s, [[alcohol withdrawal]], other medications)

* Serious cardiovascular conditions ([[arrhythmias]], heart insufficiency, state after [[myocardial infarction]] etc.)

* Treatment of patients under age 18<ref>Simeon J, Maguire J, Lawrence S (1981). Maprotiline effects in children with enuresis and behavioural disorders. Progress in Neuro-Psychopharmacology 5 ( 5–6), 495–8</ref>

===Suicidal patients===

As with other antidepressants, maprotiline increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of maprotiline or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Maprotiline is not approved for use in pediatric patients.<ref name=MedlinePlus>U.S. National Library of Medicine. Last Reviewed 1 Sept. 2010 [https://www.nlm.nih.gov/medlineplus/druginfo/meds/a682158.html Medline Plus entry for Maprotiline]</ref>

===Pregnancy and lactation===

Reproduction studies have been performed in female laboratory rabbits, mice, and rats at doses up to 1.3, 7, and 9 times the maximum daily human dose respectively and have revealed no evidence of impaired fertility or harm to the fetus due to maprotiline. There are, however, no adequate and well controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Maprotiline is excreted in breast milk. At steady-state, the concentrations in milk correspond closely to the concentrations in whole blood. Caution should be exercised when maprotiline hydrochloride is administered to a nursing woman.

==Side effects==

The side-effect profile is comparable to other TCAs and TeCAS and many of the following are due to [[anticholinergic]] (which are less prominent than those of most TCAs) and [[antihistamine]] effects.<ref name = DrugDex /> Most often seen are:

* [[Dizziness]]

* Drowsiness

* [[Somnolence]]

* [[Fatigue (medical)|Fatigue]]

* [[Xerostomia|Dry mouth]] (and complications of long-term uncontrolled dry mouth such as [[dental caries]])

* [[Constipation]]

* [[Vertigo]]

* [[Nausea]] (rare, incidence of ~2%) and vomiting

* Increased appetite and weight gain

* [[Orthostatic hypotension]], [[hypertension]], [[sinus tachycardia]], [[heart-block]], [[arrhythmias]] and other cardiac effects

* [[Sexual dysfunction]] in men: [[erectile dysfunction|impotence]], [[priapism]], [[delayed ejaculation]], [[anejaculation]], [[Hypoactive sexual disorder|decreased libido]]

* Sexual dysfunction in women: decreased libido, [[vaginal dryness]], [[Dyspareunia|painful sexual intercourse]], [[anorgasmia]]

* Allergic skin reactions such as [[rash]] or [[urticaria]] (more often than with other antidepressants). Rarely, severe skin reactions such as [[erythema multiforme]] can occur.

* [[Photosensitivity]]

* Agitation, confusion

* Induction of [[hypomania]] or [[mania]] in patients with underlying [[bipolar affective disorder]]

* [[Psychotic]] symptoms

* [[Tremor]]

* [[Extrapyramidal symptoms]]

* [[Headache]]

* [[Seizure]]s (at high doses)

* Rare haematological complications: [[leukopenia]] and [[agranulocytosis]] (dangerous fall in white blood cells)

* [[Fever]]

* Urinary retention

Maprotiline causes a strong initial sedation (first 2 to 3 weeks of therapy) and is therefore indicated to treat agitated patients or those with suicidal risks. It causes [[anticholinergic]] side effects (dry mouth, constipation, urinary hesitancy, etc.) with much lower incidence than [[amitriptyline]]. Originally, the manufacturer claimed that maprotiline is better tolerated than other TCAs and TeCAs. However, seizures, leukopenia and skin reactions occur more often with maprotiline than with comparable drugs (e.g., amitriptyline, protriptyline, [[mirtazapine]]). Indeed, [[seizures]] are greater risk for concern with maprotiline than with all other tricyclic antidepressants<ref name="pmid6421394">{{cite journal | vauthors = Knudsen K, Heath A | title = Effects of self poisoning with maprotiline | journal = British Medical Journal (Clinical Research Ed.) | volume = 288 | issue = 6417 | pages = 601–3 | date = February 1984 | pmid = 6421394 | pmc = 1444313 | doi = 10.1136/bmj.288.6417.601 | url = }}</ref> (rising from 75&nbsp;mg, becoming significant at daily doses ≥ 200 m.g.), including [[clomipramine]]. It should thus be prescribed with particular, if not extreme, caution to people with a history of [[epilepsy]]/seizures of any other kind. In any case, the total daily dose should be kept to ≤ 225 milligrams.

