Imipramine

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Imipramine
Imipramine.svg
Imipramine-3D-balls.png
Clinical data
Trade names Tofranil, Tofranil-PM, others
Other namesMelipramine; G-22355
AHFS/Drugs.com Monograph
MedlinePlus a682389
License data
Pregnancy
category
Routes of
administration 		By mouth, intramuscular injection
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 94–96% [3]
Protein binding 86% [4]
Metabolism Liver (CYP1A2, CYP2C19, CYP2D6) [4]
Metabolites Desipramine [4]
Elimination half-life 20 hours [4]
Excretion Kidney (80%), fecal (20%) [4]
Identifiers
  • 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N,N-dimethylpropan-1-amine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard 100.000.039 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C19H24N2
Molar mass 280.415 g·mol−1
3D model (JSmol)
  • CN(C)CCCN1c2ccccc2CCc2ccccc21
  • InChI=1S/C19H24N2/c1-20(2)14-7-15-21-18-10-5-3-8-16(18)12-13-17-9-4-6-11-19(17)21/h3-6,8-11H,7,12-15H2,1-2H3 Yes check.svgY
  • Key:BCGWQEUPMDMJNV-UHFFFAOYSA-N Yes check.svgY
   (verify)

Imipramine, sold under the brand name Tofranil, among others, is a tricyclic antidepressant (TCA) mainly used in the treatment of depression. It is also effective in treating anxiety and panic disorder. Imipramine is taken by mouth.

Contents

Common side effects of imipramine include dry mouth, drowsiness, dizziness, low blood pressure, rapid heart rate, urinary retention, and electrocardiogram changes. Overdose of the medication can result in death. Imipramine appears to work by increasing levels of serotonin and norepinephrine and by blocking certain serotonin, adrenergic, histamine, and cholinergic receptors.

Imipramine was discovered in 1951 and was introduced for medical use in 1957. It was the first TCA to be marketed. Imipramine and TCAs other than amitriptyline (which, at least in the U.K., is prescribed comparatively as frequently as SSRIs) have decreased in prescription frequency with the rise of SSRIs—which have fewer inherent side effects and are far safer in overdose.[ citation needed ] Regardless of its caveats, imipramine retains importance in psychopharmacology and pediatrics (e.g., with childhood enuresis). [5] [6]

Medical uses

Imipramine is primarily used for the treatment of depression and certain anxiety disorders, including acute post-traumatic stress reactions. A significant amount of research regarding its efficacy on acute post-traumatic stress in children and adolescents has focused on trauma resulting from burn-injuries. [7] [8] [9] Although evidence for its efficacy in the treatment of chronic post-traumatic stress disorder appears to be less robust, [10] it remains a viable treatment. [11] Here, it may act fairly similarly to monoamine oxidase inhibitor phenelzine.

Caution is needed in prescribing imipramine (and its commercially-available metabolite, desipramine) in children and youth/adolescents (whether they suffer with, e.g., bed-wetting, recurrent panic attacks, acute trauma or, in the case of desipramine, [12] [13] ADHD), owing to possibility of certain side-effects which may be of particular concern in those under a certain age. [14] [15]

In the treatment of depression, it has demonstrated similar efficacy to the MAOI moclobemide. [16] It has also been used to treat nocturnal enuresis because of its ability to shorten the time of delta wave stage sleep, where wetting occurs. In veterinary medicine, imipramine is used with xylazine to induce pharmacologic ejaculation in stallions. It is also used for separation anxiety in dogs and cats. Blood levels between 150 and 250 ng/mL of imipramine plus its metabolite desipramine generally correspond to antidepressant efficacy. [17]

Contraindications

Combining it with alcohol consumption may cause more drowsiness, necessitating greater caution when drinking. [18] It may be unsafe during pregnancy. [1]

Many MAOIs are known to have serious interactions with imipramine. It is often contraindicated during their use or in the two weeks following their discontinuation. This category includes medications such as isocarboxazid, linezolid, methylene blue, phenelzine, selegiline, moclobemide, procarbazine, rasagiline, safinamide, and tranylcypromine. [18] [19]

Side effects

These side effects can be contributed to the multiple receptors that imipramine targets such as serotonin, norepinephrine, dopamine, acetylcholine, epinephrine, histamine. Those listed in italics below denote common side effects, separated by the organ systems that are affected. [20] Some side effects may be beneficial in some cases, e.g. reduction of hyperactive gag reflex; reduced random or physical strain-linked urinary leakage.

