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Tolterodine--a new bladder-selective antimuscarinic agent
L Nilvebrant1, K E Andersson, P G Gillberg
1Medical Department Urology, Pharmacia & Upjohn AB, Uppsala, Sweden.
European Journal of Pharmacology
|May 30, 1997
Summary
Tolterodine and oxybutynin show similar antimuscarinic effects on bladder tissue. However, tolterodine exhibits greater selectivity for bladder over salivary glands in vivo, unlike oxybutynin.
Area of Science:
- Pharmacology
- Urology
Background:
- Overactive bladder and urinary urge incontinence are common conditions.
- Muscarinic receptor antagonists are a primary treatment for these conditions.
Purpose of the Study:
- To compare the in vitro and in vivo antimuscarinic properties of tolterodine and oxybutynin.
- To investigate the tissue selectivity of tolterodine and oxybutynin.
Main Methods:
- In vitro studies using isolated bladder strips from guinea pigs and humans to assess carbachol-induced contractions.
- In vivo studies in anesthetized cats to compare bladder contraction inhibition with salivation inhibition.
- Radioligand binding assays to determine affinity for various muscarinic receptor subtypes.
Main Results:
- Tolterodine demonstrated potent, competitive inhibition of bladder contractions in vitro, with affinity similar to oxybutynin.
- In vivo, tolterodine was more potent at inhibiting bladder contractions than salivation, indicating tissue selectivity.
- Oxybutynin showed the opposite tissue selectivity, with higher affinity for salivary glands compared to tolterodine.
- Binding data suggested oxybutynin has selectivity for muscarinic M3 receptors, while tolterodine's selectivity profile is less defined.
Conclusions:
- Tolterodine exhibits favorable tissue selectivity in vivo, differentiating it from oxybutynin.
- The precise mechanism for tolterodine's selectivity may involve complex interactions with muscarinic receptor subtypes or differential sensitivity of M3/m3 receptors in bladder smooth muscle versus glands.