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Details

Stereochemistry ABSOLUTE
Molecular Formula C22H31NO.C4H6O6
Molecular Weight 475.5755
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TOLTERODINE TARTRATE

SMILES

CC(C)N(CC[C@]([H])(c1ccccc1)c2cc(C)ccc2O)C(C)C.[C@@]([H])([C@]([H])(C(=O)O)O)(C(=O)O)O

InChI

InChIKey=TWHNMSJGYKMTRB-KXYUELECSA-N
InChI=1S/C22H31NO.C4H6O6/c1-16(2)23(17(3)4)14-13-20(19-9-7-6-8-10-19)21-15-18(5)11-12-22(21)24;5-1(3(7)8)2(6)4(9)10/h6-12,15-17,20,24H,13-14H2,1-5H3;1-2,5-6H,(H,7,8)(H,9,10)/t20-;1-,2-/m11/s1

HIDE SMILES / InChI

Molecular Formula C4H6O6
Molecular Weight 150.087
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula C22H31NO
Molecular Weight 325.4885
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Tolterodine is competitive muscarinic receptors M3 and M2 antagonist. It was sold under trade names detrol for the treatment of overactive bladder with symptoms of urge urinary incontinence. Both urinary bladder contraction and salivation are mediated via cholinergic muscarinic receptors. After oral administration, tolterodine is metabolized in the liver, resulting in the formation of the 5-hydroxymethyl derivative, a major pharmacologically active metabolite. The 5-hydroxymethyl metabolite, which exhibits an antimuscarinic activity similar to that of tolterodine, contributes significantly to the therapeutic effect. Both tolterodine and the 5-hydroxymethyl metabolite exhibit a high specificity for muscarinic receptors, since both show negligible activity and affinity for other neurotransmitter receptors and other potential cellular targets, such as calcium channels. Tolterodine has a pronounced effect on bladder function. The main effects of tolterodine at 1 and 5 hours were an increase in residual urine, reflecting an incomplete emptying of the bladder, and a decrease in detrusor pressure. These findings are consistent with an antimuscarinic action on the lower urinary tract.

CNS Activity

Curator's Comment:: Both oxybutynin and tolterodine are tertiary amines that cross the blood-brain barrier. However, tolterodine is 30 times less lipophilic than oxybutynin.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
DETROL

Approved Use

Tolterodine tartrate extended-release capsules are indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency [see CLINICAL STUDIES (14)

Launch Date

8.9078399E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.8 μg/L
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TOLTERODINE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: HIGH-FAT
2.3 μg/L
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TOLTERODINE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: FASTED
1.6 μg/L
4 mg single, oral
dose: 4 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TOLTERODINE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
10 μg/L
4 mg single, oral
dose: 4 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TOLTERODINE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
19 μg/L
4 mg 2 times / day multiple, oral
dose: 4 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TOLTERODINE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
2.6 μg/L
4 mg 2 times / day multiple, oral
dose: 4 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TOLTERODINE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
23 μg × h/L
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TOLTERODINE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: HIGH-FAT
27 μg × h/L
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TOLTERODINE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
8.1 h
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TOLTERODINE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: HIGH-FAT
7.9 h
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TOLTERODINE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: FASTED
2 h
4 mg single, oral
dose: 4 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TOLTERODINE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
6.5 h
4 mg single, oral
dose: 4 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TOLTERODINE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
9.6 h
4 mg 2 times / day multiple, oral
dose: 4 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TOLTERODINE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
2.2 h
4 mg 2 times / day multiple, oral
dose: 4 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TOLTERODINE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
2 mg 2 times / day multiple, oral
Recommended
Dose: 2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 2 mg, 2 times / day
Sources: Page: p.804
unhealthy, 20-93
n = 507
Health Status: unhealthy
Condition: Overactive bladder
Age Group: 20-93
Sex: M+F
Population Size: 507
Sources: Page: p.804
Disc. AE: Dry mouth...
AEs leading to
discontinuation/dose reduction:
Dry mouth (2.4%)
Sources: Page: p.804
4 mg 2 times / day multiple, oral
Highest studied dose
Dose: 4 mg, 2 times / day
Route: oral
Route: multiple
Dose: 4 mg, 2 times / day
Sources: Page: p.997
unhealthy, 52
n = 58
Health Status: unhealthy
Condition: Overactive bladder
Age Group: 52
Sex: M+F
Population Size: 58
Sources: Page: p.997
Disc. AE: Urinary retention...
AEs leading to
discontinuation/dose reduction:
Urinary retention (6.9%)
Sources: Page: p.997
2 mg 2 times / day multiple, oral
Recommended
Dose: 2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 2 mg, 2 times / day
Sources: Page: p.11
unhealthy
n = 986
Health Status: unhealthy
Condition: Overactive bladder
Sex: M+F
Population Size: 986
Sources: Page: p.11
Disc. AE: Dry mouth, Dizziness...
AEs leading to
discontinuation/dose reduction:
Dry mouth (1%)
Dizziness (common)
Headache (common)
Sources: Page: p.11
AEs

