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Details

Stereochemistry ABSOLUTE
Molecular Formula C22H31NO.ClH
Molecular Weight 361.9493
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TOLTERODINE HYDROCHLORIDE

SMILES

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

InChI

InChIKey=FSUOGWPKKKHHHM-VEIFNGETSA-N
InChI=1S/C22H31NO.ClH/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;1H/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

Molecular Formula ClH
Molecular Weight 36.4609
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
Twelve-month treatment of overactive bladder: efficacy and tolerability of tolterodine.
2001
Prospective randomized controlled trial of extended-release oxybutynin chloride and tolterodine tartrate in the treatment of overactive bladder: results of the OBJECT Study.
2001 Apr
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
Detrol LA and Diropan XL for overactive bladder.
2001 Apr 2
Clinical experiences with tolterodine.
2001 Apr 27
Pharmacological characterization of muscarinic receptors in mouse isolated urinary bladder smooth muscle.
2001 Aug
Is tolterodine (Detrol) or oxybutynin (Ditropan) the best for treatment of urge urinary incontinence?
2001 Dec
Tolterodine versus oxybutynin in the treatment of urge urinary incontinence: a meta-analysis.
2001 Jul
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
Food increases the bioavailability of tolterodine but not effective exposure.
2001 Mar
Overactive bladder: optimizing quality of care.
2001 Mar
A comparison of the effects on saliva output of oxybutynin chloride and tolterodine tartrate.
2001 May
[An example of interactions between SSRI preparations and tolterodine?].
2001 May 2
Tolterodine once-daily in treatment of the overactive bladder.
2001 Nov
Tolterodine: a clinical review.
2001 Oct
POEMS (patient-oriented evidence that matters) spark discussion.
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
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
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
Advances in drug delivery: improved bioavailability and drug effect.
2002 Dec
Methodologic shortcomings inherent in a post-hoc analysis.
2002 Dec
Medication update.
2002 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
Pharmacotherapy of the overactive bladder and advances in drug delivery.
2002 Mar
Achieving bladder control. Treatment in the primary care setting.
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
Pharmacologic treatment for detrusor overactivity.
2002 Oct
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 13:14:14 UTC 2021
Edited
by admin
on Sat Jun 26 13:14:14 UTC 2021
Record UNII
75I47Y48S7
Record Status Validated (UNII)
Record Version
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Name Type Language
TOLTERODINE HYDROCHLORIDE
Common Name English
2-((1R)-3-(DIISOPROPYLAMINO)-1-PHENYLPROPYL)-4-METHYLPHENOL HYDROCHLORIDE (1:1)
Systematic Name English
Code System Code Type Description
CAS
124936-75-0
Created by admin on Sat Jun 26 13:14:15 UTC 2021 , Edited by admin on Sat Jun 26 13:14:15 UTC 2021
PRIMARY
FDA UNII
75I47Y48S7
Created by admin on Sat Jun 26 13:14:15 UTC 2021 , Edited by admin on Sat Jun 26 13:14:15 UTC 2021
PRIMARY
PUBCHEM
46911937
Created by admin on Sat Jun 26 13:14:15 UTC 2021 , Edited by admin on Sat Jun 26 13:14:15 UTC 2021
PRIMARY
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PARENT -> SALT/SOLVATE
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ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC