Butriptyline

Last updated
Butriptyline
Butriptyline.svg
Clinical data
Trade names Evadyne, others
Other namesAY-62014 [1]
Routes of
administration
Oral
ATC code
Legal status
Legal status
  • BR: Class C1 (Other controlled substances) [2]
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability ? [3]
Protein binding >90% [3]
Metabolism Hepatic (N-demethylation)
Metabolites Norbutriptyline [3]
Elimination half-life 20 hours [3]
Identifiers
  • (±)-3-(10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-yl)-N,N,2-trimethylpropan-1-amine
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C21H27N
Molar mass 293.454 g·mol−1
3D model (JSmol)
Chirality Racemic mixture
  • c1cc3c(cc1)CCc2c(cccc2)C3CC(C)CN(C)C
  • InChI=1S/C21H27N/c1-16(15-22(2)3)14-21-19-10-6-4-8-17(19)12-13-18-9-5-7-11-20(18)21/h4-11,16,21H,12-15H2,1-3H3 Yes check.svgY
  • Key:ALELTFCQZDXAMQ-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Butriptyline, sold under the brand name Evadyne among others, is a tricyclic antidepressant (TCA) that has been used in the United Kingdom and several other European countries for the treatment of depression but appears to no longer be marketed. [1] [4] [5] [6] [7] Along with trimipramine, iprindole, and amoxapine, it has been described as an "atypical" or "second-generation" TCA due to its relatively late introduction and atypical pharmacology. [8] [9] It was very little-used compared to other TCAs, with the number of prescriptions dispensed only in the thousands. [10]

Contents

Medical uses

Butriptyline was used in the treatment of depression. [11] It was usually used at dosages of 150–300 mg/day. [12]

Side effects

Butriptyline is closely related to amitriptyline, and produces similar effects as other TCAs, but its side effects like sedation are said to be reduced in severity and it has a lower risk of interactions with other medications. [6] [7] [10]

Butriptyline has potent antihistamine effects, resulting in sedation and somnolence. [13] It also has potent anticholinergic effects, [14] resulting in side effects like dry mouth, constipation, urinary retention, blurred vision, and cognitive/memory impairment. [13] The drug has relatively weak effects as an alpha-1 blocker and has no effects as a norepinephrine reuptake inhibitor, [15] [16] so is associated with little to no antiadrenergic and adrenergic side effects. [15] [14] [ additional citation(s) needed ]

Overdose

Pharmacology

Pharmacodynamics

Butriptyline [17]
SiteKi (nM)SpeciesRef
SERT Tooltip Serotonin transporter1,360
4,300
10,000 (IC50 Tooltip Half-maximal inhibitory concentration)
Human
Rat
Rat
[16]
[18]
[19]
NET Tooltip Norepinephrine transporter5,100
990
1,700 (IC50)
Human
Rat
Rat
[16]
[18]
[19]
DAT Tooltip Dopamine transporter3,940
2,800
5,200 (IC50)
Human
Rat
Rat
[16]
[18]
[19]
5-HT1A 7,000Human [20]
5-HT2A 380Human [20]
5-HT2C NDNDND
α1 570Human [15]
α2 4,800Human [15]
D2 NDNDND
H1 1.1Human [15]
mACh Tooltip Muscarinic acetylcholine receptor35Human [15]
Values are Ki (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site.

In vitro , butriptyline is a strong antihistamine and anticholinergic, moderate 5-HT2 and α1-adrenergic receptor antagonist, and very weak or negligible monoamine reuptake inhibitor. [15] [20] [16] [19] These actions appear to confer a profile similar to that of iprindole and trimipramine with serotonin-blocking effects as the apparent predominant mediator of mood-lifting efficacy. [21] [19] [18]

However, in small clinical trials, using similar doses, butriptyline was found to be similarly effective to amitriptyline and imipramine as an antidepressant, despite the fact that both of these TCAs are far stronger as both 5-HT2 antagonists and serotonin–norepinephrine reuptake inhibitors. [15] [20] [22] As a result, it may be that butriptyline has a different mechanism of action, or perhaps functions as a prodrug in the body to a metabolite with different pharmacodynamics.