AEs

AESignificanceDosePopulation
Dry mouth 2.4%
Disc. AE
2 mg 2 times / day multiple, oral
Recommended
Dose: 2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 2 mg, 2 times / day
Sources: Page: p.804
unhealthy, 20-93
n = 507
Health Status: unhealthy
Condition: Overactive bladder
Age Group: 20-93
Sex: M+F
Population Size: 507
Sources: Page: p.804
Urinary retention 6.9%
Disc. AE
4 mg 2 times / day multiple, oral
Highest studied dose
Dose: 4 mg, 2 times / day
Route: oral
Route: multiple
Dose: 4 mg, 2 times / day
Sources: Page: p.997
unhealthy, 52
n = 58
Health Status: unhealthy
Condition: Overactive bladder
Age Group: 52
Sex: M+F
Population Size: 58
Sources: Page: p.997
Dry mouth 1%
Disc. AE
2 mg 2 times / day multiple, oral
Recommended
Dose: 2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 2 mg, 2 times / day
Sources: Page: p.11
unhealthy
n = 986
Health Status: unhealthy
Condition: Overactive bladder
Sex: M+F
Population Size: 986
Sources: Page: p.11
Dizziness common
Disc. AE
2 mg 2 times / day multiple, oral
Recommended
Dose: 2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 2 mg, 2 times / day
Sources: Page: p.11
unhealthy
n = 986
Health Status: unhealthy
Condition: Overactive bladder
Sex: M+F
Population Size: 986
Sources: Page: p.11
Headache common
Disc. AE
2 mg 2 times / day multiple, oral
Recommended
Dose: 2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 2 mg, 2 times / day
Sources: Page: p.11
unhealthy
n = 986
Health Status: unhealthy
Condition: Overactive bladder
Sex: M+F
Population Size: 986
Sources: Page: p.11
PubMed

PubMed

TitleDatePubMed
Fluoxetine inhibits the metabolism of tolterodine-pharmacokinetic implications and proposed clinical relevance.
1999 Oct
The overactive bladder in children: a potential future indication for tolterodine.
2001 Apr
Functional characterization of rat submaxillary gland muscarinic receptors using microphysiometry.
2001 Apr
Cost-Effectiveness of tolterodine for patients with urge incontinence who discontinue initial therapy with oxybutynin: a Canadian perspective.
2001 Dec
Pharmacokinetics of tolterodine, a muscarinic receptor antagonist, in mouse, rat and dog. Interspecies relationship comparing with human pharmacokinetics.
2001 Feb
Pharmacological characterization of muscarinic receptors in dog isolated ciliary and urinary bladder smooth muscle.
2001 Feb
Failure of tolterodine to treat clozapine-induced nocturnal enuresis.
2001 Jul-Aug
Overactive bladder: optimizing quality of care.
2001 Mar
Use of tolterodine in children with dysfunctional voiding: an initial report.
2001 Mar
The minor population of M3-receptors mediate contraction of human detrusor muscle in vitro.
2001 Oct-Dec
[Continence problems after radical prostatectomy: medical treatment].
2001 Sep
Gateways to Clinical Trials.
2002 Apr
Methodologic shortcomings inherent in a post-hoc analysis.
2002 Dec
Once-daily, extended-release formulations of antimuscarinic agents in the treatment of overactive bladder: a review.
2002 Jan
Risk of delirium with concomitant use of tolterodine and acetylcholinesterase inhibitors.
2002 Jun
Long-term safety, tolerability and efficacy of extended-release tolterodine in the treatment of overactive bladder.
2002 Jun
Muscarinic receptor antagonist-induced lenticular opacity in rats.
2002 Mar
Tolterodine: as effective but better tolerated than oxybutynin in Asian patients with symptoms of overactive bladder.
2002 May
Tolterodine-associated acute mixed liver injury.
2002 May
Assessment and conservative management of the neuropathic bladder.
2002 May
Gateways to Clinical Trials.
2002 Sep
Does gender or age affect the efficacy and safety of tolterodine?
2002 Sep
New treatment options for overactive bladder and incontinence.
2002 Summer
A new once-daily formulation of tolterodine provides superior efficacy and is well tolerated in women with overactive bladder.
2003 Feb
In vivo evaluation of the potency and bladder-vascular selectivity of the ATP-sensitive potassium channel openers (-)-cromakalim, ZD6169 and WAY-133537 in rats.
2003 Feb
Patents