Overdose

Interactions

Like other tricyclic antidepressants, imipramine has many medication interactions. Many MAOIs have serious interactions with this medication. Other categories of medications that may interact with imipramine include blood thinners, antihistamines, muscle relaxants, sleeping pills, thyroid medications, and tranquilizers. Some medications used for various conditions such as high blood pressure, mental illness, nausea, Parkinson's disease, asthma, colds, or allergies. [18]

Certain medications increase the risk of serotonin syndrome, including selective serotonin reuptake inhibitors (SSRIs), St. John's Wort, and drugs such as ecstasy. Other prescription drugs decrease the body's ability to eliminate imipramine. These include barbiturates, some antiarrhythmic medications, some antiepileptic drugs, and certain HIV drugs (protease inhibitors). Others may cause changes in the heart rhythm, such as QT prolongation. [19]

Alcohol and tobacco may interact with imipramine. Tobacco may decrease the medication's effectiveness. [18]

Pharmacology

Pharmacodynamics

Imipramine (and metabolite) [21] [22]
SiteIMI DSI Tooltip DesipramineSpeciesRef
SERT Tooltip Serotonin transporter1.3–1.417.6–163Human [23] [24]
NET Tooltip Norepinephrine transporter20–370.63–3.5Human [23] [24]
DAT Tooltip Dopamine transporter8,5003,190Human [23]
5-HT1A ≥5,800≥6,400Human [25] [26] [27]
5-HT2A 80–150115–350Human [25] [27]
5-HT2C 120244–748Human/rat [28] [29] [26]
5-HT3 970–3,651≥2,500Rodent [26] [30]
5-HT6 190–209NDRat [31]
5-HT7 >1,000>1,000Rat [32]
α1 3223–130Human [25] [33] [24]
α2 3,100≥1,379Human [25] [33] [24]
β >10,000≥1,700Rat [34] [35] [36]
D1 >10,0005,460Human [26] [37]
D2 620–7263,400Human [37] [26] [33]
D3 387NDHuman [26]
H1 7.6–3760–110Human [25] [33] [38]
H2 5501,550Human [38]
H3 >100,000>100,000Human [38]
H4 24,0009,550Human [38]
mACh Tooltip Muscarinic acetylcholine receptor4666–198Human [25] [33]
   M1 42110Human [39]
   M2 88540Human [39]
   M3 60210Human [39]
   M4 112160Human [39]
   M5 83143Human [39]
α3β4 410–970NDHuman [40]
σ1 332–5201,990–4,000Rodent [41] [42] [43]
σ2 327–2,100≥1,611Rat [21] [42] [43]
hERG Tooltip human Ether-à-go-go-Related Gene3,400NDHuman [44]
Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site.

Imipramine affects numerous neurotransmitter systems known to be involved in the etiology of depression, anxiety, attention-deficit hyperactivity disorder (ADHD), enuresis and numerous other mental and physical conditions. Imipramine is similar in structure to some muscle relaxants, and has a significant analgesic effect and, thus, is very useful in some pain conditions.

The mechanisms of imipramine's actions include, but are not limited to, effects on:

Bethanechol may also be able to alleviate the sexual-dysfunction symptoms which may occur in the context of tricyclic-antidepressant treatment. [51] [52] [53]

Pharmacokinetics

Imipramine has a varied absolute oral bioavailability ranging from 22% to 77%, leading to significant variability in pharmacokinetics. While the drug has rapid and complete absorption after oral administration, much of the drug is affected by first pass metabolism. Food has no effect on absorption, peak drug concentration, or time to peak drug concentration. [56]

Within the body, imipramine is converted into desipramine (desmethylimipramine) as a metabolite. [56]

Chemistry

Imipramine is a tricyclic compound, specifically a dibenzazepine, and possesses three rings fused together with a side chain attached in its chemical structure. [57] Other dibenzazepine TCAs include desipramine (N-desmethylimipramine), clomipramine (3-chloroimipramine), trimipramine (2′-methylimipramine or β-methylimipramine), and lofepramine (N-(4-chlorobenzoylmethyl)desipramine). [57] [58] Imipramine is a tertiary amine TCA, with its side chain-demethylated metabolite desipramine being a secondary amine. [59] [60] Other tertiary amine TCAs include amitriptyline, clomipramine, dosulepin (dothiepin), doxepin, and trimipramine. [61] [62] The chemical name of imipramine is 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N,N-dimethylpropan-1-amine and its free base form has a chemical formula of C19H24N2 with a molecular weight of 280.407 g/mol. [63] The drug is used commercially mostly as the hydrochloride salt; the embonate (pamoate) salt is used for intramuscular administration and the free base form is not used. [63] [64] The CAS Registry Number of the free base is 50-49-7, of the hydrochloride is 113-52-0, and of the embonate is 10075-24-8. [63] [64]

History

The parent compound of imipramine, 10,11-dihydro-5H-dibenz[b,f]azepine (dibenzazepine), was first synthesized in 1899, but no pharmacological assessment of this compound or any substituted derivatives was undertaken until the late 1940s. [65] [66] [67] Imipramine was first synthesized in 1951, as an antihistamine. [68] [69] The antipsychotic effects of chlorpromazine were discovered in 1952, [70] and imipramine was then developed and studied as an antipsychotic for use in patients with schizophrenia. [33] [71] The medication was tested in several hundred patients with psychosis, but showed little effectiveness. [72] However, imipramine was serendipitously found to possess antidepressant effects in the mid-1950s following a case report of symptom improvement in a woman with severe depression who had been treated with it. [33] [71] [73] This was followed by similar observations in other patients and further clinical research. [74] [72] Subsequently, imipramine was introduced for the treatment of depression in Europe in 1958 and in the United States in 1959. [75] Along with the discovery and introduction of the monoamine oxidase inhibitor iproniazid as an antidepressant around the same time, imipramine resulted in the establishment of monoaminergic drugs as antidepressants. [73] [74] [72]

In the late 1950s, imipramine was the first TCA to be developed (by Ciba). At the first international congress of neuropharmacology in Rome, September 1958 Dr Freyhan from the University of Pennsylvania discussed as one of the first clinicians the effects of imipramine in a group of 46 patients, most of them diagnosed as "depressive psychosis". The patients were selected for this study based on symptoms such as depressive apathy, kinetic retardation and feelings of hopelessness and despair. In 30% of all patients, he reported optimal results, and in around 20%, failure. The side effects noted were atropine-like, and most patients experienced dizziness. Imipramine was first tried for treating psychotic disorders such as schizophrenia, but proved ineffective. As an antidepressant, it did well in clinical studies and it is known to work well in even the most severe cases of depression. [76] It is not surprising, therefore, that imipramine may cause a high rate of manic and hypomanic reactions in hospitalized patients with pre-existing bipolar disorder, with one study showing that up to 25% of such patients maintained on Imipramine switched into mania or hypomania. [77] Such powerful antidepressant properties have made it favorable in the treatment of treatment-resistant depression.

Before the advent of selective serotonin reuptake inhibitors (SSRIs), its sometimes intolerable side-effect profile was considered more tolerable. Therefore, it became extensively used as a standard antidepressant and later served as a prototypical drug for the development of the later-released TCAs. Since SSRIs are superior in terms of inherent side-effect tolerability (although probably inferior in terms of actual efficacy), it has, as of the 1990s, no longer been used as commonly, but is sometimes still prescribed as a second-line treatment for treating major depression. It has also seen limited use in the treatment of migraines, ADHD, and post-concussive syndrome. Imipramine has additional indications for the treatment of panic attacks, chronic pain, and Kleine-Levin syndrome. In pediatric patients, it is relatively frequently used to treat pavor nocturnus and nocturnal enuresis.

Society and culture

Generic names

Imipramine is the English and French generic name of the drug and its INN Tooltip International Nonproprietary Name, BAN Tooltip British Approved Name, and DCF Tooltip Dénomination Commune Française, while imipramine hydrochloride is its USAN Tooltip United States Adopted Name, USP Tooltip United States Pharmacopeia, BANM Tooltip British Approved Name, and JAN Tooltip Japanese Accepted Name. [63] [64] [78] [79] Its generic name in Spanish and Italian and its DCIT Tooltip Denominazione Comune Italiana are imipramina, in German is imipramin, and in Latin is imipraminum. [64] [79] The embonate salt is known as imipramine pamoate. [64] [79]

Brand names

Imipramine is marketed throughout the world mainly under the brand name Tofranil. [64] [79] Imipramine pamoate is marketed under the brand name Tofranil-PM for intramuscular injection. [64] [79] [80]

Availability

Imipramine is available for medical use widely throughout the world, including in the United States, the United Kingdom, elsewhere in Europe, India, Brazil, South Africa, Australia, and New Zealand. [79]

Between 1998 and 2017, along with amitriptyline, imipramine was the most commonly prescribed first antidepressant for children aged 5-11 years in England. [81]

