U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C22H31NO
Molecular Weight 325.4885
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TOLTERODINE

SMILES

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

InChI

InChIKey=OOGJQPCLVADCPB-HXUWFJFHSA-N
InChI=1S/C22H31NO/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/h6-12,15-17,20,24H,13-14H2,1-5H3/t20-/m1/s1

HIDE SMILES / InChI
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
Safety profile of tolterodine as used in general practice in England: results of prescription-event monitoring.
2001
Treatment of overactive bladder: long-term tolerability and efficacy of tolterodine.
2001 Apr
Costs and resources associated with the treatment of overactive bladder using retrospective medical care claims data.
2001 Aug
Practice patterns in the treatment of female urinary incontinence: a postal and internet survey.
2001 Jan
Tolterodine: a safe and effective treatment for older patients with overactive bladder.
2001 Jun
Effects of tolterodine, trospium chloride, and oxybutynin on the central nervous system.
2001 Jun
Clarification--Drug risk in patients with glaucoma.
2001 Jun 11
Tolterodine once-daily: superior efficacy and tolerability in the treatment of the overactive bladder.
2001 Mar
Tolterodine: superior tolerability than and comparable efficacy to oxybutynin in individuals 50 years old or older with overactive bladder: a randomized controlled trial.
2001 May
[An example of interactions between SSRI preparations and tolterodine?].
2001 May 2
The effect of tolterodine on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive containing ethinyl estradiol and levonorgestrel.
2001 Nov
POEMS (patient-oriented evidence that matters) spark discussion.
2001 Oct
Effect of tolterodine on the anticoagulant actions and pharmacokinetics of single-dose warfarin in healthy volunteers.
2002
Treatment of overactive bladder with once-daily extended-release tolterodine or oxybutynin: the antimuscarinic clinical effectiveness trial (ACET).
2002
Tolterodine: selectivity for the urinary bladder over the eye (as measured by visual accommodation) in healthy volunteers.
2002
Gateways to Clinical Trials.
2002 Apr
Tolterodine: a safe and effective treatment for older patients with overactive bladder.
2002 Apr
Health-related quality of life of patients receiving extended-release tolterodine for overactive bladder.
2002 Dec
Gateways to clinical trials.
2002 Jan-Feb
Gateways to clinical trials.
2002 Jul-Aug
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
Efficacy of botulinum-a toxin in children with detrusor hyperreflexia due to myelomeningocele: preliminary results.
2002 Mar
Pharmacotherapy of the overactive bladder and advances in drug delivery.
2002 Mar
Muscarinic receptor antagonist-induced lenticular opacity in rats.
2002 Mar
Achieving bladder control. Treatment in the primary care setting.
2002 May
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
Muscarinic receptor subtypes and management of the overactive bladder.
2002 Nov
Conservative management in neurogenic bladder dysfunction.
2002 Nov
Different responses to drugs against overactive bladder in detrusor muscle of pig, guinea pig and mouse.
2002 Nov 1
The newer antimuscarinic drugs: bladder control with less dry mouth.
2002 Oct
Gateways to Clinical Trials.
2002 Sep
