Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C22H31NO.C4H4O4 |
| Molecular Weight | 441.5598 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 1 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
OC(=O)\C=C\C(O)=O.CC(C)N(CC[C@H](C1=CC=CC=C1)C2=CC(C)=CC=C2O)C(C)C
InChI
InChIKey=HKTZTYRSKPLEIQ-BOQYJDHWSA-N
InChI=1S/C22H31NO.C4H4O4/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;5-3(6)1-2-4(7)8/h6-12,15-17,20,24H,13-14H2,1-5H3;1-2H,(H,5,6)(H,7,8)/b;2-1+/t20-;/m1./s1
| 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 | C4H4O4 |
| Molecular Weight | 116.0722 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 1 |
| 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.
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL245 |
|||
Target ID: CHEMBL211 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | DETROL Approved UseTolterodine 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 Date1998 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
3.2 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 |
|
20 μg/L |
4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered: |
TOLTERODINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
5.2 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 |
|
38 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 |
|
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 |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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: HEALTHY age: ADULT sex: MALE 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 |
|
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 |
|
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 |
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: |
unhealthy, 20-93 |
Disc. AE: Dry mouth... AEs leading to discontinuation/dose reduction: Dry mouth (2.4%) Sources: |
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: |
unhealthy, 52 |
Disc. AE: Urinary retention... AEs leading to discontinuation/dose reduction: Urinary retention (6.9%) Sources: |
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: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
Disc. AE: Dry mouth, Dizziness... AEs leading to discontinuation/dose reduction: Dry mouth (1%) Sources: Dizziness (common) Headache (common) |
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: |
unhealthy, 20-93 |
| 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: |
unhealthy, 52 |
| 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: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
| 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: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
| 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: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Clinical experiences with tolterodine. | 2001 Apr 27 |
|
| 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 |
|
| Tolterodine once-daily in treatment of the overactive bladder. | 2001 Nov |
|
| Tolterodine: a clinical review. | 2001 Oct |
|
| The minor population of M3-receptors mediate contraction of human detrusor muscle in vitro. | 2001 Oct-Dec |
|
| 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 |
|
| Gateways to Clinical Trials. | 2002 Apr |
|
| Tolterodine: a safe and effective treatment for older patients with overactive bladder. | 2002 Apr |
|
| 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 |
|
| Achieving bladder control. Treatment in the primary care setting. | 2002 May |
|
| Tolterodine and its active 5-hydroxymethyl metabolite: pure muscarinic receptor antagonists. | 2002 May |
|
| Tolterodine-associated acute mixed liver injury. | 2002 May |
|
| Assessment and conservative management of the neuropathic bladder. | 2002 May |
|
| Human variability in polymorphic CYP2D6 metabolism: is the kinetic default uncertainty factor adequate? | 2002 Nov |
|
| 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 |
|
| Treatment can lead to a long dry spell. | 2002 Spring |
|
| New treatment options for overactive bladder and incontinence. | 2002 Summer |
|
| 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 |
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
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
Edited
Wed Apr 02 08:02:17 GMT 2025
by
admin
on
Wed Apr 02 08:02:17 GMT 2025
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| Record UNII |
HH7RXJ4PW1
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| Record Status |
Validated (UNII)
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| Record Version |
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300000025701
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25119183
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615254-93-8
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HH7RXJ4PW1
Created by
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|---|---|---|---|---|
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PARENT -> SALT/SOLVATE |
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|---|---|---|---|---|
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ACTIVE MOIETY |