Maprotiline has no known potential for abuse and psychological dependence.

===Withdrawal===

Withdrawal symptoms frequently seen when treatment with maprotiline is stopped abruptly (agitation, anxiety, insomnia, sometimes activation of mania or rebound depression) can be avoided by reducing the daily dose of maprotiline gradually by approximately 25% each week. If treatment has to be stopped at once for medical reasons, the use of a benzodiazepine (e.g., lorazepam, clonazepam, diazepam) for a maximum of 4 weeks as needed will usually suppress withdrawal symptoms.

== Interactions ==

Maprotiline does have a wide range of possible interactions. Some are typical for TCAs and TeCAs, others are caused by specific metabolic effects (e.g., high plasma-protein-binding) of maprotiline:

'''Increased drug actions:'''

* Other antidepressants, barbiturates, narcotics, sedating antihistamines, anticonvulsive drugs, [[alcohol (drug)|alcohol]]{{snd}} resulting in increased central depression and necessitating some caution when using any of these drugs alongside maprotiline

* Drugs with potential anti-muscarinic/anti-cholinergic activity (antiparkinsonian agents, [[atropine]], [[amantadine]], [[clozapine]] and [[tricyclic antidepressants]] besides maprotiline){{snd}} resulting in increased anti-muscarinic effects (dry mouth, constipation, etc.)

* Sympathomimetics (also those used in local anesthetics like noradrenaline){{snd}} sympathomimetic effects increased (increased blood-pressure, pulse-rate, paleness of skin, etc.)

* Nitrates and antihypertensives (e.g., beta-blockers){{snd}} increased antihypertensive action with pronounced fall in blood pressure

Although concurrent administration of tricyclic antidepressants (likewise with [[selective serotonin reuptake inhibitors|SSRIs]]) and MAOIs has been considered particularly dangerous, even fatal, across various medical and pharmaceutical lines across the decades, the premise for this line of thinking, although commonly accepted, may be erroneous. Specialist-research into this<ref name="pmid28148312">{{cite journal | vauthors = Gillman K | title = "Much ado about nothing": monoamine oxidase inhibitors, drug interactions, and dietary tyramine | journal = CNS Spectrums | volume = 22 | issue = 5 | pages = 385–387 | date = October 2017 | pmid = 28148312 | doi = 10.1017/S1092852916000651 | s2cid = 206312818 | url = | doi-access = free }}</ref> and practical clinical experience involving the co-administration of tricyclics and MAOIs have suggested that it is only tricyclics with strong specific serotonin-reuptake inhibitory action ([[clomipramine]] and, to a lesser extent, [[imipramine]]) that are dangerous to give in combination with MAOIs. Other antidepressants; which may or may not have a significant serotoninergic background otherwise but either way lack in particularly appreciable reuptake-inhibition therein specifically (e.g., [[mirtazapine]], [[amitriptyline]], [[trazodone]], [[lofepramine]], [[nortriptyline]]); may be safe to take alongside MAOIs, where the likes of [[venlafaxine]], [[selective serotonin reuptake inhibitor|SSRIs]] and [[clomipramine]] are not. With maprotiline, this has been demonstrated to be the case with [[moclobemide]],<ref name="pmid2677241">{{cite journal | vauthors = Laux G, Beckmann H, Classen W, Becker T | title = Moclobemide and maprotiline in the treatment of inpatients with major depressive disorder | journal = Journal of Neural Transmission. Supplementum | volume = 28 | issue = | pages = 45–52 | date = 1989 | pmid = 2677241 | doi = | url = }}</ref> a drug it is often compared and considered somewhat analogous (along certain lines) to, and, tentatively, [[brofaromine]]<ref name="pmid8006248">{{cite journal | vauthors = Hoencamp E, Haffmans PM, Dijken WA, Hoogduin CA, Nolen WA, van Dyck R | title = Brofaromine versus lithium addition to maprotiline. A double-blind study in maprotiline refractory depressed outpatients | journal = Journal of Affective Disorders | volume = 30 | issue = 3 | pages = 219–27 | date = March 1994 | pmid = 8006248 | doi = 10.1016/0165-0327(94)90082-5 | url = }}</ref> (a research-agent MAOI which was never brought to full marketing development). Moclobemide specifically, however, may increase maprptiline plasma-levels<ref name="pmid9271778">{{cite journal | vauthors = König F, Wolfersdorf M, Löble M, Wössner S, Hauger B | title = Trimipramine and maprotiline plasma levels during combined treatment with moclobemide in therapy-resistant depression | journal = Pharmacopsychiatry | volume = 30 | issue = 4 | pages = 125–7 | date = July 1997 | pmid = 9271778 | doi = 10.1055/s-2007-979497 | s2cid = 35570626 | url = }}</ref> and may necessitate dose-modification(s).

