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Details

Stereochemistry ABSOLUTE
Molecular Formula C22H31NO
Molecular Weight 325.4876
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TOLTERODINE

SMILES

CC(C)N(CC[C@H](C1=CC=CC=C1)C2=CC(C)=CC=C2O)C(C)C

InChI

InChIKey=OOGJQPCLVADCPB-HXUWFJFHSA-N
InChI=1S/C22H31NO/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/t20-/m1/s1

HIDE SMILES / InChI

Description

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 TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
DETROL

Cmax

ValueDoseCo-administeredAnalytePopulation
3.2 μg/L
4 mg single, oral
TOLTERODINE plasma
Homo sapiens
20 μg/L
4 mg single, oral
TOLTERODINE plasma
Homo sapiens
5.2 μg/L
4 mg 2 times / day multiple, oral
TOLTERODINE plasma
Homo sapiens
38 μg/L
4 mg 2 times / day multiple, oral
TOLTERODINE plasma
Homo sapiens
1.8 μg/L
8 mg single, oral
TOLTERODINE plasma
Homo sapiens
2.3 μg/L
8 mg single, oral
TOLTERODINE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
23 μg × h/L
8 mg single, oral
TOLTERODINE plasma
Homo sapiens
27 μg × h/L
8 mg single, oral
TOLTERODINE plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
2 h
4 mg single, oral
TOLTERODINE plasma
Homo sapiens
6.5 h
4 mg single, oral
TOLTERODINE plasma
Homo sapiens
2.2 h
4 mg 2 times / day multiple, oral
TOLTERODINE plasma
Homo sapiens
9.6 h
4 mg 2 times / day multiple, oral
TOLTERODINE plasma
Homo sapiens
8.1 h
8 mg single, oral
TOLTERODINE plasma
Homo sapiens
7.9 h
8 mg single, oral
TOLTERODINE plasma
Homo sapiens

Doses

AEs

PubMed

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.