TOLTERODINE HYDROCHLORIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H31NO.ClH
Molecular Weight	361.949
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CC(C)N(CC[C@H](C1=CC=CC=C1)C2=C(O)C=CC(C)=C2)C(C)C

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	325.4876
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020771s022lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/16465186

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

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Muscarinic acetylcholine receptor M3 159 Target ID: CHEMBL245 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16465186	Antagonist 2778
Muscarinic acetylcholine receptor M2 121 Target ID: CHEMBL211 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16465186	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Overactive bladder 38 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020771s022lbl.pdf	Primary		Approved 8429	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 1998

C_max

Value	Dose	Analyte	Population
1.8 μg/L OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21-228_Detrol%20LA_BioPharmr.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21-228_Detrol%20LA_BioPharmr.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21-228_Detrol%20LA_BioPharmr.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21-228_Detrol%20LA_BioPharmr.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21-228_Detrol%20LA_BioPharmr.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21-228_Detrol%20LA_BioPharmr.pdf	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

Value	Dose	Co-administered	Analyte	Population
23 μg × h/L OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21-228_Detrol%20LA_BioPharmr.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21-228_Detrol%20LA_BioPharmr.pdf	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

T_1/2

Value	Dose	Analyte	Population
8.1 h OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21-228_Detrol%20LA_BioPharmr.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21-228_Detrol%20LA_BioPharmr.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21-228_Detrol%20LA_BioPharmr.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21-228_Detrol%20LA_BioPharmr.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21-228_Detrol%20LA_BioPharmr.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21-228_Detrol%20LA_BioPharmr.pdf	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

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/12028164 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: https://pubmed.ncbi.nlm.nih.gov/12028164 Page: p.804	Disc. AE: Dry mouth... AEs leading to discontinuation/dose reduction: Dry mouth (2.4%) Sources: https://pubmed.ncbi.nlm.nih.gov/12028164 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: https://pubmed.ncbi.nlm.nih.gov/10223495 Page: p.997	unhealthy, 52 n = 58 Health Status: unhealthy Condition: Overactive bladder Age Group: 52 Sex: M+F Population Size: 58 Sources: https://pubmed.ncbi.nlm.nih.gov/10223495 Page: p.997	Disc. AE: Urinary retention... AEs leading to discontinuation/dose reduction: Urinary retention (6.9%) Sources: https://pubmed.ncbi.nlm.nih.gov/10223495 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020771s022lbl.pdf Page: p.11	unhealthy n = 986 Health Status: unhealthy Condition: Overactive bladder Sex: M+F Population Size: 986 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020771s022lbl.pdf Page: p.11	Disc. AE: Dry mouth, Dizziness... AEs leading to discontinuation/dose reduction: Dry mouth (1%) Dizziness (common) Headache (common) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020771s022lbl.pdf Page: p.11

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/12028164 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: https://pubmed.ncbi.nlm.nih.gov/12028164 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: https://pubmed.ncbi.nlm.nih.gov/10223495 Page: p.997	unhealthy, 52 n = 58 Health Status: unhealthy Condition: Overactive bladder Age Group: 52 Sex: M+F Population Size: 58 Sources: https://pubmed.ncbi.nlm.nih.gov/10223495 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020771s022lbl.pdf Page: p.11	unhealthy n = 986 Health Status: unhealthy Condition: Overactive bladder Sex: M+F Population Size: 986 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020771s022lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020771s022lbl.pdf Page: p.11	unhealthy n = 986 Health Status: unhealthy Condition: Overactive bladder Sex: M+F Population Size: 986 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020771s022lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020771s022lbl.pdf Page: p.11	unhealthy n = 986 Health Status: unhealthy Condition: Overactive bladder Sex: M+F Population Size: 986 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020771s022lbl.pdf Page: p.11

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:9622	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:9622
ChemicalBook	CB1128442	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1128442
ChemicalBook	CB4128443	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB4128443
MolPort	MolPort-002-885-868	https://www.molport.com/shop/molecule-link/MolPort-002-885-868
ZINC	ZINC000000968336	http://zinc15.docking.org/substances/ZINC000000968336
eMolecules	29542663	https://www.emolecules.com/cgi-bin/more?vid=29542663
eMolecules	902595	https://www.emolecules.com/cgi-bin/more?vid=902595