In any case, however, it is very-strongly advised that an MAOI is added to the (compatible) tricyclic and not the other way around, as adding a tricyclic to an existing treatment-regime involving an MAOI may significantly increase the risk of going into hypertensive crisis.

'''Decreased drug actions:'''

* [[Guanethidine]], [[reserpine]], [[guanfacine]]: anti-hypertensive effects decreased

* [[Clonidine]]: anti-hypertensive effects decreased and risk of (massive) rebound hypertension.

'''Other types of interaction:'''

* Drugs which induce certain enzymes in the liver, e.g., barbiturates, [[phenytoin]], [[carbamazepine]] and oral anti-conceptive drugs, enhance the elimination of maprotiline and decrease its antidepressant effects. Additionally the blood-concentrations of phenytoin or carbamazepine may be increased, leading to a higher incidents of side effects.

* The concomitant use of maprotiline and [[antipsychotics|neuroleptics]] can lead to increased maprotiline blood-levels and to seizures. Combining maprotiline and thioridazine could induce severe arrhythmias.

* Additionally, increased blood-levels of maprotiline are possible, if certain beta-blocking agents (e.g., [[propranolol]]) are given concomitantly.

* Maprotiline may amplify the actions of [[coumarin]]-type anticoagulants (e.g., [[warfarin]], phenprocoumon). The plasma-prothrombin-activity must be assessed closely in order to avoid overt bleedings.

* Maprotiline can increase the actions of oral antidiabetic drugs (sulfonylureas) and [[insulin]]. Diabetic patients should have regular assessments of their blood-glucose-levels.

* The concomitant application with fluoxetine or fluvoxamine may lead to significantly increased plasma-levels of maprotiline, with a correspondingly (and substantially) incidence of maprotiline side effects. Owing to the long half-lives of fluoxetine and fluvoxamine, this effect may persist for quite-some time.

==Pharmacology==

===Pharmacodynamics===

{| class="wikitable floatright" style="font-size:small;"

|+ Maprotiline<ref name="PDSP">{{cite web | title = PDSP K_i Database | work = Psychoactive Drug Screening Program (PDSP)|author1-link=Bryan Roth | vauthors = Roth BL, Driscol J | publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health | access-date = 7 May 2022 | url = https://pdsp.unc.edu/databases/pdsp.php?receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=Maprotiline&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query}}</ref>

|-

! Site !! K_i (nM) !! Species !! Ref

|-

| {{abbrlink|SERT|Serotonin transporter}} || 5,800 || Human || <ref name="pmid9537821">{{cite journal | vauthors = Tatsumi M, Groshan K, Blakely RD, Richelson E | title = Pharmacological profile of antidepressants and related compounds at human monoamine transporters | journal = European Journal of Pharmacology | volume = 340 | issue = 2–3 | pages = 249–258 | date = December 1997 | pmid = 9537821 | doi = 10.1016/s0014-2999(97)01393-9 }}</ref>

|-

| {{abbrlink|NET|Norepinephrine transporter}} || 11–12 || Human || <ref name="pmid9537821" /><ref name="pmid19836247">{{cite journal | vauthors = Heffernan GD, Coghlan RD, Manas ES, McDevitt RE, Li Y, Mahaney PE, Robichaud AJ, Huselton C, Alfinito P, Bray JA, Cosmi SA, Johnston GH, Kenney T, Koury E, Winneker RC, Deecher DC, Trybulski EJ | display-authors = 6 | title = Dual acting norepinephrine reuptake inhibitors and 5-HT(2A) receptor antagonists: Identification, synthesis and activity of novel 4-aminoethyl-3-(phenylsulfonyl)-1H-indoles | journal = Bioorganic & Medicinal Chemistry | volume = 17 | issue = 22 | pages = 7802–7815 | date = November 2009 | pmid = 19836247 | doi = 10.1016/j.bmc.2009.09.023 }}</ref>

|-

| {{abbrlink|DAT|Dopamine transporter}} || 1,000 || Human || <ref name="pmid9537821" />

|-

| [[5-HT2A receptor|5-HT_2A]] || 51 || Rat || <ref name="pmid8876023">{{cite journal | vauthors = Pälvimäki EP, Roth BL, Majasuo H, Laakso A, Kuoppamäki M, Syvälahti E, Hietala J | title = Interactions of selective serotonin reuptake inhibitors with the serotonin 5-HT2c receptor | journal = Psychopharmacology | volume = 126 | issue = 3 | pages = 234–240 | date = August 1996 | pmid = 8876023 | doi = 10.1007/bf02246453 | s2cid = 24889381 }}</ref>

|-

| [[5-HT2C receptor|5-HT_2C]] || 122 || Rat || <ref name="pmid8876023" />

|-

| [[5-HT6 receptor|5-HT₆]] || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}}

|-

| [[5-HT7 receptor|5-HT₇]] || 50 || Guinea pig || <ref name="pmid10997731">{{cite journal | vauthors = Lucchelli A, Santagostino-Barbone MG, D'Agostino G, Masoero E, Tonini M | title = The interaction of antidepressant drugs with enteric 5-HT7 receptors | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 362 | issue = 3 | pages = 284–289 | date = September 2000 | pmid = 10997731 | doi = 10.1007/s002100000295 | s2cid = 24189673 }}</ref>

|-

| [[Alpha-1 adrenergic receptor|α₁]] || 90 || Human || <ref name="pmid6086881">{{cite journal | vauthors = Richelson E, Nelson A | title = Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 230 | issue = 1 | pages = 94–102 | date = July 1984 | pmid = 6086881 }}</ref>

|-

| [[Alpha-2 adrenergic receptor|α₂]] || 9,400 || Human || <ref name="pmid6086881" />

|-

| [[Dopamine receptor D1|D₁]] || 402 || Human || <ref name="pmid19091563">{{cite journal | vauthors = von Coburg Y, Kottke T, Weizel L, Ligneau X, Stark H | title = Potential utility of histamine H3 receptor antagonist pharmacophore in antipsychotics | journal = Bioorganic & Medicinal Chemistry Letters | volume = 19 | issue = 2 | pages = 538–542 | date = January 2009 | pmid = 19091563 | doi = 10.1016/j.bmcl.2008.09.012 }}</ref>

|-

| [[Dopamine receptor D2|D₂]] || 350–665 || Human || <ref name="pmid19091563" /><ref name="pmid6086881" />

|-

| [[Dopamine receptor D3|D₃]] || 504 || Human || <ref name="pmid19091563" />

|-

| [[Dopamine receptor D4|D₄]] || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}}