Pharmacokinetics

Therapeutic concentrations of butriptyline are in the range of 60–280 ng/mL (204–954 nmol/L). [23] Its plasma protein binding is greater than 90%. [3]

Chemistry

Butriptyline is a tricyclic compound, specifically a dibenzocycloheptadiene, and possesses three rings fused together with a side chain attached in its chemical structure. [24] Other dibenzocycloheptadiene TCAs include amitriptyline, nortriptyline, and protriptyline. [24] Butriptyline is an analogue of amitriptyline with an isobutyl side chain instead of a propylidene side chain. [10] [25] It is a tertiary amine TCA, with its side chain-demethylated metabolite norbutriptyline being a secondary amine. [26] [27] Other tertiary amine TCAs include amitriptyline, imipramine, clomipramine, dosulepin (dothiepin), doxepin, and trimipramine. [28] [29] The chemical name of butriptyline is 3-(10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-yl)-N,N,2-trimethylpropan-1-amine and its free base form has a chemical formula of C21H27N with a molecular weight of 293.446 g/mol. [1] The drug has been used commercially both as the free base and as the hydrochloride salt. [1] [4] The CAS Registry Number of the free base is 15686-37-0 and of the hydrochloride is 5585-73-9. [1] [4]

History

Butriptyline was developed by Wyeth and introduced in the United Kingdom in either 1974 or 1975. [5] [30] [31]

Society and culture

Generic names

Butriptyline 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 butriptyline hydrochloride is its BANM Tooltip British Approved Name and USAN Tooltip United States Adopted Name. [1] [4] [11] Its generic name in Latin is butriptylinum, in German is butriptylin, and in Spanish is butriptylina. [4]

Brand names

Butriptyline has been marketed under the brand names Evadene, Evadyne, Evasidol, and Centrolese. [1] [4] [5]

Availability

Butriptyline has been marketed in Europe, including in the United Kingdom, Belgium, Luxembourg, Austria, and Italy. [4] [5]

Related Research Articles

<span class="mw-page-title-main">Tricyclic antidepressant</span> Class of medications

Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants. TCAs were discovered in the early 1950s and were marketed later in the decade. They are named after their chemical structure, which contains three rings of atoms. Tetracyclic antidepressants (TeCAs), which contain four rings of atoms, are a closely related group of antidepressant compounds.

<span class="mw-page-title-main">Tetracyclic antidepressant</span> Class of pharmaceutical drugs

Tetracyclic antidepressants (TeCAs) are a class of antidepressants that were first introduced in the 1970s. They are named after their tetracyclic chemical structure, containing four rings of atoms, and are closely related to the tricyclic antidepressants (TCAs), which contain three rings of atoms.

<span class="mw-page-title-main">Maprotiline</span> Antidepressant

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 such-other secondary-amine TCAs as nortriptyline and protriptyline and has similar effects to them, albeit with more distinct anxiolytic effects. Additionally, whereas protriptyline tends to be somewhat more stimulating and in any case is distinctly more-or-less non-sedating, mild degrees of sedation may be experienced with maprotiline.

<span class="mw-page-title-main">Amitriptyline</span> Tricyclic antidepressant

Amitriptyline, sold under the brand name Elavil among others, is a tricyclic antidepressant primarily used to treat major depressive disorder, and a variety of pain syndromes such as neuropathic pain, fibromyalgia, migraine and tension headaches. Due to the frequency and prominence of side effects, amitriptyline is generally considered a second-line therapy for these indications.

<span class="mw-page-title-main">Amoxapine</span> Tricyclic antidepressant medication

Amoxapine, sold under the brand name Asendin among others, is a tricyclic antidepressant (TCA). It is the N-demethylated metabolite of loxapine. Amoxapine first received marketing approval in the United States in 1980, approximately 10 to 20 years after most of the other TCAs were introduced in the United States.

<span class="mw-page-title-main">Imipramine</span> Antidepressant

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.