Sample Use Guides

The initial recommended dose of DETROL (tolterodine tartrate tablets) is 2 mg twice daily. The dose may be lowered to 1 mg twice daily based on individual response and tolerability. For patients with significantly reduced hepatic or renal function or who are currently taking drugs that are potent inhibitors of CYP3A4, the recommended dose of DETROL is 1 mg twice daily
Route of Administration: Oral
In Vitro Use Guide
It was compared the antimuscarinic properties of tolterodine with those of oxybutynin, in vitro and in vivo. Tolterodine effectively inhibited carbachol-induced contractions of isolated strips of urinary bladder from guinea pigs (K(B) 3.0 nM; pA2 8.6; Schild slope 0.97) and humans (K(B) 4.0 nM; pA2 8.4; Schild slope 1.04) in a concentration-dependent, competitive manner. The affinity of tolterodine was similar to that derived for oxybutynin (K(B) 4.4 nM; pA2 8.5; Schild slope 0.89) in the guinea-pig bladder. Radioligand binding data showed that tolterodine bound with high affinity to muscarinic receptors in urinary bladder (K(i) 2.7 nM), heart (K(i) 1.6 nM), cerebral cortex (K(i) 0.75 nM) and parotid gland (K(i) 4.8 nM) from guinea pigs and in urinary bladder from humans (K(i) 3.3 nM). The combined in vitro and in vivo data on tolterodine and oxybutynin may indicate either that muscarinic M3/m3 receptors in glands are more sensitive to blockade than those in bladder smooth muscle, or that muscarinic M2/m2 receptors contribute to bladder contraction.
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:07:01 UTC 2021
Edited
by admin
on Fri Jun 25 21:07:01 UTC 2021
Record UNII
5T619TQR3R
Record Status Validated (UNII)
Record Version
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Name Type Language
TOLTERODINE TARTRATE
JAN   MART.   MI   ORANGE BOOK   USAN   USP-RS   VANDF  
USAN  
Official Name English
TOLTERODINE TARTRATE [MART.]
Common Name English
(R)-2-(3-(BIS(1-METHYLETHYL)AMINO)-1-PHENYLPROPYL)-4-METHYLPHENOL (R-(R*,R*))-2,3-DIHYDROXYBUTANEDIOATE (1:1) (SALT)
Common Name English
TOLTERODINE TARTRATE [VANDF]
Common Name English
PNU-200583E
Code English
DETROL
Brand Name English
TOLTERODINE TARTRATE [USP-RS]
Common Name English
TOLTERODINE L-TARTRATE
WHO-DD  
Common Name English
TOLTERODINE TARTRATE [ORANGE BOOK]
Common Name English
TOLTERODINE TARTRATE [USAN]
Common Name English
TOLTERODINE TARTRATE [JAN]
Common Name English
(+)-(R)-2-(I-(2-(DIISOPROPYLAMINO)ETHYL)BENZYL)-P-CRESOL L-TARTRATE (1:1) (SALT)
Common Name English
TOLTERODINE TARTRATE [MI]
Common Name English
TOLTERODINE TARTRATE [USP MONOGRAPH]
Common Name English
DETRUSITOL
Brand Name English
TOLTERODINE L-TARTRATE [WHO-DD]
Common Name English
TOLTERODINE TARTRATE [EP MONOGRAPH]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C29704
Created by admin on Fri Jun 25 21:07:01 UTC 2021 , Edited by admin on Fri Jun 25 21:07:01 UTC 2021
Code System Code Type Description
DRUG BANK
DBSALT000467
Created by admin on Fri Jun 25 21:07:01 UTC 2021 , Edited by admin on Fri Jun 25 21:07:01 UTC 2021
PRIMARY
PUBCHEM
443878
Created by admin on Fri Jun 25 21:07:01 UTC 2021 , Edited by admin on Fri Jun 25 21:07:01 UTC 2021
PRIMARY
MERCK INDEX
M10954
Created by admin on Fri Jun 25 21:07:01 UTC 2021 , Edited by admin on Fri Jun 25 21:07:01 UTC 2021
PRIMARY Merck Index
EVMPD
SUB15587MIG
Created by admin on Fri Jun 25 21:07:01 UTC 2021 , Edited by admin on Fri Jun 25 21:07:01 UTC 2021
PRIMARY
FDA UNII
5T619TQR3R
Created by admin on Fri Jun 25 21:07:01 UTC 2021 , Edited by admin on Fri Jun 25 21:07:01 UTC 2021
PRIMARY
NCI_THESAURUS
C29504
Created by admin on Fri Jun 25 21:07:01 UTC 2021 , Edited by admin on Fri Jun 25 21:07:01 UTC 2021
PRIMARY
EVMPD
SUB61874
Created by admin on Fri Jun 25 21:07:01 UTC 2021 , Edited by admin on Fri Jun 25 21:07:01 UTC 2021
PRIMARY
ChEMBL
CHEMBL1382
Created by admin on Fri Jun 25 21:07:01 UTC 2021 , Edited by admin on Fri Jun 25 21:07:01 UTC 2021
PRIMARY
CAS
124937-52-6
Created by admin on Fri Jun 25 21:07:01 UTC 2021 , Edited by admin on Fri Jun 25 21:07:01 UTC 2021
PRIMARY
RXCUI
221174
Created by admin on Fri Jun 25 21:07:01 UTC 2021 , Edited by admin on Fri Jun 25 21:07:01 UTC 2021
PRIMARY RxNorm
USP_CATALOG
1671480
Created by admin on Fri Jun 25 21:07:01 UTC 2021 , Edited by admin on Fri Jun 25 21:07:01 UTC 2021
PRIMARY USP-RS
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ACTIVE MOIETY