Butriptyline

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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

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<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, 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">Serotonin–norepinephrine reuptake inhibitor</span> Class of antidepressant medication

Serotonin–norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressant medications used to treat major depressive disorder (MDD), anxiety disorders, obsessive–compulsive disorder (OCD), social phobia, attention-deficit hyperactivity disorder (ADHD), chronic neuropathic pain, fibromyalgia syndrome (FMS), and menopausal symptoms. SNRIs are monoamine reuptake inhibitors; specifically, they inhibit the reuptake of serotonin and norepinephrine. These neurotransmitters are thought to play an important role in mood regulation. SNRIs can be contrasted with the selective serotonin reuptake inhibitors (SSRIs) and norepinephrine reuptake inhibitors (NRIs), which act upon single neurotransmitters.

<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, especially obsessive–compulsive disorder but also many other disorders, including panic disorder, major depressive disorder, trichotilomania, 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 Pamelor, among others, is a medication used to treat depression. 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

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<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

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

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

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

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<span class="mw-page-title-main">Serotonin reuptake inhibitor</span> Class of drug

A serotonin reuptake inhibitor (SRI) is a type of drug which acts as a reuptake inhibitor of the neurotransmitter serotonin by blocking the action of the serotonin transporter (SERT). This in turn leads to increased extracellular concentrations of serotonin and, therefore, an increase in serotonergic neurotransmission. It is a type of monoamine reuptake inhibitor (MRI); other types of MRIs include dopamine reuptake inhibitors and norepinephrine reuptake inhibitors.

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

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<span class="mw-page-title-main">Serotonin–dopamine reuptake inhibitor</span> Class of drug

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