<span class="mw-page-title-main">Desipramine</span> Antidepressant

Desipramine, sold under the brand name Norpramin among others, is a tricyclic antidepressant (TCA) used in the treatment of depression. It acts as a relatively selective norepinephrine reuptake inhibitor, though it does also have other activities such as weak serotonin reuptake inhibitory, α1-blocking, antihistamine, and anticholinergic effects. The drug is not considered a first-line treatment for depression since the introduction of selective serotonin reuptake inhibitor (SSRI) antidepressants, which have fewer side effects and are safer in overdose.

<span class="mw-page-title-main">Clomipramine</span> Antidepressant

Clomipramine, sold under the brand name Anafranil among others, is a tricyclic antidepressant (TCA). It is used in the treatment of various conditions, most-notably obsessive–compulsive disorder but also many other disorders, including hyperacusis, panic disorder, major depressive disorder, trichotillomania, body dysmorphic disorder and chronic pain. It has also been notably used to treat premature ejaculation and the cataplexy associated with narcolepsy.

<span class="mw-page-title-main">Nortriptyline</span> Antidepressant medication

Nortriptyline, sold under the brand name Aventyl, among others, is a tricyclic antidepressant. This medicine is also sometimes used for neuropathic pain, attention deficit hyperactivity disorder (ADHD), smoking cessation and anxiety. As with many antidepressants, its use for young people with depression and other psychiatric disorders may be limited due to increased suicidality in the 18–24 population initiating treatment. Nortriptyline is a less preferred treatment for ADHD and stopping smoking. It is taken by mouth.

<span class="mw-page-title-main">Doxepin</span> Medication to treat depressive disorder, anxiety disorders, chronic hives, and trouble sleeping

Doxepin is a medication belonging to the tricyclic antidepressant (TCA) class of drugs used to treat major depressive disorder, anxiety disorders, chronic hives, and insomnia. For hives it is a less preferred alternative to antihistamines. It has a mild to moderate benefit for sleeping problems. It is used as a cream for itchiness due to atopic dermatitis or lichen simplex chronicus.

<span class="mw-page-title-main">Trimipramine</span> Antidepressant

Trimipramine, sold under the brand name Surmontil among others, is a tricyclic antidepressant (TCA) which is used to treat depression. It has also been used for its sedative, anxiolytic, and weak antipsychotic effects in the treatment of insomnia, anxiety disorders, and psychosis, respectively. The drug is described as an atypical or "second-generation" TCA because, unlike other TCAs, it seems to be a fairly weak monoamine reuptake inhibitor. Similarly to other TCAs, however, trimipramine does have antihistamine, antiserotonergic, antiadrenergic, antidopaminergic, and anticholinergic activities.

<span class="mw-page-title-main">Dosulepin</span> Antidepressant

Dosulepin, also known as dothiepin and sold under the brand name Prothiaden among others, is a tricyclic antidepressant (TCA) which is used in the treatment of depression. Dosulepin was once the most frequently prescribed antidepressant in the United Kingdom, but it is no longer widely used due to its relatively high toxicity in overdose without therapeutic advantages over other TCAs. It acts as a serotonin–norepinephrine reuptake inhibitor (SNRI) and also has other activities including antihistamine, antiadrenergic, antiserotonergic, anticholinergic, and sodium channel-blocking effects.

<span class="mw-page-title-main">Lofepramine</span> Chemical compound

Lofepramine, sold under the brand names Gamanil, Lomont, and Tymelyt among others, is a tricyclic antidepressant (TCA) which is used to treat depression. 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. 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.

<span class="mw-page-title-main">Protriptyline</span> Chemical compound

Protriptyline, sold under the brand name Vivactil among others, is a tricyclic antidepressant (TCA), specifically a secondary amine, indicated for the treatment of depression and attention-deficit hyperactivity disorder (ADHD). Uniquely among most of the TCAs, protriptyline tends to be energizing instead of sedating, and is sometimes used for narcolepsy to achieve a wakefulness-promoting effect.

<span class="mw-page-title-main">Iprindole</span> Atypical tricyclic antidepressant

Iprindole, sold under the brand names Prondol, Galatur, and Tertran, is an atypical tricyclic antidepressant (TCA) that has been used in the United Kingdom and Ireland for the treatment of depression but appears to no longer be marketed. It was developed by Wyeth and was marketed in 1967. The drug has been described by some as the first "second-generation" antidepressant to be introduced. However, it was very little-used compared to other TCAs, with the number of prescriptions dispensed only in the thousands.

