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=C(O)C=CC(C)=C2)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 |
|---|---|---|---|---|
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
| 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 |
|---|---|---|---|---|
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
| 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: 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%) Sources: Page: p.11Dizziness (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: 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
| Title | Date | PubMed |
|---|---|---|
| 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 |
|
| Is extended-release oxybutynin (Ditropan XL) or tolterodine (Detrol) more effective in the treatment of an overactive bladder? | 2001 Jul |
|
| Tolterodine versus oxybutynin in the treatment of urge urinary incontinence: a meta-analysis. | 2001 Jul |
|
| Failure of tolterodine to treat clozapine-induced nocturnal enuresis. | 2001 Jul-Aug |
|
| The effect of tolterodine on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive containing ethinyl estradiol and levonorgestrel. | 2001 Nov |
|
| Tolterodine: an overview. | 2001 Nov |
|
| Which muscarinic receptor is important in the bladder? | 2001 Nov |
|
| Tolterodine once-daily in treatment of the overactive bladder. | 2001 Nov |
|
| Medical treatment of overactive bladder. | 2001 Nov |
|
| 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 |
|
| Anticholinergic drugs versus placebo for overactive bladder syndrome in adults. | 2002 |
|
| Gateways to Clinical Trials. | 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 |
|
| 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 |
|
| Current pharmacotherapeutic strategies for overactive bladder. | 2002 Jul |
|
| Gateways to clinical trials. | 2002 Jul-Aug |
|
| Risk of delirium with concomitant use of tolterodine and acetylcholinesterase inhibitors. | 2002 Jun |
|
| Long-term safety, tolerability and efficacy of extended-release tolterodine in the treatment of overactive bladder. | 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 |
|
| Achieving bladder control. Treatment in the primary care setting. | 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 |
|
| Overactive bladder patients and role of the pharmacist. | 2002 May-Jun |
|
| Muscarinic receptor subtypes and management of the overactive bladder. | 2002 Nov |
|
| Functional role of central muscarinic receptors for micturition in normal conscious rats. | 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 |
|
| 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 |
|
| 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 |
|
| 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 |
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
Sat Dec 16 16:34:11 GMT 2023
by
admin
on
Sat Dec 16 16:34:11 GMT 2023
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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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HH7RXJ4PW1
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