PubMed

Title	Date	PubMed
Safety profile of tolterodine as used in general practice in England: results of prescription-event monitoring.	2001	11522122
Twelve-month treatment of overactive bladder: efficacy and tolerability of tolterodine.	2001	11482747
Food does not influence the pharmacokinetics of a new extended release formulation of tolterodine for once daily treatment of patients with overactive bladder.	2001	11286323
Pharmacological characterization of muscarinic receptors in mouse isolated urinary bladder smooth muscle.	2001 Aug	11487513
Therapeutic opportunities from muscarinic receptor research.	2001 Aug	11479003
Cost-Effectiveness of tolterodine for patients with urge incontinence who discontinue initial therapy with oxybutynin: a Canadian perspective.	2001 Dec	11813937
Is extended-release oxybutynin (Ditropan XL) or tolterodine (Detrol) more effective in the treatment of an overactive bladder?	2001 Jul	11485700
Tolterodine versus oxybutynin in the treatment of urge urinary incontinence: a meta-analysis.	2001 Jul	11483904
Failure of tolterodine to treat clozapine-induced nocturnal enuresis.	2001 Jul-Aug	11485135
Urinary incontinence management: new questions from old assumptions.	2001 Jun	11454125
Effects of tolterodine, trospium chloride, and oxybutynin on the central nervous system.	2001 Jun	11402632
Food increases the bioavailability of tolterodine but not effective exposure.	2001 Mar	11269570
Cost effectiveness and quality of life considerations in the treatment of patients with overactive bladder.	2001 Mar	11261409
Overactive bladder: optimizing quality of care.	2001 Mar	11261408
Use of tolterodine in children with dysfunctional voiding: an initial report.	2001 Mar	11176516
[An example of interactions between SSRI preparations and tolterodine?].	2001 May 2	11402608
The effect of tolterodine on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive containing ethinyl estradiol and levonorgestrel.	2001 Nov	11768839
Tolterodine: an overview.	2001 Nov	11760779
Which muscarinic receptor is important in the bladder?	2001 Nov	11760777
Evidence for the efficacy and safety of tolterodine in the treatment of overactive bladder.	2001 Oct	11825311
[Continence problems after radical prostatectomy: medical treatment].	2001 Sep	11822060
Effect of tolterodine on the anticoagulant actions and pharmacokinetics of single-dose warfarin in healthy volunteers.	2002	12572529
Tolterodine: selectivity for the urinary bladder over the eye (as measured by visual accommodation) in healthy volunteers.	2002	12001821
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	12017406
Tolterodine: a safe and effective treatment for older patients with overactive bladder.	2002 Apr	11982685
Long-term health-related quality of life of patients receiving extended-release tolterodine for overactive bladder.	2002 Dec	12516956
Health-related quality of life of patients receiving extended-release tolterodine for overactive bladder.	2002 Dec	12516955
Advances in drug delivery: improved bioavailability and drug effect.	2002 Dec	12425864
Methodologic shortcomings inherent in a post-hoc analysis.	2002 Dec	12425862
Comparison of laparoscopic Burch and tension-free vaginal tape in treating stress urinary incontinence in obese patients.	2002 Jan-Mar	12002291
Gateways to clinical trials.	2002 Jul-Aug	12224444
Long-term safety, tolerability and efficacy of extended-release tolterodine in the treatment of overactive bladder.	2002 Jun	12074774
Effect of muscarinic antagonists on micturition pressure measured by cystometry in normal, conscious rats.	2002 Jun	12031395
Efficacy of botulinum-a toxin in children with detrusor hyperreflexia due to myelomeningocele: preliminary results.	2002 Mar	11880062
Tolterodine: as effective but better tolerated than oxybutynin in Asian patients with symptoms of overactive bladder.	2002 May	12060436
Efficacy, safety, and tolerability of extended-release once-daily tolterodine treatment for overactive bladder in older versus younger patients.	2002 May	12028164
Overactive bladder patients and role of the pharmacist.	2002 May-Jun	12030634
Muscarinic receptor subtypes and management of the overactive bladder.	2002 Nov	12493364
Human variability in polymorphic CYP2D6 metabolism: is the kinetic default uncertainty factor adequate?	2002 Nov	12176090
Different responses to drugs against overactive bladder in detrusor muscle of pig, guinea pig and mouse.	2002 Nov 1	12409006
The newer antimuscarinic drugs: bladder control with less dry mouth.	2002 Oct	12371799
A randomized controlled trial of tolterodine and oxybutynin on tolerability and clinical efficacy for treating Chinese women with an overactive bladder.	2002 Sep	12175392
Characterization of a new muscarinic receptor antagonist PNU-171990 in guinea pig, cat and human smooth muscle.	2002 Sep 13	12231388
New treatment options for overactive bladder and incontinence.	2002 Summer	12116753
Effects of ATP-sensitive K+ channel openers and tolterodine on involuntary bladder contractions in a pig model of partial bladder outlet obstruction.	2003	12579633
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	12581020
Simplified bladder training augments the effectiveness of tolterodine in patients with an overactive bladder.	2003 Jan	12614251

Patents

Sample Use Guides

In Vivo Use Guide

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 Dec 16 15:16:45 GMT 2023` Edited by `admin` on `Sat Dec 16 15:16:45 GMT 2023`
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 Dec 16 15:16:45 GMT 2023 , Edited by admin on Sat Dec 16 15:16:45 GMT 2023

PRIMARY

FDA UNII

75I47Y48S7

Created by admin on Sat Dec 16 15:16:45 GMT 2023 , Edited by admin on Sat Dec 16 15:16:45 GMT 2023

PRIMARY

PUBCHEM

46911937

Created by admin on Sat Dec 16 15:16:45 GMT 2023 , Edited by admin on Sat Dec 16 15:16:45 GMT 2023

PRIMARY

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TOLTERODINE

ACTIVE MOIETY

Name	Property Type	Amount	Referenced Substance	Defining	Parameters	References
Biological Half-life	PHARMACOKINETIC

Volume of Distribution	PHARMACOKINETIC

Details

SMILES

InChI

DescriptionSources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020771s022lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/16465186

CNS Activity

Approval Year

Targets

Conditions

Approved Use

Launch Date

Cmax

AUC

T1/2

Doses

AEs

Sourcing

PubMed

Patents

Sample Use Guides

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020771s022lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/16465186

C_max

T_1/2