<span class="mw-page-title-main">Noxiptiline</span> Chemical compound

Noxiptiline, also known as noxiptyline and dibenzoxine, is a tricyclic antidepressant (TCA) that was introduced in Europe in the 1970s for the treatment of depression. It has imipramine-like effects, acting as a serotonin and norepinephrine reuptake inhibitor, among other properties. Of the TCAs, noxiptiline has been described as one of the most effective, rivaling amitriptyline in clinical efficacy.

<span class="mw-page-title-main">Amitriptylinoxide</span> Chemical compound

Amitriptylinoxide, or amitriptyline N-oxide, is a tricyclic antidepressant (TCA) which was introduced in Europe in the 1970s for the treatment of depression.

<span class="mw-page-title-main">Imipraminoxide</span> Chemical compound

Imipraminoxide, or imipramine N-oxide, is a tricyclic antidepressant (TCA) that was introduced in Europe in the 1960s for the treatment of depression.

<span class="mw-page-title-main">Nordoxepin</span> Active metabolite of antidepressant drug doxepin

Nordoxepin, also known as N-desmethyldoxepin, is an organic compound. A colorless solid, it attracted attention as the major active metabolite of the tricyclic antidepressant (TCA) doxepin (Sinequan). It has been found to play a significant role in the antidepressant effects of doxepin.