|-

| [[Dopamine receptor D5|D₅]] || 429 || Human || <ref name="pmid19091563" />

|-

| [[Histamine H1 receptor|H₁]] || 0.79–2.0 || Human || <ref name="pmid22033803">{{cite journal | vauthors = Appl H, Holzammer T, Dove S, Haen E, Strasser A, Seifert R | title = Interactions of recombinant human histamine H₁R, H₂R, H₃R, and H₄R receptors with 34 antidepressants and antipsychotics | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 385 | issue = 2 | pages = 145–170 | date = February 2012 | pmid = 22033803 | doi = 10.1007/s00210-011-0704-0 | s2cid = 14274150 }}</ref><ref name="pmid19091563" /><ref name="pmid6146381">{{cite journal | vauthors = Kanba S, Richelson E | title = Histamine H1 receptors in human brain labelled with [3H]doxepin | journal = Brain Research | volume = 304 | issue = 1 | pages = 1–7 | date = June 1984 | pmid = 6146381 | doi = 10.1016/0006-8993(84)90856-4 | s2cid = 45303586 }}</ref><ref name="pmid6086881" />

|-

| [[Histamine H2 receptor|H₂]] || 776 || Human || <ref name="pmid22033803" />

|-

| [[Histamine H3 receptor|H₃]] || 66,100 || Human || <ref name="pmid19091563" />

|-

| [[Histamine H4 receptor|H₄]] || 85,100 || Human || <ref name="pmid22033803" />

|-

| {{abbrlink|mACh|Muscarinic acetylcholine receptor}} || 570 || Human || <ref name="pmid6297650">{{cite journal | vauthors = El-Fakahany E, Richelson E | title = Antagonism by antidepressants of muscarinic acetylcholine receptors of human brain | journal = British Journal of Pharmacology | volume = 78 | issue = 1 | pages = 97–102 | date = January 1983 | pmid = 6297650 | pmc = 2044798 | doi = 10.1111/j.1476-5381.1983.tb17361.x }}</ref><ref name="pmid6086881" />

|- class="sortbottom"

| colspan="5" style="width: 1px;" | Values are K_i (nM). The smaller the value, the more strongly the drug binds to the site.

|}

{{See also|Pharmacology of antidepressants|Tricyclic antidepressant#Binding profiles}}

Maprotiline exhibits strong effects as a [[norepinephrine reuptake inhibitor]] with only weak actions the reuptake of [[serotonin]] and [[dopamine]].<ref>{{cite journal | vauthors = Peng WH, Lo KL, Lee YH, Hung TH, Lin YC | title = Berberine produces antidepressant-like effects in the forced swim test and in the tail suspension test in mice | journal = Life Sciences | volume = 81 | issue = 11 | pages = 933–938 | date = August 2007 | pmid = 17804020 | doi = 10.1016/j.lfs.2007.08.003 }}</ref><ref name=DrugDex>{{cite web|title=DRUGDEX Evaluations - Maprotiline|url=http://www.micromedexsolutions.com/micromedex2/librarian/ND_T/evidencexpert/ND_PR/evidencexpert/CS/1BD385/ND_AppProduct/evidencexpert/DUPLICATIONSHIELDSYNC/DA7BFE/ND_PG/evidencexpert/ND_B/evidencexpert/ND_P/evidencexpert/PFActionId/evidencexpert.DisplayDrugdexDocument?docId=2586&contentSetId=31&title=Maprotiline+Hydrochloride&servicesTitle=Maprotiline+Hydrochloride|access-date=25 April 2013}}</ref> It is also a strong [[receptor antagonist|antagonist]] of the [[histamine H1 receptor|H₁ receptor]], a moderate antagonist of the [[5-HT2 receptor|5-HT₂]] and [[α1-adrenergic receptor|α₁-adrenergic receptor]]s, and a weak antagonist of the [[D2 receptor|D₂]] and [[muscarinic acetylcholine receptor]]s. Maprotiline has also more recently been identified as a potent antagonist of the [[5-HT7 receptor|5-HT₇ receptor]], with this action potentially playing an important role in its antidepressant effectiveness.<ref name="pmid21424680">{{cite journal | vauthors = Matthys A, Haegeman G, Van Craenenbroeck K, Vanhoenacker P | title = Role of the 5-HT7 receptor in the central nervous system: from current status to future perspectives | journal = Molecular Neurobiology | volume = 43 | issue = 3 | pages = 228–253 | date = June 2011 | pmid = 21424680 | doi = 10.1007/s12035-011-8175-3 | s2cid = 25515856 }}</ref> The drug is a strong [[antihistamine]], but unlike most TCAs, has minimal [[anticholinergic]] effects.<ref name="SchatzbergNemeroff2009">{{cite book| vauthors = Nelson JC | chapter = Tricyclic and Tetracyclic Drugs | veditors = Schatzberg AF, Nemeroff CB |title=The American Psychiatric Publishing Textbook of Psychopharmacology| chapter-url = https://books.google.com/books?id=Xx7iNGdV25IC&pg=PA277|year=2009|publisher=American Psychiatric Pub|isbn=978-1-58562-309-9 | doi = 10.1176/appi.books.9781615371624.as09 |pages=277–}}</ref>