See also

References

  1. 1 2 "Imipramine Use During Pregnancy". Drugs.com. 28 August 2019. Retrieved 7 February 2020.
  2. ↑ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  3. ↑ Heck HA, Buttrill SE, Flynn NW, Dyer RL, Anbar M, Cairns T, et al. (June 1979). "Bioavailability of imipramine tablets relative to a stable isotope-labeled internal standard: increasing the power of bioavailability tests". Journal of Pharmacokinetics and Biopharmaceutics. 7 (3): 233–248. doi:10.1007/BF01060015. PMID   480146. S2CID   23232584.
  4. 1 2 3 4 5 "Product Information Tolerade (imipramine hydrochloride)". TGA eBusiness Services. PMIP Pty Ltd. 4 June 2013. Archived from the original on 10 December 2019. Retrieved 16 October 2013.
  5. ↑ Michelson LK, Marchione K (February 1991). "Behavioral, cognitive, and pharmacological treatments of panic disorder with agoraphobia: critique and synthesis". Journal of Consulting and Clinical Psychology. 59 (1): 100–14. doi:10.1037/0022-006x.59.1.100. PMID   2002125.
  6. ↑ Schwartz TL, Nihalani N, Simionescu M, Hopkins G (2005). "History repeats itself: pharmacodynamic trends in the treatment of anxiety disorders". Current Pharmaceutical Design. 11 (2): 255–63. doi:10.2174/1381612053382214. PMID   15638761.
  7. ↑ Robert R, Blakeney PE, Villarreal C, Rosenberg L, Meyer WJ (July 1999). "Imipramine treatment in pediatric burn patients with symptoms of acute stress disorder: a pilot study". Journal of the American Academy of Child and Adolescent Psychiatry. 38 (7): 873–882. doi:10.1097/00004583-199907000-00018. PMID   10405506.
  8. ↑ Tcheung WJ, Robert R, Rosenberg L, Rosenberg M, Villarreal C, Thomas C, et al. (November 2005). "Early treatment of acute stress disorder in children with major burn injury". Pediatric Critical Care Medicine. 6 (6): 676–681. doi:10.1097/01.pcc.0000165562.04157.da. PMID   16276335. S2CID   43261789.
  9. ↑ Robert R, Tcheung WJ, Rosenberg L, Rosenberg M, Mitchell C, Villarreal C, et al. (November 2008). "Treating thermally injured children suffering symptoms of acute stress with imipramine and fluoxetine: a randomized, double-blind study". Burns. 34 (7): 919–928. doi:10.1016/j.burns.2008.04.009. PMID   18675519.
  10. ↑ Weizman R, Laor N, Schujovitsky A, Wolmer L, Abramovitz-Schnaider P, Freudstein-Dan A, et al. (July 1996). "Platelet imipramine binding in patients with posttraumatic stress disorder before and after phenelzine treatment". Psychiatry Research. 63 (2–3): 143–150. doi: 10.1016/0165-1781(96)02760-6 . PMID   8878310. S2CID   11314379.
  11. ↑ Astill Wright L, Sijbrandij M, Sinnerton R, Lewis C, Roberts NP, Bisson JI (December 2019). "Pharmacological prevention and early treatment of post-traumatic stress disorder and acute stress disorder: a systematic review and meta-analysis". Translational Psychiatry. 9 (1): 334. doi:10.1038/s41398-019-0673-5. PMC   6901463 . PMID   31819037.
  12. ↑ Boaden K, Tomlinson A, Cortese S, Cipriani A (2020). "Antidepressants in Children and Adolescents: Meta-Review of Efficacy, Tolerability and Suicidality in Acute Treatment". Frontiers in Psychiatry. 11: 717. doi: 10.3389/fpsyt.2020.00717 . PMC   7493620 . PMID   32982805.
  13. ↑ Ghanizadeh A (July 2013). "A systematic review of the efficacy and safety of desipramine for treating ADHD". Current Drug Safety. 8 (3): 169–174. doi:10.2174/15748863113089990029. PMID   23914752.
  14. ↑ Rosenbaum TG, Kou M (February 2005). "Are one or two dangerous? Tricyclic antidepressant exposure in toddlers". The Journal of Emergency Medicine. 28 (2): 169–174. doi:10.1016/j.jemermed.2004.08.018. PMID   15707813.
  15. ↑ Bennett HJ (June 1982). "Imipramine and enuresis: never forget its dangers". Pediatrics. 69 (6): 831–832. doi:10.1542/peds.69.6.831. PMID   7079058. S2CID   29104331.
  16. ↑ Delini-Stula A, Mikkelsen H, Angst J (October 1995). "Therapeutic efficacy of antidepressants in agitated anxious depression--a meta-analysis of moclobemide studies". Journal of Affective Disorders. 35 (1–2): 21–30. doi:10.1016/0165-0327(95)00034-K. PMID   8557884.
  17. ↑ Orsulak PJ (September 1989). "Therapeutic monitoring of antidepressant drugs: guidelines updated". Therapeutic Drug Monitoring. 11 (5): 497–507. doi:10.1097/00007691-198909000-00002. PMID   2683251.
  18. 1 2 3 4 "Imipramine: MedlinePlus Drug Information". medlineplus.gov. Retrieved 2024-04-01.
  19. 1 2 "Imipramine Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing - WebMD". www.webmd.com. Retrieved 2024-04-01.
  20. ↑ Skidmore-Roth L, ed. (2010). Mosby's Nursing Drug Reference (23rd ed.). St. Louis, MO: Mosby Elsevier.
  21. 1 2 Roth BL, Driscol J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 7 May 2022.
  22. ↑ Roth BL, Driscol J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 7 May 2022.
  23. 1 2 3 Tatsumi M, Groshan K, Blakely RD, Richelson E (December 1997). "Pharmacological profile of antidepressants and related compounds at human monoamine transporters". European Journal of Pharmacology. 340 (2–3): 249–258. doi:10.1016/s0014-2999(97)01393-9. PMID   9537821.
  24. 1 2 3 4 Owens MJ, Morgan WN, Plott SJ, Nemeroff CB (December 1997). "Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites". The Journal of Pharmacology and Experimental Therapeutics. 283 (3): 1305–1322. doi:10.1016/S0022-3565(24)37161-7. PMID   9400006.
  25. 1 2 3 4 5 6 Cusack B, Nelson A, Richelson E (May 1994). "Binding of antidepressants to human brain receptors: focus on newer generation compounds". Psychopharmacology. 114 (4): 559–565. doi:10.1007/bf02244985. PMID   7855217. S2CID   21236268.
  26. 1 2 3 4 5 6 Toll L, Berzetei-Gurske IP, Polgar WE, Brandt SR, Adapa ID, Rodriguez L, et al. (March 1998). "Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications". NIDA Research Monograph. 178: 440–466. PMID   9686407.
  27. 1 2 Wander TJ, Nelson A, Okazaki H, Richelson E (December 1986). "Antagonism by antidepressants of serotonin S1 and S2 receptors of normal human brain in vitro". European Journal of Pharmacology. 132 (2–3): 115–121. doi:10.1016/0014-2999(86)90596-0. PMID   3816971.
  28. ↑ Roth BL, Kroeze WK (2006). "Screening the receptorome yields validated molecular targets for drug discovery". Current Pharmaceutical Design. 12 (14): 1785–1795. doi:10.2174/138161206776873680. PMID   16712488.
  29. ↑ Pälvimäki EP, Roth BL, Majasuo H, Laakso A, Kuoppamäki M, Syvälahti E, et al. (August 1996). "Interactions of selective serotonin reuptake inhibitors with the serotonin 5-HT2c receptor". Psychopharmacology. 126 (3): 234–240. doi:10.1007/bf02246453. PMID   8876023. S2CID   24889381.
  30. ↑ Schmidt AW, Hurt SD, Peroutka SJ (November 1989). "'[3H]quipazine' degradation products label 5-HT uptake sites". European Journal of Pharmacology. 171 (1): 141–143. doi: 10.1016/0014-2999(89)90439-1 . PMID   2533080.
  31. ↑ Monsma FJ, Shen Y, Ward RP, Hamblin MW, Sibley DR (March 1993). "Cloning and expression of a novel serotonin receptor with high affinity for tricyclic psychotropic drugs". Molecular Pharmacology. 43 (3): 320–327. doi:10.1016/S0026-895X(25)13616-X. PMID   7680751.
  32. ↑ Shen Y, Monsma FJ, Metcalf MA, Jose PA, Hamblin MW, Sibley DR (August 1993). "Molecular cloning and expression of a 5-hydroxytryptamine7 serotonin receptor subtype". The Journal of Biological Chemistry. 268 (24): 18200–18204. doi: 10.1016/S0021-9258(17)46830-X . PMID   8394362.
  33. 1 2 3 4 5 6 7 Richelson E, Nelson A (July 1984). "Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro". The Journal of Pharmacology and Experimental Therapeutics. 230 (1): 94–102. doi:10.1016/S0022-3565(25)21446-X. PMID   6086881.
  34. ↑ Andersen PH (August 1989). "The dopamine inhibitor GBR 12909: selectivity and molecular mechanism of action". European Journal of Pharmacology. 166 (3): 493–504. doi:10.1016/0014-2999(89)90363-4. PMID   2530094.
  35. ↑ Muth EA, Haskins JT, Moyer JA, Husbands GE, Nielsen ST, Sigg EB (December 1986). "Antidepressant biochemical profile of the novel bicyclic compound Wy-45,030, an ethyl cyclohexanol derivative". Biochemical Pharmacology. 35 (24): 4493–4497. doi:10.1016/0006-2952(86)90769-0. PMID   3790168.
  36. ↑ Sánchez C, Hyttel J (August 1999). "Comparison of the effects of antidepressants and their metabolites on reuptake of biogenic amines and on receptor binding". Cellular and Molecular Neurobiology. 19 (4): 467–489. doi:10.1023/A:1006986824213. PMC   11545528 . PMID   10379421. S2CID   19490821.
  37. 1 2 Deupree JD, Montgomery MD, Bylund DB (December 2007). "Pharmacological properties of the active metabolites of the antidepressants desipramine and citalopram". European Journal of Pharmacology. 576 (1–3): 55–60. doi:10.1016/j.ejphar.2007.08.017. PMC   2231336 . PMID   17850785.
  38. 1 2 3 4 Appl H, Holzammer T, Dove S, Haen E, Strasser A, Seifert R (February 2012). "Interactions of recombinant human histamine H₁R, H₂R, H₃R, and H₄R receptors with 34 antidepressants and antipsychotics". Naunyn-Schmiedeberg's Archives of Pharmacology. 385 (2): 145–170. doi:10.1007/s00210-011-0704-0. PMID   22033803. S2CID   14274150.
  39. 1 2 3 4 5 Stanton T, Bolden-Watson C, Cusack B, Richelson E (June 1993). "Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics". Biochemical Pharmacology. 45 (11): 2352–2354. doi:10.1016/0006-2952(93)90211-e. PMID   8100134.
  40. ↑ Arias HR, Targowska-Duda KM, Feuerbach D, Sullivan CJ, Maciejewski R, Jozwiak K (March 2010). "Different interaction between tricyclic antidepressants and mecamylamine with the human alpha3beta4 nicotinic acetylcholine receptor ion channel". Neurochemistry International. 56 (4): 642–649. doi:10.1016/j.neuint.2010.01.011. PMID   20117161. S2CID   29461221.
  41. ↑ Weber E, Sonders M, Quarum M, McLean S, Pou S, Keana JF (November 1986). "1,3-Di(2-[5-3H]tolyl)guanidine: a selective ligand that labels sigma-type receptors for psychotomimetic opiates and antipsychotic drugs". Proceedings of the National Academy of Sciences of the United States of America. 83 (22): 8784–8788. Bibcode:1986PNAS...83.8784W. doi: 10.1073/pnas.83.22.8784 . PMC   387016 . PMID   2877462.
  42. 1 2 Hindmarch I, Hashimoto K (April 2010). "Cognition and depression: the effects of fluvoxamine, a sigma-1 receptor agonist, reconsidered". Human Psychopharmacology. 25 (3): 193–200. doi:10.1002/hup.1106. PMID   20373470. S2CID   26491662.
  43. 1 2 Robson MJ, Elliott M, Seminerio MJ, Matsumoto RR (April 2012). "Evaluation of sigma (σ) receptors in the antidepressant-like effects of ketamine in vitro and in vivo". European Neuropsychopharmacology. 22 (4): 308–317. doi:10.1016/j.euroneuro.2011.08.002. PMID   21911285. S2CID   24494428.
  44. ↑ Teschemacher AG, Seward EP, Hancox JC, Witchel HJ (September 1999). "Inhibition of the current of heterologously expressed HERG potassium channels by imipramine and amitriptyline". British Journal of Pharmacology. 128 (2): 479–485. doi:10.1038/sj.bjp.0702800. PMC   1571643 . PMID   10510461.
  45. ↑ Imipramine hydrochloride | DrugBank Online
  46. ↑ Smiałowski A (May 1991). "Dopamine D2 receptor blocking effect of imipramine in the rat hippocampus". Pharmacology, Biochemistry, and Behavior. 39 (1): 105–108. doi:10.1016/0091-3057(91)90404-p. PMID   1924491. S2CID   36818141.