References

  1. 1 2 3 4 5 6 7 Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 201–. ISBN   978-1-4757-2085-3.
  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. 1 2 3 4 5 Dörwald FZ (4 February 2013). "Dibenzazepines and Related Tricyclic Compounds". Lead Optimization for Medicinal Chemists: Pharmacokinetic Properties of Functional Groups and Organic Compounds. John Wiley & Sons. pp. 313–. ISBN   978-3-527-64565-7.
  4. 1 2 3 4 5 6 7 Swiss Pharmaceutical Society (2000). Index Nominum 2000: International Drug Directory (Book with CD-ROM). Boca Raton: Medpharm Scientific Publishers. ISBN   3-88763-075-0. Archived from the original on 2023-01-12. Retrieved 2020-10-30.
  5. 1 2 3 4 William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia. Elsevier. pp. 777–. ISBN   978-0-8155-1856-3.
  6. 1 2 Holenz J, Diaz JL, Buschmann H (16 April 2007). "Tricyclic and tetracyclic antidepressants". In Buschmann H (ed.). Antidepressants, Antipsychotics, Anxiolytics: From Chemistry and Pharmacology to Clinical Application. Wiley. pp. 180–. ISBN   978-3-527-31058-6.[ permanent dead link ]
  7. 1 2 Paykel ES (1992). Handbook of Affective Disorders. Guilford Press. pp. 339–. ISBN   978-0-89862-674-2.
  8. Sharma SS, Chawala P (18 November 2009). "Drug Therapy of Affective Disorders". In Seth A (ed.). Textbook Of Pharmacology. Elsevier India. pp. 119–. ISBN   978-81-312-1158-8.
  9. Bhattacharya A (2003). "Central Nervous System". Pharmacology (2nd ed.). Elsevier India. pp. 292–. ISBN   978-81-8147-009-6.
  10. 1 2 3 Aronson JK (2009). Meyler's Side Effects of Psychiatric Drugs. Elsevier. pp. 7, 18, 31. ISBN   978-0-444-53266-4. Archived from the original on 2024-07-26. Retrieved 2017-08-13.
  11. 1 2 Morton IK, Hall JM (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 58–. ISBN   978-94-011-4439-1.
  12. Paykel ES (29 October 1982). "Treatment for Affective Disorders". In Wing JK, Wing L (eds.). Handbook of Psychiatry: Volume 3, Psychoses of Uncertain Aetiology. CUP Archive. pp. 167–. ISBN   978-0-521-28438-7.
  13. 1 2 Gillman PK (July 2007). "Tricyclic antidepressant pharmacology and therapeutic drug interactions updated". British Journal of Pharmacology. 151 (6): 737–748. doi:10.1038/sj.bjp.0707253. PMC   2014120 . PMID   17471183.
  14. 1 2 Mumenthaler M, van Zwieten PA, Farcot JM, eds. (1990). "Reactions to Antidepressant Drugs and Lithium Salts". Treatment of Chronic Pain: Possibilities, Limitations, and Long-term Follow-up. CRC Press. pp. 114–. ISBN   978-3-7186-5027-9. Archived from the original on 2024-07-26. Retrieved 2017-08-13.
  15. 1 2 3 4 5 6 7 8 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. PMID   6086881.
  16. 1 2 3 4 5 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.
  17. 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. Archived from the original on 2 December 2023. Retrieved 14 August 2017.
  18. 1 2 3 4 Richelson E, Pfenning M (September 1984). "Blockade by antidepressants and related compounds of biogenic amine uptake into rat brain synaptosomes: most antidepressants selectively block norepinephrine uptake". European Journal of Pharmacology. 104 (3–4): 277–286. doi:10.1016/0014-2999(84)90403-5. PMID   6499924.
  19. 1 2 3 4 5 Randrup A, Braestrup C (August 1977). "Uptake inhibition of biogenic amines by newer antidepressant drugs: relevance to the dopamine hypothesis of depression". Psychopharmacology. 53 (3): 309–314. doi:10.1007/BF00492370. PMID   408861. S2CID   8183053.
  20. 1 2 3 4 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.
  21. Jaramillo J, Greenberg R (February 1975). "Comparative pharmacological studies on butriptyline and some related standard tricyclic antidepressants". Canadian Journal of Physiology and Pharmacology. 53 (1): 104–112. doi:10.1139/y75-014. PMID   166748.
  22. Stuart S (22 October 2013). "Tricyclic Antidepressants". Drugs in Psychiatric Practice. Elsevier. pp. 194–. ISBN   978-1-4831-9193-5. Archived from the original on 26 July 2024. Retrieved 13 August 2017.
  23. Smith RN (6 December 2012). "Radioimmunoassay of Drugs in Body Fluids in a Forensic Context". In Maehly A, Williams RL (eds.). Forensic Science Progress. Springer Science & Business Media. pp. 24–. ISBN   978-3-642-73058-0.
  24. 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.
  25. Zavod RM, Knittel JJ (24 January 2012). "Drug Design and Relationship of Functional Groups to Pharmacological Activity". In Lemke TL, Williams DA (eds.). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 604–. ISBN   978-1-60913-345-0. Archived from the original on 12 January 2023. Retrieved 13 August 2017.
  26. Dawkins K, Manji HK, Potter WZ (20 September 1994). "Pharmacodynamics of Antidepressants". In Cutler NR, Sramek JJ, Narang PK (eds.). Pharmacodynamics and Drug Development: Perspectives in Clinical Pharmacology. John Wiley & Sons. pp. 160–. ISBN   978-0-471-95052-3.
  27. 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.
  28. Anthony PK (2002). "Drugs Used in the Therapy of Depression". Pharmacology Secrets. Elsevier Health Sciences. pp. 39–. ISBN   1-56053-470-2. Archived from the original on 2023-01-10. Retrieved 2017-08-16.
  29. Cowen P, Harrison P, Burns T (9 August 2012). "Drugs and Other Physical Treatments". Shorter Oxford Textbook of Psychiatry. OUP Oxford. pp. 532–. ISBN   978-0-19-162675-3. Archived from the original on 10 January 2023. Retrieved 16 August 2017.
  30. Ghose K (11 November 2013). "Side-effects of tricyclic and related antidepressants". In Ghose K (ed.). Antidepressants for Elderly People. Springer. pp. 182–. ISBN   978-1-4899-3436-9. Archived from the original on 14 January 2023. Retrieved 13 August 2017.
  31. Dawson AH (2004). "Cyclic Antidepressant Drugs". In Dart RC (ed.). Medical Toxicology. Lippincott Williams & Wilkins. pp. 836–. ISBN   978-0-7817-2845-4.