The pharmacological profile of maprotiline explains its [[antidepressant]], [[sedative]], [[anxiolytic]], and [[sympathomimetic]] activities. In accordance to the pharmacological characteristics it is used in the treatment of depression, such as depression associated with agitation or anxiety. Additionally, it shows strong antagonism against [[reserpine]]-induced effects in animal studies, as do the other 'classical' antidepressants. Although maprotiline behaves in most regards as a 'first-generation antidepressant' it is commonly referred to as 'second-generation antidepressant'.

The postulated mechanism of maprotiline is that it acts primarily by potentiation of central adrenergic synapses by blocking reuptake of norepinephrine at nerve endings. This pharmacological action is thought to be primarily responsible for the drug's antidepressant and anxiolytic effects. It is a strong norepinephrine reuptake inhibitor with only weak effects on serotonin and dopamine reuptake. At higher doses, however, maprotiline increases serotonergic transmission and increases the level of serotonin available.<ref name="pmid1815068">{{cite journal | vauthors = Miyake K, Fukuchi H, Kitaura T, Kimura M, Kimura Y, Nakahara T | title = Pharmacokinetics of maprotiline and its demethylated metabolite in serum and specific brain regions of rats after acute and chronic administration of maprotiline | journal = Journal of Pharmaceutical Sciences | volume = 80 | issue = 12 | pages = 1114–8 | date = December 1991 | pmid = 1815068 | doi = 10.1002/jps.2600801205 | url = }}</ref>

===Pharmacokinetics===

After oral use absorption is good. It binds to plasma proteins 80–90%. Maximal plasma concentration is reached 6&nbsp;hours after use. The mean time to peak is 12 hours. The [[terminal half-life]] of averages 51&nbsp;hours.

==Chemistry==

[[File:Maprotiline Formula V.1.svg|thumb|right|200px|An alternative structural representation of the central ring of maprotiline.]]

[[File:Maprotiline3Dan.gif|thumb|right|200px|A 3D representation of the structure of maprotiline. Notice the bridge in the central ring.]]

