TOLTERODINE TARTRATE

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 Search

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

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 73 Target ID: CHEMBL245 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16465186	Antagonist 1131
Muscarinic acetylcholine receptor M2 49 Target ID: CHEMBL211 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16465186	Antagonist 1131

Conditions

Condition	Modality	Targets	Highest Phase	Product
Overactive bladder 16 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020771s022lbl.pdf	Primary		Approved 4033	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

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
Fluoxetine inhibits the metabolism of tolterodine-pharmacokinetic implications and proposed clinical relevance.	1999 Oct	10583026
The overactive bladder in children: a potential future indication for tolterodine.	2001 Apr	11298060
Functional characterization of rat submaxillary gland muscarinic receptors using microphysiometry.	2001 Apr	11264256
Cost-Effectiveness of tolterodine for patients with urge incontinence who discontinue initial therapy with oxybutynin: a Canadian perspective.	2001 Dec	11813937
Pharmacokinetics of tolterodine, a muscarinic receptor antagonist, in mouse, rat and dog. Interspecies relationship comparing with human pharmacokinetics.	2001 Feb	11258043
Pharmacological characterization of muscarinic receptors in dog isolated ciliary and urinary bladder smooth muscle.	2001 Feb	11181424
Failure of tolterodine to treat clozapine-induced nocturnal enuresis.	2001 Jul-Aug	11485135
Overactive bladder: optimizing quality of care.	2001 Mar	11261408
Use of tolterodine in children with dysfunctional voiding: an initial report.	2001 Mar	11176516
The minor population of M3-receptors mediate contraction of human detrusor muscle in vitro.	2001 Oct-Dec	12123469
[Continence problems after radical prostatectomy: medical treatment].	2001 Sep	11822060
Gateways to Clinical Trials.	2002 Apr	12087878
Methodologic shortcomings inherent in a post-hoc analysis.	2002 Dec	12425862
Once-daily, extended-release formulations of antimuscarinic agents in the treatment of overactive bladder: a review.	2002 Jan	11999467
Risk of delirium with concomitant use of tolterodine and acetylcholinesterase inhibitors.	2002 Jun	12110086
Long-term safety, tolerability and efficacy of extended-release tolterodine in the treatment of overactive bladder.	2002 Jun	12074774
Muscarinic receptor antagonist-induced lenticular opacity in rats.	2002 Mar	11861984
Tolterodine: as effective but better tolerated than oxybutynin in Asian patients with symptoms of overactive bladder.	2002 May	12060436
Tolterodine-associated acute mixed liver injury.	2002 May	11978158
Assessment and conservative management of the neuropathic bladder.	2002 May	11973763
Gateways to Clinical Trials.	2002 Sep	12428432
Does gender or age affect the efficacy and safety of tolterodine?	2002 Sep	12187215
New treatment options for overactive bladder and incontinence.	2002 Summer	12116753
A new once-daily formulation of tolterodine provides superior efficacy and is well tolerated in women with overactive bladder.	2003 Feb	12601517
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

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 `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)`
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Name

Type

Language

TOLTERODINE TARTRATE

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

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