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词条 Lofepramine
释义

  1. Medical uses

  2. Contraindications

     Pregnancy and lactation 

  3. Side effects

     Withdrawal 

  4. Overdose

  5. Interactions

  6. Pharmacology

     Pharmacodynamics  Pharmacokinetics 

  7. Chemistry

  8. History

  9. Society and culture

     Generic names  Brand names  Availability 

  10. Research

     Fatigue 

  11. References

{{Drugbox
| Verifiedfields = changed
| verifiedrevid = 462093258
| IUPAC_name = N-(4-chlorobenzoylmethyl)-3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N-methylpropan-1-amine
| image = Lofepramin.svg
| width = 250px
| image2 = Lofepramine-from-xtal-1987-ball-and-stick.png
| width2 = 250px
| tradename = Gamanil, Lomont, Tymelyt, others
| Drugs.com = {{drugs.com|international|lofepramine}}
| pregnancy_category =
| legal_UK = POM
| routes_of_administration = Oral
| bioavailability = 7%[1]
| protein_bound = 99%[2]
| metabolism = Hepatic (via cytochrome P450, including CYP2D6)[3]
| metabolites = Desipramine (major)
| elimination_half-life = Up to 5 hours;[4] 12–24 hours (active metabolites)
| excretion = Urine, feces (mostly as metabolites)
| IUPHAR_ligand = 7551
| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number = 23047-25-8
| CAS_supplemental =
26786-32-3 (hydrochloride)
| ATC_prefix = N06
| ATC_suffix = AA07
| PubChem = 3947
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 3810
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = OCA4JT7PAW
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D08140
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 47782
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 87708
| synonyms = Lopramine; DB-2182; Leo-460; WHR-2908A[4][6][7][8]
| C=26 | H=27 | Cl=1 | N=2 | O=1
| molecular_weight = 418.958 g/mol
| SMILES = Clc1ccc(cc1)C(=O)CN(C)CCCN4c2ccccc2CCc3c4cccc3
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C26H27ClN2O/c1-28(19-26(30)22-13-15-23(27)16-14-22)17-6-18-29-24-9-4-2-7-20(24)11-12-21-8-3-5-10-25(21)29/h2-5,7-10,13-16H,6,11-12,17-19H2,1H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = SAPNXPWPAUFAJU-UHFFFAOYSA-N
}}Lofepramine, sold under the brand names Gamanil, Lomont, and Tymelyt among others, is a tricyclic antidepressant (TCA) which is used to treat depression.[3][3][4] The TCAs are so named as they share the common property of having three rings in their chemical structure. Like most TCAs lofepramine is believed to work in relieving depression by increasing concentrations of the neurotransmitters norepinephrine and serotonin in the synapse, by inhibiting their reuptake.[3] It is usually considered a third-generation TCA, as unlike the first- and second-generation TCAs it is relatively safe in overdose and has milder and less frequent side effects.[5]

Lofepramine is not available in the United States, Canada, Australia or New Zealand, although it is available in Ireland, Japan, South Africa and the United Kingdom, among other countries.[6]

Medical uses

In the United Kingdom, lofepramine is licensed for the treatment of depression which is its primary use in medicine.[2][7]

Contraindications

To be used with caution, or not at all, for people with the following conditions:[3]

  • Heart disease
  • Impaired kidney or liver function
  • Narrow angle glaucoma
  • In the immediate recovery period after myocardial infarction
  • In arrhythmias (particularly heart block)
  • Mania
  • In severe liver and/or severe renal impairment[8]

And in those being treated with amiodarone or terfenadine.[3]

Pregnancy and lactation

Lofepramine use during pregnancy is advised against unless the benefits clearly outweigh the risks.[3] This is because its safety during pregnancy has not been established and animal studies have shown some potential for harm if used during pregnancy.[3] If used during the third trimester of pregnancy it can cause insufficient breathing to meet oxygen requirements, agitation and withdrawal symptoms in the infant.[3] Likewise its use by breastfeeding women is advised against, except when the benefits clearly outweigh the risks, due to the fact it is excreted in the breast milk and may therefore adversely affect the infant.[3] Although the amount secreted in breast milk is likely too small to be harmful.[24]

Side effects

The most common adverse effects (occurring in at least 1% of those taking the drug) include agitation, anxiety, confusion, dizziness, irritability, abnormal sensations, like pins and needles, without a physical cause, sleep disturbances (e.g. sleeplessness) and a drop in blood pressure upon standing up.[9] Less frequent side effects include movement disorders (like tremors), precipitation of angle closure glaucoma and the potentially fatal side effects paralytic ileus and neuroleptic malignant syndrome.[9]

Side effects with unknown frequency include (but are not limited to):[9]

  • Digestive effects:
    • Constipation
    • Diarrhoea
    • Dry mouth
    • Nausea
    • Taste disturbances
    • Vomiting
  • Effects on the heart:
    • Arrhythmia
    • ECG changes
    • Abnormal heart rhythm
    • Heart block
    • Sudden cardiac death
    • High heart rate
  • Blood abnormalities:
    • Abnormal blood cell counts
    • Blood sugar changes
    • Low blood sodium levels
  • Breast effects:
    • Breast enlargement, including in males.
    • Spontaneous breast milk secretion that is unrelated to breastfeeding or pregnancy
  • Effects on the skin:
    • Abnormal sweating
    • Hair loss
    • Hives
    • Increased light sensitivity
    • Itching
    • Rash
  • Mental / neurologic effects:
    • Delusions
    • Hallucinations
    • Headache
    • Hypomania/mania
    • Seizures
    • Suicidal behaviour
  • Other effects:
    • Appetite changes
    • Blurred vision
    • Difficulty emptying the bladder
    • Difficulty talking due to difficulties in moving the required muscles
    • Liver problems
    • Ringing in the ears
    • Sexual dysfunction, such as impotence
    • Swelling
    • Weight changes

Withdrawal

If abruptly stopped after regular use it can cause withdrawal effects such as sleeplessness, irritability and excessive sweating.[3]

Overdose

{{Main|Tricyclic antidepressant overdose}}

Compared to other TCAs, lofepramine is considered to be less toxic in overdose.[9] Its treatment is mostly a matter of trying to reduce absorption of the drug, if possible, using gastric lavage and monitoring for adverse effects on the heart.[3]

Interactions

Lofepramine is known to interact with:[9][3]

  • Alcohol. Increased sedative effect.
  • Altretamine. Risk of severe drop in blood pressure upon standing.
  • Analgesics (painkillers). Increased risk of ventricular arrhythmias.
  • Anticoagulants (blood thinners). Lofepramine may inhibit the metabolism of certain anticoagulants leading to a potentially increased risk of bleeding.
  • Anticonvulsants. Possibly reduce the anticonvulsant effect of antiepileptics by lowering the seizure threshold.
  • Antihistamines. Possible increase of antimuscarinic (potentially increasing risk of paralytic ileus, among other effects) and sedative effects.
  • Antimuscarinics. Possible increase of antimuscarinic side-effects.
  • Anxiolytics and hypnotics. Increased sedative effect.
  • Apraclonidine. Avoidance advised by manufacturer of apraclonidine.
  • Brimonidine. Avoidance advised by manufacturer of brimonidine.
  • Clonidine. Lofepramine may reduce the antihypertensive effects of clonidine.
  • Diazoxide. Enhanced hypotensive (blood pressure-lowering) effect.
  • Digoxin. May increase risk of irregular heart rate.
  • Disulfiram. May require a reduction of lofepramine dose.
  • Diuretics. Increased risk of reduced blood pressure on standing.
  • Cimetidine, diltiazem, verapamil. May increase concentration of lofepramine in the blood plasma.
  • Hydralazine. Enhanced hypotensive effect.
  • Monoamine oxidase inhibitors (MAOIs). Advised not to be started until at least 2 weeks after stopping MAOIs. MAOIs are advised not to be started until at least 1–2 weeks after stopping TCAs like lofepramine.
  • Moclobemide. Moclobemide is advised not to be started until at least one week after treatment with TCAs is discontinued.
  • Nitrates. Could possibly reduce the effects of sublingual tablets of nitrates (failure to dissolve under tongue owing to dry mouth).
  • Rifampicin. May accelerate lofepramine metabolism thereby decreasing plasma concentrations of lofepramine.
  • Ritonavir. May increase lofepramine concentration in the blood plasma.
  • Sodium nitroprusside. Enhanced hypotensive effect.
  • Thyroid hormones. Effects on the heart of lofepramine may be exacerbated.