Maprotiline is a [[tetracyclic compound]] and is grouped with the TeCAs.<ref name="Zhou2013">{{cite book| vauthors = Zhou Y | chapter = New Generation of Antidepressants: Maprotiline |title=Drugs in Psychiatric Practice |chapter-url= https://books.google.com/books?id=6gglBQAAQBAJ&pg=PA222|date=22 October 2013|publisher=Elsevier|isbn=978-1-4831-9193-5|pages=222–}}</ref><ref name="LemkeWilliams2012">{{cite book| vauthors = Williams DA | chapter = Antidepressants | veditors = Lemke TL, Williams DA |title=Foye's Principles of Medicinal Chemistry|chapter-url= https://books.google.com/books?id=Sd6ot9ul-bUC&pg=PA591|date=24 January 2012|publisher=Lippincott Williams & Wilkins|isbn=978-1-60913-345-0|pages=591–}}</ref> Its [[chemical name]] is ''N''-methyl-9,10-ethanoanthracen-9(10''H'')-propylamine.<ref name="VardanyanHruby2006">{{cite book| vauthors = Vardanyan R, Hruby V | chapter = Antidepressants |title=Synthesis of Essential Drugs| chapter-url=https://books.google.com/books?id=Jjc7KYWZdOYC&pg=PA110|date=10 March 2006|publisher=Elsevier|isbn=978-0-08-046212-7|pages=110–}}</ref> The drug has a dibenzobicyclo[2.2.2]octadiene (9,10-dihydro-9,10-ethanoanthracene) [[ring system (chemistry)|ring system]]; that is, a [[tricyclic]] [[anthracene]] ring system with an [[ethylene]] [[bridged compounds|bridge]] across the central [[ring (chemistry)|ring]].<ref name="Zhou2013" /><ref name="LemkeWilliams2012" /> This results in it having a unique three-dimensional central ring (a bicyclo[2.2.2]octane or 1,4-endoethylenecyclohexane ring) and being a tetracyclic rather than a tricyclic compound.<ref name="Zhou2013" /> However, it could also or alternatively be considered to be a tricyclic and hence a TCA.<ref name="LemkeWilliams2012" /> In addition to its [[heterocyclic compound|heterocyclic]] ring system, maprotiline has an [[alkyl group|alkyl]][[amine]] [[side chain]] attached similarly to other TCAs (but notably unlike other TeCAs).<ref name="Zhou2013" /><ref name="LemkeWilliams2012" /> In terms of the side chain, it is a [[secondary amine]],<ref name="LemkeWilliams2012" /> and its [[chemical structure]], aside from the ethylene link in the central ring, is similar to that of secondary amine TCAs like [[nortriptyline]] and [[protriptyline]].<ref name="Zhou2013" /><ref name="VardanyanHruby2006" /> In accordance, the pharmacology of maprotiline is very similar to that of secondary amine TCAs.<ref name="Zhou2013" /><ref name="LemkeWilliams2012" />

Maprotiline is very similar in structure to the [[anxiolytic]], [[sedative]], and [[muscle relaxant]] drug [[benzoctamine]] (Tacitin).<ref name="Zhou2013" /><ref name="LednicerMitscher1980" /> The only structural difference between the two compounds is in the length of their side chain.<ref name="Zhou2013" /><ref name="LednicerMitscher1980">{{cite book| vauthors = Dawson AH | veditors = Lednicer D, Mitscher LA | chapter = Polycyclic Aromatic Compounds |title=The Organic Chemistry of Drug Synthesis| chapter-url = https://books.google.com/books?id=r-eqWrMoO18C&pg=PA220 |date=13 May 1980|publisher=John Wiley & Sons|isbn=978-0-471-04392-8|pages=220–}}</ref> However, this modification results in considerable differences in their pharmacological and therapeutic effects.<ref name="Zhou2013" /><ref name="LednicerMitscher1980" />

==History==

Maprotiline was developed by [[Ciba-Geigy|Ciba]] (now operated by [[Novartis]]).<ref name="pmid19557250">{{cite journal | vauthors = Andersen J, Kristensen AS, Bang-Andersen B, Strømgaard K | title = Recent advances in the understanding of the interaction of antidepressant drugs with serotonin and norepinephrine transporters | journal = Chemical Communications | issue = 25 | pages = 3677–3692 | date = July 2009 | pmid = 19557250 | doi = 10.1039/b903035m }}</ref> It was patented in 1966 and was first described in the literature in 1969.<ref name="pmid19557250" /> The drug was introduced for medical use in 1974.<ref name="pmid19557250" /><ref name="Dart2004">{{cite book| vauthors = Dart RC | chapter = Chapter 134: Cyclic Antidepressant Drugs |title=Medical Toxicology| chapter-url = https://books.google.com/books?id=BfdighlyGiwC&pg=PA836|year=2004|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-2845-4|pages=836–}}</ref> [[Generic drug|Generics]] are now widely available. It was introduced after most of the other TCAs but was the first TeCA to be developed and marketed, with the TeCAs [[mianserin]] and [[amoxapine]] following shortly thereafter and [[mirtazapine]] being introduced later on.<ref name="pmid19557250" /><ref name="Dart2004" />

==Society and culture==

[[File:Ludiomil25mg.jpg|thumb|right|200px|Ludiomil (maprotiline) 25 mg tablets by Ciba-Geigy.]]