  47. ↑ Schulze DR, Carroll FI, McMahon LR (August 2012). "Interactions between dopamine transporter and cannabinoid receptor ligands in rhesus monkeys". Psychopharmacology. 222 (3): 425–438. doi:10.1007/s00213-012-2661-9. PMC   3620032 . PMID   22374253.
  48. ↑ Dickinson KE, Matsumoto H, Anderson W, Pruitt RE, Uemura N, Hirschowitz BI (September 1988). "Muscarinic cholinergic receptor subtype on frog esophageal peptic cells: binding and secretion studies". The Journal of Pharmacology and Experimental Therapeutics. 246 (3): 879–886. doi:10.1016/S0022-3565(25)22200-5. PMID   2901489.
  49. ↑ Everett HC (November 1975). "The use of bethanechol chloride with tricyclic antidepressants". The American Journal of Psychiatry. 132 (11): 1202–1204. doi:10.1176/ajp.132.11.1202. PMID   1166898.
  50. ↑ Rosen J, Pollock BG, Altieri LP, Jonas EA (August 1993). "Treatment of nortriptyline's side effects in elderly patients: a double-blind study of bethanechol". The American Journal of Psychiatry. 150 (8): 1249–1251. doi:10.1176/ajp.150.8.1249. PMID   8101048.
  51. ↑ Yager J (April 1986). "Bethanechol chloride can reverse erectile and ejaculatory dysfunction induced by tricyclic antidepressants and mazindol: case report". The Journal of Clinical Psychiatry. 47 (4): 210–211. PMID   3957884.
  52. ↑ Segraves RT (September 1987). "Reversal by bethanechol of imipramine-induced ejaculatory dysfunction". The American Journal of Psychiatry. 144 (9): 1243–1244. doi:10.1176/ajp.144.9.1243b. PMID   3631333.
  53. ↑ Bernik M, Vieira AH, Nunes PV (December 2004). "Bethanecol chloride for treatment of clomipramine-induced orgasmic dysfunction in males". Revista do Hospital das Clinicas. 59 (6): 357–360. doi: 10.1590/s0041-87812004000600008 . PMID   15654489.
  54. ↑ Tsankova NM, Berton O, Renthal W, Kumar A, Neve RL, Nestler EJ (April 2006). "Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action". Nature Neuroscience. 9 (4): 519–525. doi:10.1038/nn1659. PMID   16501568. S2CID   21547891.
  55. ↑ Krishnan V, Nestler EJ (October 2008). "The molecular neurobiology of depression". Nature. 455 (7215): 894–902. Bibcode:2008Natur.455..894K. doi:10.1038/nature07455. PMC   2721780 . PMID   18923511.
  56. 1 2 Sallee FR, Pollock BG (May 1990). "Clinical pharmacokinetics of imipramine and desipramine". Clinical Pharmacokinetics. 18 (5): 346–364. doi:10.2165/00003088-199018050-00002. PMID   2185906.
  57. 1 2 Ritsner MS (15 February 2013). "Appendix 2: List of Psychotropic Medications". Polypharmacy in Psychiatry Practice, Volume I: Multiple Medication Use Strategies. Springer Science & Business Media. pp. 270–271. ISBN   978-94-007-5805-6.
  58. ↑ Williams DA (2008). "Antidepressants". In Lemke TL, Williams DA (eds.). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. p. 580. ISBN   978-0-7817-6879-5.
  59. ↑ Dawkins K, Manji HK, Potter TW (20 September 1994). "Dawkins Manji Potter pharmacodynamics of antidepressants". In Cutler NR, Sramek JJ, Narang PK (eds.). Pharmacodynamics and Drug Development: Perspectives in Clinical Pharmacology. John Wiley & Sons. p. 160. ISBN   978-0-471-95052-3.
  60. ↑ Baumann P, Hiemke C (23 February 2012). "Central Nervous System Drugs". In Anzenbacher P, Zanger UM (eds.). Metabolism of Drugs and Other Xenobiotics. John Wiley & Sons. pp. 302–. ISBN   978-3-527-64632-6.
  61. ↑ Anthony PK, Powers A (2002). "Drugs Used in the Therapy of Depression". In Anthony PK (ed.). Pharmacology Secrets. Elsevier Health Sciences. p. 39. ISBN   1-56053-470-2.
  62. ↑ Cowen P, Harrison P, Burns T (9 August 2012). "Drugs and other physical treatments". Shorter Oxford Textbook of Psychiatry. OUP Oxford. p. 532. ISBN   978-0-19-162675-3.
  63. 1 2 3 4 Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. p. 680. ISBN   978-1-4757-2085-3.
