maprotiline maprotiline maprotiline, sold under the brand name ludiomil among others, is a tetracyclic antidepressant (teca) that is used in the treatment of depression. it may alternatively be classified as a tricyclic antidepressant (tca), specifically a secondary amine. in terms of its chemistry and pharmacology, maprotiline is closely related to other secondary amine tcas like nortriptyline and protriptyline, and has similar effects to them. maprotilineclinical datatrade namesludiomil, othersother namesmaprotiline hydrochloride; maprotiline methanesulfonate; ba 34276ahfs/drugs.commonographmedlineplusa682158routes ofadministrationoral, intramuscular, intravenousatc coden06aa21 (who) legal statuslegal status au: s4 (prescription only) us: ℞-only pharmacokinetic databioavailability66–70%protein binding88%metabolismhepaticonset of action6 hourselimination half-life27–58 hoursexcretionurine (57%) and bile (30%) as glucuronides, 3–4% as unchanged drugidentifiers iupac name n-methyl-9,10-ethanoanthracene-9(10h)-propanamine cas number10262-69-8 y 10347-81-6 (hydrochloride) 58902-67-3 (mesylate)pubchem cid4011iuphar/bps2402drugbankdb00934 ychemspider23719117 nunii2u1w68trofkeggd02566 ychemblchembl21731 ycomptox dashboard (epa)dtxsid7045029 echa infocard100.030.532 chemical and physical dataformulac20h23nmolar mass277.411 g·mol−13d model (jsmol)interactive image smiles cnccc12cc(c3ccccc31)c1ccccc12 inchi inchi=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+ nkey:qslmdecmdjkhmq-gsxcwmcisa-n n ny (what is this?) (verify) 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. treatment of depression of all forms and severities (endogenous, psychotic, involutional, and neurotic) especially for depression associated with agitation or anxiety panic disorder neuropathic pain treatment of the depressive phase in bipolar depression for the symptomatic relief of anxiety, 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. 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. in general, lower dosages are recommended for patients over 60 years of age. dosages of 50 mg to 75 mg daily are usually satisfactory as maintenance therapy for elderly patients who do not tolerate higher amounts. available forms coated tablets, 10 mg, 25 mg, 50 mg, and 75 mg injectable concentrate, 25 mg contraindications maprotiline may worsen psychotic conditions like schizophrenia and should be given with caution. the antipsychotic treatment should be continued. patients with bipolar affective disorder should not receive antidepressants whilst in a manic phase, as antidepressants can worsen mania. 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 tumors, alcohol withdrawal, other medications) serious cardiovascular conditions (arrhythmias, heart insufficience, state after myocardial infarction etc.) treatment of patients under age 18 suicidal patients same as 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. 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. most often seen are: dizziness drowsiness somnolence fatigue 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: impotence, priapism, delayed ejaculation, anejaculation, decreased libido sexual dysfunction in women: decreased libido, vaginal dryness, 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 seizures (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, confusion, tachycardia) with a 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 like amitriptyline. 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) are not indicative of addiction and can be avoided by reducing the daily dose of maprotiline gradually by approximately 25% each week. if treatment has to be stopped at once due to medical reasons, the use of a benzodiazepine (e.g. lorazepam, clonazepam, or alprazolam) for a maximum of 4 weeks as needed will usually suppress withdrawal symptoms. interactions maprotiline has 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: irreversible mao-inhibitors: agitation, delirium, coma, hyperpyrexia (high fever), seizures and severe changes in blood pressure. treatment-resistant and hospitalized patients may be treated concomitantly with an mao-inhibitor, if they are closely monitored and if the initial dose of the mao-inhibitor is low. increased drug actions: other antidepressants, barbiturates, narcotics, sedating antihistamines, anticonvulsive drugs, alcohol - resulting in increased central depression anticholinergics (antiparkinsonian agents, tcas and tecas) - resulting in increased anticholinergic action (dry mouth, constipation etc.) sympathomimetics (also those used in local anesthetics like noradrenaline) : sympathomimetic effects increased (increased blood pressure, pulse rate, paleness of skin etc.) nitrates and antihypertensives (e.g. beta-blockers) - increased antihypertensive action with pronounced fall in blood pressure decreased drug actions: guanethidine, reserpine, guanfacine : antihypertensive effects decreased clonidine : antihypertensive 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 anticonceptive 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 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 high incidence of maprotiline side effects. due to the long half-lives of fluoxetine and fluvoxamine this effect may persist. pharmacology pharmacodynamics maprotiline siteki (nm)speciesref sert5,800human net11–12human dat1,000human 5-ht2a51rat 5-ht2c122rat 5-ht6ndndnd 5-ht750guinea pig α190human α29,400human d1402human d2350–665human d3504human d4ndndnd d5429human h10.79–2.0human h2776human h366,100human h485,100human mach570human values are ki (nm). the smaller the value, the more strongly the drug binds to the site.