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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

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
Cost-Effectiveness of tolterodine for patients with urge incontinence who discontinue initial therapy with oxybutynin: a Canadian perspective.
2001 Dec
The effect of tolterodine on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive containing ethinyl estradiol and levonorgestrel.
2001 Nov
Evidence for the efficacy and safety of tolterodine in the treatment of overactive bladder.
2001 Oct
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
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
Anticholinergic drugs versus placebo for overactive bladder syndrome in adults.
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
A multicenter, prospective, open-label study of tolterodine extended-release 4 mg for overactive bladder: the speed of onset of therapeutic assessment trial (STAT).
2002 Apr
Tolterodine: a safe and effective treatment for older patients with overactive bladder.
2002 Apr
Long-term health-related quality of life of patients receiving extended-release tolterodine for overactive bladder.
2002 Dec
Health-related quality of life of patients receiving extended-release tolterodine for overactive bladder.
2002 Dec
Medication update.
2002 Feb
Once-daily, extended-release formulations of antimuscarinic agents in the treatment of overactive bladder: a review.
2002 Jan
Gateways to clinical trials.
2002 Jan-Feb
Comparison of laparoscopic Burch and tension-free vaginal tape in treating stress urinary incontinence in obese patients.
2002 Jan-Mar
Gateways to clinical trials.
2002 Jul-Aug
Risk of delirium with concomitant use of tolterodine and acetylcholinesterase inhibitors.
2002 Jun
Effect of muscarinic antagonists on micturition pressure measured by cystometry in normal, conscious rats.
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
Tolterodine and its active 5-hydroxymethyl metabolite: pure muscarinic receptor antagonists.
2002 May
Tolterodine: as effective but better tolerated than oxybutynin in Asian patients with symptoms of overactive bladder.
2002 May
Efficacy, safety, and tolerability of extended-release once-daily tolterodine treatment for overactive bladder in older versus younger patients.
2002 May
Tolterodine-associated acute mixed liver injury.
2002 May
Assessment and conservative management of the neuropathic bladder.
2002 May
Overactive bladder patients and role of the pharmacist.
2002 May-Jun
Muscarinic receptor subtypes and management of the overactive bladder.
2002 Nov
Human variability in polymorphic CYP2D6 metabolism: is the kinetic default uncertainty factor adequate?
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
Pharmacologic treatment for detrusor overactivity.
2002 Oct
Treatment of overactive bladder: the Antimuscarinic Clinical Effectiveness Trial.
2002 Oct
The subtypes of muscarinic receptors for neurogenic bladder contraction in rats.
2002 Oct 4
Gateways to Clinical Trials.
2002 Sep
Does gender or age affect the efficacy and safety of tolterodine?
2002 Sep
A randomized controlled trial of tolterodine and oxybutynin on tolerability and clinical efficacy for treating Chinese women with an overactive bladder.
2002 Sep
Characterization of a new muscarinic receptor antagonist PNU-171990 in guinea pig, cat and human smooth muscle.
2002 Sep 13
Treatment can lead to a long dry spell.
2002 Spring
New treatment options for overactive bladder and incontinence.
2002 Summer
Effects of ATP-sensitive K+ channel openers and tolterodine on involuntary bladder contractions in a pig model of partial bladder outlet obstruction.
2003
25-Hydroxylation of vitamin D3 in primary cultures of pig hepatocytes: evidence for a role of both CYP2D25 and CYP27A1.
2003 Apr 11
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
Simplified bladder training augments the effectiveness of tolterodine in patients with an overactive bladder.
2003 Jan
Therapeutic efficacy of extended release oxybutynin chloride, and immediate release and long acting tolterodine tartrate in children with diurnal urinary incontinence.
2003 Jan
The use of tolterodine in children after oxybutynin failure.
2003 Mar
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 Sat Jun 26 06:30:21 UTC 2021
Edited
by admin
on Sat Jun 26 06:30:21 UTC 2021
Record UNII
WHE7A56U7K
Record Status Validated (UNII)
Record Version
  • Download
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
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
INN
6768
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
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
Related Record Type Details
TARGET -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
MAJOR
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
TARGET -> INHIBITOR
TARGET -> INHIBITOR
BINDER->LIGAND
TARGET -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
MAJOR
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
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METABOLITE -> PARENT
IN-VITRO
METABOLITE -> PARENT
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METABOLITE -> PARENT
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METABOLITE ACTIVE -> PARENT
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ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC