Table of Contents
Categories
  • Dibenzocycloheptenes
  • H1 receptor antagonists
  • Muscarinic antagonists
  • Serotonin receptor antagonists
  • Tricyclic antidepressants
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    Butriptyline

    From Wikipedia - Reading time: 21 min
    Butriptyline
    Clinical data
    Trade namesEvadyne, 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]
    MetabolismHepatic (N-demethylation)
    MetabolitesNorbutriptyline[3]
    Elimination half-life20 hours[3]
    Identifiers
    IUPAC name
    • (±)-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
    FormulaC21H27N
    Molar mass293.454 g·mol−1
    3D model (JSmol)
    ChiralityRacemic mixture
    SMILES
    • c1cc3c(cc1)CCc2c(cccc2)C3CC(C)CN(C)C
    InChI
    • 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 checkY
    • Key:ALELTFCQZDXAMQ-UHFFFAOYSA-N checkY
     ☒NcheckY (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]

    Medical uses[edit]

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

    Side effects[edit]

    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[edit]

    Main article: Tricyclic antidepressant overdose

    Pharmacology[edit]

    Pharmacodynamics[edit]

    See also: Pharmacology of antidepressants and Tricyclic antidepressant § Binding profiles
    Butriptyline[17]
    Site Ki (nM) Species Ref
    SERTTooltip Serotonin transporter 1,360
    4,300
    10,000 (IC50Tooltip Half-maximal inhibitory concentration)    		 Human
    Rat
    Rat    		 [16]
    [18]
    [19]
    NETTooltip Norepinephrine transporter 5,100
    990
    1,700 (IC50)    		 Human
    Rat
    Rat    		 [16]
    [18]
    [19]
    DATTooltip Dopamine transporter 3,940
    2,800
    5,200 (IC50)    		 Human
    Rat
    Rat    		 [16]
    [18]
    [19]
    5-HT1A 7,000 Human [20]
    5-HT2A 380 Human [20]
    5-HT2C ND ND ND
    α1 570 Human [15]
    α2 4,800 Human [15]
    D2 ND ND ND
    H1 1.1 Human [15]
    mAChTooltip Muscarinic acetylcholine receptor 35 Human [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[edit]

    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[edit]

    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[edit]

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

    Society and culture[edit]

    Generic names[edit]

    Butriptyline is the English and French generic name of the drug and its INNTooltip International Nonproprietary Name, BANTooltip British Approved Name, and DCFTooltip Dénomination Commune Française, while butriptyline hydrochloride is its BANMTooltip British Approved Name and USANTooltip 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[edit]

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

    Availability[edit]

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

    References[edit]

    1. ^ a b c d e f g J. Elks (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. ^ a b c d e Florencio Zaragoza Dörwald (4 February 2013). Lead Optimization for Medicinal Chemists: Pharmacokinetic Properties of Functional Groups and Organic Compounds. John Wiley & Sons. pp. 313–. ISBN 978-3-527-64565-7.
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    14. ^ a b Marco Mumenthaler; P. A. van Zwieten; Jean Marie Farcot (1990). Treatment of Chronic Pain: Possibilities, Limitations, and Long-term Follow-up. CRC Press. pp. 114–. ISBN 978-3-7186-5027-9.
    15. ^ a b c d e f g h Richelson E, Nelson A (1984). "Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro". J. Pharmacol. Exp. Ther. 230 (1): 94–102. PMID 6086881.
    16. ^ a b c d e Tatsumi M, Groshan K, Blakely RD, Richelson E (1997). "Pharmacological profile of antidepressants and related compounds at human monoamine transporters". Eur. J. Pharmacol. 340 (2–3): 249–58. 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. Retrieved 14 August 2017.
    18. ^ a b c d 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): 277–86. doi:10.1016/0014-2999(84)90403-5. PMID 6499924.
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