Pharmacology

Pharmacodynamics

{{See also|Pharmacology of antidepressants|Tricyclic antidepressant#Binding profiles}}
Lofepramine (and metabolite)[10]
Site LPA|LofepramineDSI|Desipramine Species Ref
{{abbrlink>SERT|Serotonin transporter}} 70 17.6–163 Human [11][12]
{{abbrlink>NET|Norepinephrine transporter}} 5.4 0.63–3.5 Human [11][12]
DAT|Dopamine transporter}} >10,000 3,190 Human [11]
5-HT1A 4,600 ≥6,400 Human [39][13]
5-HT2A 200 115–350 Human [39][13]
5-HT2C ND|No data}} 244–748 Rat [14][15]
5-HT3 ND|No data}} 4,402 Mouse [15]
5-HT7 ND|No data}} >1,000 Rat [16]
α1 100 23–130 Human [39][48][12]
α2 2,700 ≥1,379 Human [39][48][12]
β >10,000 ≥1,700 Rat [17][18]
D1 500 5,460 Human/rat [19]
D2 2,000 3,400 Human [39][48]
H1 245–360 60–110 Human [20][21][22]
H2 4,270 1,550 Human [20]
H3 79,400 >100,000 Human [20]
H4 36,300 9,550 Human [20]
{{abbrlink>mACh|Muscarinic acetylcholine receptor}} 67 66–198 Human [21][22]
  M1 67 110 Human [23]
  M2 330 540 Human [23]
  M3 130 210 Human [23]
  M4 340 160 Human [23]
  M5 460 143 Human [23]
σ1 2,520 4,000 Rodent [24][10]
σ2 ND|No data}} 1,611 Rat [10]
Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site.

Lofepramine is a strong inhibitor of norepinephrine reuptake and a moderate inhibitor of serotonin reuptake.[10] It is a weak-intermediate level antagonist of the muscarinic acetylcholine receptors.[10]

Lofepramine has been said to be a prodrug of desipramine,[25] although there is also evidence against this notion.[4]

Pharmacokinetics

Lofepramine is extensively metabolized, via cleavage of the p-chlorophenacyl group, to the TCA, desipramine, in humans.[26][4][6] However, it is unlikely this property plays a substantial role in its overall effects as lofepramine exhibits lower toxicity and anticholinergic side effects relative to desipramine while retaining equivalent antidepressant efficacy.[4] The p-chlorophenacyl group is metabolized to p-chlorobenzoic acid which is then conjugated with glycine and excreted in the urine.[26] The desipramine metabolite is partly secreted in the faeces.[26] Other routes of metabolism include hydroxylation, glucuronidation, N-dealkylation and N-oxidation.[26][6]

Chemistry

Lofepramine is a tricyclic compound, specifically a dibenzazepine, and possesses three rings fused together with a side chain attached in its chemical structure.[27] Other dibenzazepine TCAs include imipramine, desipramine, clomipramine, and trimipramine.[27][28] Lofepramine is a tertiary amine TCA, with its side chain-demethylated metabolite desipramine being a secondary amine.[29][25] Unlike other tertiary amine TCAs, lofepramine has a bulky 4-chlorobenzoylmethyl substituent on its amine instead of a methyl group.[28] Although lofepramine is technically a tertiary amine, it acts in large part as a prodrug of desipramine, and is more similar to secondary amine TCAs in its effects.[92] Other secondary amine TCAs besides desipramine include nortriptyline and protriptyline.[30][31] The chemical name of lofepramine is N-(4-chlorobenzoylmethyl)-3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N-methylpropan-1-amine and its free base form has a chemical formula of C26H27ClN2O with a molecular weight of 418.958 g/mol.[6] The drug is used commercially mostly as the hydrochloride salt; the free base form is not used.[6][3] The CAS Registry Number of the free base is 23047-25-8 and of the hydrochloride is 26786-32-3.[6][3]

History

Lofepramine was developed by Leo Läkemedel AB.[32] It first appeared in the literature in 1969 and was patented in 1970.[32] The drug was first introduced for the treatment of depression in either 1980 or 1983.[32][33]

Society and culture

Generic names

Lofepramine is the generic name of the drug and its {{abbrlink|INN|International Nonproprietary Name}} and {{abbrlink|BAN|British Approved Name}}, while lofepramine hydrochloride is its {{abbrlink|USAN|United States Adopted Name}}, {{abbrlink|BANM|British Approved Name}}, and {{abbrlink|JAN|Japanese Accepted Name}}.[34][3][35][36] Its generic name in French and its {{abbrlink|DCF|Dénomination Commune Française}} are lofépramine, in Spanish and Italian and its {{abbrlink|DCIT|Denominazione Comune Italiana}} are lofepramina, in German is lofepramin, and in Latin is lofepraminum.[3][36]

Brand names

Brand names of lofepramine include Amplit, Deftan, Deprimil, Emdalen, Gamanil, Gamonil, Lomont, Tymelet, and Tymelyt.[6][34][3][36]

Availability

In the United Kingdom, lofepramine is marketed (as the hydrochloride salt) in the form of 70 mg tablets [8] and 70 mg/5 mL oral suspension.[37]

Research

Fatigue

A formulation containing lofepramine and the amino acid phenylalanine is under investigation as a treatment for fatigue as of 2015.[38]

References

1. ^{{cite journal|title=Lofepramine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness|date=February 1989|volume=37|issue=2|pages=123–140|pmid=2649353|doi=10.2165/00003495-198937020-00003|author1=Lancaster, SG |author2=Gonzalez, JP |journal=Drugs}}
2. ^1 {{cite web|title=Lofepramine 70mg tablets - Summary of Product Characteristics (SPC)|work=electronic Medicines Compendium|publisher=Merck Serono|date=18 November 2010|accessdate=21 November 2013|url=http://www.medicines.org.uk/emc/medicine/20961/SPC/Lofepramine+70mg+tablets/}}
3. ^1 2 3 4 5 6 {{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA614|year=2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=614–}}
4. ^1 2 3 {{cite journal | author = Leonard BE | title = A comparison of the pharmacological properties of the novel tricyclic antidepressant lofepramine with its major metabolite, desipramine: a review | journal = International Clinical Psychopharmacology | volume = 2 | issue = 4 | pages = 281–97 |date=October 1987 | pmid = 2891742 | doi = 10.1097/00004850-198710000-00001| url = }}
5. ^{{cite web|url=http://www.safcglobal.com/safc-pharma/en-us/home/small-molecule-api/services-overview/generic-products/lofepramine-hydrochloride.html |title=SAFC Commercial Life Science Products & Services | Sigma-Aldrich |publisher=Safcglobal.com |date=2015-05-12 |accessdate=2016-02-24}}
6. ^1 2 3 4 5 {{cite web|title=Lofepramine Hydrochloride: Martindale: The Complete Drug Reference|url=https://www.medicinescomplete.com/mc/martindale/current/2522-w.htm|website=MedicinesComplete|publisher=The Pharmaceutical Press|accessdate=3 August 2017|language=en}}
7. ^{{cite book | isbn = 978-0-85711-084-8 | title = British National Formulary (BNF) | last1 = Joint Formulary Committee | year = 2013 | publisher = Pharmaceutical Press | location = London, UK | edition = 65 | pages = }}
8. ^1 {{cite web|title=Lofepramine 70mg Tablets|url=http://www.medicines.org.uk/emc/medicine/27917/spc}}
9. ^1 2 3 4 5 {{cite book|editor1-last=Joint Formulary Committee|title=BNF 73 (British National Formulary) March 2017|date=2017|publisher=Pharmaceutical Press|location=London, UK|isbn=978-0857112767|pages=354–355}}
10. ^1 2 3 4 {{cite web | title = PDSP Ki Database | work = Psychoactive Drug Screening Program (PDSP) | author1 = Roth, BL | author2 = Driscol, J | publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health | accessdate = 14 August 2017 | url = https://kidbdev.med.unc.edu/databases/pdsp.php?knowID=0&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=lofepramine&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query}}
11. ^1 2 {{cite journal | vauthors = Tatsumi M, Groshan K, Blakely RD, Richelson E | title = Pharmacological profile of antidepressants and related compounds at human monoamine transporters | journal = Eur. J. Pharmacol. | volume = 340 | issue = 2–3 | pages = 249–58 | year = 1997 | pmid = 9537821 | doi = 10.1016/s0014-2999(97)01393-9| url = }}
12. ^1 2 3 {{cite journal | vauthors = Owens MJ, Morgan WN, Plott SJ, Nemeroff CB | title = Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites | journal = J. Pharmacol. Exp. Ther. | volume = 283 | issue = 3 | pages = 1305–22 | year = 1997 | pmid = 9400006 | doi = | url = }}
13. ^1 {{cite journal | vauthors = Wander TJ, Nelson A, Okazaki H, Richelson E | title = Antagonism by antidepressants of serotonin S1 and S2 receptors of normal human brain in vitro | journal = Eur. J. Pharmacol. | volume = 132 | issue = 2–3 | pages = 115–21 | year = 1986 | pmid = 3816971 | doi = 10.1016/0014-2999(86)90596-0| url = }}
14. ^{{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 = 234–40 | year = 1996 | pmid = 8876023 | doi = 10.1007/bf02246453| url = }}
15. ^1 {{cite journal | vauthors = Toll L, Berzetei-Gurske IP, Polgar WE, Brandt SR, Adapa ID, Rodriguez L, Schwartz RW, Haggart D, O'Brien A, White A, Kennedy JM, Craymer K, Farrington L, Auh JS | title = Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications | journal = NIDA Res. Monogr. | volume = 178 | issue = | pages = 440–66 | year = 1998 | pmid = 9686407 | doi = | url = }}
16. ^{{cite journal | vauthors = Shen Y, Monsma FJ, Metcalf MA, Jose PA, Hamblin MW, Sibley DR | title = Molecular cloning and expression of a 5-hydroxytryptamine7 serotonin receptor subtype | journal = J. Biol. Chem. | volume = 268 | issue = 24 | pages = 18200–4 | year = 1993 | pmid = 8394362 | doi = | url = }}
17. ^{{cite journal | vauthors = Muth EA, Haskins JT, Moyer JA, Husbands GE, Nielsen ST, Sigg EB | title = Antidepressant biochemical profile of the novel bicyclic compound Wy-45,030, an ethyl cyclohexanol derivative | journal = Biochem. Pharmacol. | volume = 35 | issue = 24 | pages = 4493–7 | year = 1986 | pmid = 3790168 | doi = 10.1016/0006-2952(86)90769-0| url = }}
18. ^{{cite journal | vauthors = Sánchez C, Hyttel J | title = Comparison of the effects of antidepressants and their metabolites on reuptake of biogenic amines and on receptor binding | journal = Cell. Mol. Neurobiol. | volume = 19 | issue = 4 | pages = 467–89 | year = 1999 | pmid = 10379421 | doi = 10.1023/A:1006986824213| url = }}
19. ^{{cite journal | vauthors = Deupree JD, Montgomery MD, Bylund DB | title = Pharmacological properties of the active metabolites of the antidepressants desipramine and citalopram | journal = Eur. J. Pharmacol. | volume = 576 | issue = 1–3 | pages = 55–60 | year = 2007 | pmid = 17850785 | pmc = 2231336 | doi = 10.1016/j.ejphar.2007.08.017 | url = }}
20. ^1 2 3 {{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 Schmiedebergs Arch. Pharmacol. | volume = 385 | issue = 2 | pages = 145–70 | year = 2012 | pmid = 22033803 | doi = 10.1007/s00210-011-0704-0 | url = }}
21. ^1 2 3 4 5 6 {{cite journal | vauthors = Cusack B, Nelson A, Richelson E | title = Binding of antidepressants to human brain receptors: focus on newer generation compounds | journal = Psychopharmacology | volume = 114 | issue = 4 | pages = 559–65 | year = 1994 | pmid = 7855217 | doi = 10.1007/bf02244985| url = }}
22. ^1 2 3 4 {{cite journal | vauthors = Richelson E, Nelson A | title = Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro | journal = J. Pharmacol. Exp. Ther. | volume = 230 | issue = 1 | pages = 94–102 | year = 1984 | pmid = 6086881 | doi = | url = }}
23. ^1 2 3 4 {{cite journal |vauthors=Stanton T, Bolden-Watson C, Cusack B, Richelson E |title=Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics |journal=Biochem. Pharmacol. |volume=45 |issue=11 |pages=2352–4 |year=1993 |pmid=8100134 |doi= 10.1016/0006-2952(93)90211-e|url=}}
24. ^{{cite journal | vauthors = Weber E, Sonders M, Quarum M, McLean S, Pou S, Keana JF | title = 1,3-Di(2-[5-3H]tolyl)guanidine: a selective ligand that labels sigma-type receptors for psychotomimetic opiates and antipsychotic drugs | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 83 | issue = 22 | pages = 8784–8 | year = 1986 | pmid = 2877462 | pmc = 387016 | doi = 10.1073/pnas.83.22.8784| url = }}