===Generic names===

''Maprotiline'' is the [[English language|English]] and [[French language|French]] [[generic term|generic name]] of the drug and its {{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|USAN|United States Adopted Name}}, {{abbrlink|BAN|British Approved Name}}, and {{abbrlink|DCF|Dénomination Commune Française}}, while ''maprotiline hydrochloride'' is its {{abbrlink|USAN|United States Adopted Name}}, {{abbrlink|USP|United States Pharmacopeia}}, {{abbrlink|BANM|British Approved Name}} and {{abbrlink|JAN|Japanese Accepted Name}}.<ref name="Elks2014">{{cite book| vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA752|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=752–}}</ref><ref name="IndexNominum2000">{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA630|year=2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=630–}}</ref><ref name="MortonHall1999">{{cite book| vauthors = Morton IK, Hall JM |title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms|url=https://books.google.com/books?id=mqaOMOtk61IC&pg=PA171|date=31 October 1999|publisher=Springer Science & Business Media|isbn=978-0-7514-0499-9|pages=171–}}</ref><ref name="Drugs.com">{{cite web|url=https://www.drugs.com/international/maprotiline.html|title=Maprotiline - Drugs.com|website=drugs.com|access-date=28 March 2018}}</ref> Its generic name in [[Spanish language|Spanish]] and [[Italian language|Italian]] and its {{abbrlink|DCIT|Denominazione Comune Italiana}} are ''maprotilina'', in [[German language|German]] is ''maprotilin'', and in [[Latin language|Latin]] is ''maprotilinum''.<ref name="IndexNominum2000" /><ref name="Drugs.com" /> The [[methanesulfonate]] (mesylate) [[salt (chemistry)|salt]] is known unofficially as ''maprotiline methanesulfonate''.<ref name="IndexNominum2000" /><ref name="Drugs.com" />

===Brand names===

Maprotiline is marketed throughout the world, mainly under the brand name Ludiomil.<ref name="IndexNominum2000" /><ref name="Drugs.com" /> It is also available under a variety of other brand names including Deprilept, Maprolu, and Psymion among others.<ref name="IndexNominum2000" /><ref name="Drugs.com" />

{{Clear}}Although it remains available across the world, it was discontinued in the [[United Kingdom]] in July 2006. Mylan, a key manufacturer of maprotiline in the [[United States of America|United States]], discontinued production in June 2021.<ref>{{cite web | vauthors = Jensen L |title=Drug Shortage Detail: Maprotiline Tablets |url=https://www.ashp.org/drug-shortages/current-shortages/drug-shortage-detail.aspx?id=677&loginreturnUrl=SSOCheckOnly |website=www.ashp.org |publisher=American Society of Health-System Pharmacists |access-date=22 October 2023}}</ref>

== References ==

{{Reflist}}

{{Antidepressants}}

{{Navboxes

| title = [[Pharmacodynamics]]

| titlestyle = background:#ccccff

| list1 =

{{Adrenergic receptor modulators}}

{{Histamine receptor modulators}}

{{Monoamine reuptake inhibitors}}

{{Muscarinic acetylcholine receptor modulators}}

{{Serotonin receptor modulators}}

}}

{{Tricyclics}}

[[Category:Alpha-1 blockers]]

[[Category:Anthracenes]]

[[Category:Drugs developed by Novartis]]

[[Category:Antihistamines]]

[[Category:H1 receptor antagonists]]

[[Category:Muscarinic antagonists]]

[[Category:Norepinephrine reuptake inhibitors]]

[[Category:Secondary amines]]

[[Category:Serotonin receptor antagonists]]

[[Category:Tetracyclic antidepressants]]

[[Category:Tricyclic antidepressants]]