  64. 1 2 3 4 5 6 7 Index Nominum 2000: International Drug Directory. Taylor & Francis. 2000. p. 546. ISBN   978-3-88763-075-1.
  65. ↑ Boschmans SA, Perkin MF, Terblanche SE (1987). "Antidepressant drugs: imipramine, mianserin and trazodone". Comparative Biochemistry and Physiology. C, Comparative Pharmacology and Toxicology. 86 (2): 225–232. doi:10.1016/0742-8413(87)90073-9. PMID   2882911.
  66. ↑ Ban TA (May 2001). "Pharmacotherapy of mental illness--a historical analysis". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 25 (4): 709–727. doi:10.1016/S0278-5846(01)00160-9. PMID   11383974. S2CID   20630716.
  67. ↑ Joergensen TK, Andersen KE, Lau J, Madsen P, Huusfeldt PO (1999). "Synthesis of substituted 10,11-dihydro-5H-dibenz[b,f]azepines; key synthons in syntheses of pharmaceutically active compounds". Journal of Heterocyclic Chemistry. 36 (1): 57–64. doi:10.1002/jhet.5570360110. ISSN   0022-152X.
  68. ↑ Newbould NN (2012). "The future of drug discovery". In Walker SR (ed.). Trends and Changes in Drug Research and Development. Springer Science & Business Media. p. 109. ISBN   9789400926592.
  69. ↑ Kanba S, Wada H (22 February 1991). "Interactions with Psychotropic Drugs". In Watanabe T, Wada H (eds.). Histaminergic Neurons: Morphology and Function. CRC Press. p. 272. ISBN   978-0-8493-6425-9.
  70. ↑ Bennett MR (21 April 2014). "Monoaminergic Synapses and Schziophrenia: The Discovery of Neuroleptics". History of the Synapse. CRC Press. p. 90. ISBN   978-1-4822-8417-1.
  71. 1 2 Mitchell ES, Triggle DJ (2009). "Introduction, History, and Brain Basics". Antidepressants. Infobase Publishing. p. 15. ISBN   978-1-4381-0192-7.
  72. 1 2 3 Wilkinson ST, Ostroff RB, Katz RB, Krystal JH (2 January 2018). "Ketamine: A Promising Rapid-Acting Antidepressant". In Kim YK (ed.). Understanding Depression: Volume 2. Clinical Manifestations, Diagnosis and Treatment. Springer. p. 224. ISBN   978-981-10-6577-4.
  73. 1 2 Abdallah CG, Sanacora G, Duman RS, Krystal JH (October 2018). "The neurobiology of depression, ketamine and rapid-acting antidepressants: Is it glutamate inhibition or activation?". Pharmacology & Therapeutics. 190: 148–158. doi:10.1016/j.pharmthera.2018.05.010. PMC   6165688 . PMID   29803629.
  74. 1 2 Bernadt M (April 2007). "Drug Treatment of Depression". In Stein G, Wilkinson G (eds.). Seminars in General Adult Psychiatry. RCPsych Publications. p. 71. ISBN   978-1-904671-44-2.
  75. ↑ Lowry W (6 December 2012). "Controlled and Non-controlled but Commonly Abused Substances". Forensic Toxicology: Controlled Substances and Dangerous Drugs. Springer Science & Business Media. p. 248. ISBN   978-1-4684-3444-6.
  76. ↑ Healy D (1997). The Antidepressant Era . Harvard University Press. p.  211. ISBN   9780674039575.
  77. ↑ Bottlender R, Rudolf D, Strauss A, Möller HJ (1998). "Antidepressant-associated maniform states in acute treatment of patients with bipolar-I depression". European Archives of Psychiatry and Clinical Neuroscience. 248 (6): 296–300. doi:10.1007/s004060050053. PMID   9928908. S2CID   25542287.
  78. ↑ Morton IK, Hall JM (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. p. 151. ISBN   978-94-011-4439-1.
  79. 1 2 3 4 5 6 "Imipramine Uses, Side Effects & Warnings". Drugs.com.
  80. ↑ Pies RW (2 April 2007). Handbook of Essential Psychopharmacology. American Psychiatric Publishing. p. 79. ISBN   978-1-58562-660-1.
  81. ↑ Jack RH, Hollis C, Coupland C, Morriss R, Knaggs RD, Butler D, et al. (July 2020). Hellner C (ed.). "Incidence and prevalence of primary care antidepressant prescribing in children and young people in England, 1998-2017: A population-based cohort study". PLOS Medicine. 17 (7): e1003215. doi: 10.1371/journal.pmed.1003215 . PMC   7375537 . PMID   32697803.

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