25. ^1 {{cite book|author1=Pavel Anzenbacher|author2=Ulrich M. Zanger|title=Metabolism of Drugs and Other Xenobiotics|url=https://books.google.com/books?id=f-XHh17NfwgC&pg=PA302|date=23 February 2012|publisher=John Wiley & Sons|isbn=978-3-527-64632-6|pages=302–}}
26. ^1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 {{cite web|title=Lofepramine 70 mg Film-coated Tablets - Summary of Product Characteristics (SPC) - (eMC)|url=http://www.medicines.org.uk/emc/medicine/33411|website=electronic Medicines Compendium (eMC)|date=April 2016|accessdate=3 August 2017|publisher=Datapharm}}
27. ^1 {{cite book|author=Michael S Ritsner|title=Polypharmacy in Psychiatry Practice, Volume I: Multiple Medication Use Strategies|url=https://books.google.com/books?id=jy-LMZU7338C&pg=PA270|date=15 February 2013|publisher=Springer Science & Business Media|isbn=978-94-007-5805-6|pages=270–271}}
28. ^1 {{cite book|author1=Thomas L. Lemke|author2=David A. Williams|title=Foye's Principles of Medicinal Chemistry|url=https://books.google.com/books?id=R0W1ErpsQpkC&pg=PA580|year=2008|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-6879-5|pages=580, 607}}
29. ^{{cite book|author1=Neal R. Cutler|author2=John J. Sramek|author3=Prem K. Narang|title=Pharmacodynamics and Drug Development: Perspectives in Clinical Pharmacology|url=https://books.google.com/books?id=ncRXa8Dq88QC&pg=PA160|date=20 September 1994|publisher=John Wiley & Sons|isbn=978-0-471-95052-3|pages=160–}}
30. ^{{cite book|author=Patricia K. Anthony|title=Pharmacology Secrets|url=https://books.google.com/books?id=_QQsj3PAUrEC&pg=PA39|year=2002|publisher=Elsevier Health Sciences|isbn=1-56053-470-2|pages=39–}}
31. ^1 {{cite book|author1=Philip Cowen|author2=Paul Harrison|author3=Tom Burns|title=Shorter Oxford Textbook of Psychiatry|url=https://books.google.com/books?id=Y1DtSGq-LnoC&pg=PA532|date=9 August 2012|publisher=OUP Oxford|isbn=978-0-19-162675-3|pages=532–}}
32. ^1 2 {{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 = Chem. Commun. | volume = | issue = 25 | pages = 3677–92 | year = 2009 | pmid = 19557250 | doi = 10.1039/b903035m | url = }}
33. ^{{cite book|author=Richard C. Dart|title=Medical Toxicology|url=https://books.google.com/books?id=BfdighlyGiwC&pg=PA836|year=2004|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-2845-4|pages=836–}}
34. ^1 2 3 4 5 {{cite book|author=J. Elks|title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA738|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=738–}}
35. ^{{cite book|author1=I.K. Morton|author2=Judith M. Hall|title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms|url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA168|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-4439-1|pages=168–}}
36. ^1 2 3 https://www.drugs.com/international/lofepramine.html
37. ^{{cite web|title=Lofepramine Rosemont 70mg/5ml Oral Suspension - Summary of Product Characteristics (SPC) - (eMC)|url=http://www.medicines.org.uk/emc/medicine/10656|date=26 January 2016|accessdate=3 August 2017}}
38. ^{{cite web|title=Lofepramine/phenylalanine - MultiCell Technologies - AdisInsight|url=http://adisinsight.springer.com/drugs/800022855|website=AdisInsight|publisher=Springer International Publishing AG|accessdate=3 August 2017|language=en}}
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| title = Pharmacodynamics
| titlestyle = background:#ccccff
| list1 ={{Adrenergic receptor modulators}}{{Histamine receptor modulators}}{{Monoamine reuptake inhibitors}}{{Muscarinic acetylcholine receptor modulators}}{{Serotonin receptor modulators}}
}}{{Tricyclics}}

11 : Alpha-1 blockers|Amines|Antihistamines|Chloroarenes|Dibenzazepines|Ketones|Muscarinic antagonists|Norepinephrine reuptake inhibitors|Prodrugs|Serotonin antagonists|Tricyclic antidepressants
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