Butriptyline

Butriptyline

Clinical data
Trade names	Evadyne, others
Other names	AY-62014 [1]
Routes of administration	Oral
ATC code	N06AA15 ( WHO )
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
IUPAC name (±)-3-(10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-yl)-N,N,2-trimethylpropan-1-amine
CAS Number	35941-65-2  Y HCl:  5585-73-9  Y
PubChem CID	21772
DrugBank	DB09016  N
ChemSpider	20462  Y
UNII	Z22441975X HCl:  LIJ2H8658W  Y
KEGG	D07601  Y
ChEBI	CHEBI:135227  Y
ChEMBL	ChEMBL2110816  N
CompTox Dashboard (EPA)	DTXSID6022715
Chemical and physical data
Formula	C21H27N
Molar mass	293.454 g·mol−1
3D model (JSmol)	Interactive image
Chirality	Racemic 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 Y Key:ALELTFCQZDXAMQ-UHFFFAOYSA-N Y
NY  (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

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

Main article: Tricyclic antidepressant overdose

Pharmacology

Pharmacodynamics

See also: Pharmacology of antidepressants and Tricyclic antidepressant § Binding profiles

Butriptyline ^[17]

Site	Ki (nM)	Species	Ref
SERT Tooltip Serotonin transporter	1,360 4,300 10,000 (IC50 Tooltip Half-maximal inhibitory concentration)	Human Rat Rat	[16] [18] [19]
NET Tooltip Norepinephrine transporter	5,100 990 1,700 (IC50)	Human Rat Rat	[16] [18] [19]
DAT Tooltip 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]
mACh Tooltip 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

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]}

References

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