25-Hydroxylation of vitamin D3 in primary cultures of pig hepatocytes: evidence for a role of both CYP2D25 and CYP27A1.
2003 Apr 11
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.
Name Type Language
TOLTERODINE
INN   MI   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
TOLTERODINE [USAN]
Common Name English
TOLTERODINE [VANDF]
Common Name English
TOLTERODINE [WHO-DD]
Common Name English
KABI-2234
Code English
TOLTERODINE [MI]
Common Name English
TOLTERODINE [INN]
Common Name English
KABI 2234
Code English
Classification Tree Code System Code
NDF-RT N0000000125
Created by admin on Sat Jun 26 06:30:22 UTC 2021 , Edited by admin on Sat Jun 26 06:30:22 UTC 2021
LIVERTOX 979
Created by admin on Sat Jun 26 06:30:22 UTC 2021 , Edited by admin on Sat Jun 26 06:30:22 UTC 2021
NDF-RT N0000175700
Created by admin on Sat Jun 26 06:30:22 UTC 2021 , Edited by admin on Sat Jun 26 06:30:22 UTC 2021
WHO-VATC QG04BD07
Created by admin on Sat Jun 26 06:30:22 UTC 2021 , Edited by admin on Sat Jun 26 06:30:22 UTC 2021
NDF-RT N0000000125
Created by admin on Sat Jun 26 06:30:22 UTC 2021 , Edited by admin on Sat Jun 26 06:30:22 UTC 2021
WHO-ATC G04BD07
Created by admin on Sat Jun 26 06:30:22 UTC 2021 , Edited by admin on Sat Jun 26 06:30:22 UTC 2021
NCI_THESAURUS C29704
Created by admin on Sat Jun 26 06:30:22 UTC 2021 , Edited by admin on Sat Jun 26 06:30:22 UTC 2021
NDF-RT N0000000125
Created by admin on Sat Jun 26 06:30:22 UTC 2021 , Edited by admin on Sat Jun 26 06:30:22 UTC 2021
Code System Code Type Description
LACTMED
Tolterodine
Created by admin on Sat Jun 26 06:30:22 UTC 2021 , Edited by admin on Sat Jun 26 06:30:22 UTC 2021
PRIMARY
EVMPD
SUB11180MIG
Created by admin on Sat Jun 26 06:30:22 UTC 2021 , Edited by admin on Sat Jun 26 06:30:22 UTC 2021
PRIMARY
EPA CompTox
124937-51-5
Created by admin on Sat Jun 26 06:30:22 UTC 2021 , Edited by admin on Sat Jun 26 06:30:22 UTC 2021
PRIMARY
DRUG BANK
DB01036
Created by admin on Sat Jun 26 06:30:22 UTC 2021 , Edited by admin on Sat Jun 26 06:30:22 UTC 2021
PRIMARY
MERCK INDEX
M10954
Created by admin on Sat Jun 26 06:30:22 UTC 2021 , Edited by admin on Sat Jun 26 06:30:22 UTC 2021
PRIMARY Merck Index
ChEMBL
CHEMBL1382
Created by admin on Sat Jun 26 06:30:22 UTC 2021 , Edited by admin on Sat Jun 26 06:30:22 UTC 2021
PRIMARY
MESH
C099041
Created by admin on Sat Jun 26 06:30:22 UTC 2021 , Edited by admin on Sat Jun 26 06:30:22 UTC 2021
PRIMARY
DRUG CENTRAL
2705
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PRIMARY
INN
6768
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PRIMARY
CAS
124937-51-5
Created by admin on Sat Jun 26 06:30:22 UTC 2021 , Edited by admin on Sat Jun 26 06:30:22 UTC 2021
PRIMARY
WIKIPEDIA
TOLTERODINE
Created by admin on Sat Jun 26 06:30:22 UTC 2021 , Edited by admin on Sat Jun 26 06:30:22 UTC 2021
PRIMARY
PUBCHEM
443879
Created by admin on Sat Jun 26 06:30:22 UTC 2021 , Edited by admin on Sat Jun 26 06:30:22 UTC 2021
PRIMARY
IUPHAR
360
Created by admin on Sat Jun 26 06:30:22 UTC 2021 , Edited by admin on Sat Jun 26 06:30:22 UTC 2021
PRIMARY
FDA UNII
WHE7A56U7K
Created by admin on Sat Jun 26 06:30:22 UTC 2021 , Edited by admin on Sat Jun 26 06:30:22 UTC 2021
PRIMARY
NCI_THESAURUS
C62083
Created by admin on Sat Jun 26 06:30:22 UTC 2021 , Edited by admin on Sat Jun 26 06:30:22 UTC 2021
PRIMARY
RXCUI
119565
Created by admin on Sat Jun 26 06:30:22 UTC 2021 , Edited by admin on Sat Jun 26 06:30:22 UTC 2021
PRIMARY RxNorm