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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Pharmacological characterization of a new antimuscarinic agent, solifenacin succinate, in comparison with other antimuscarinic agents.

Solifenacin succinate [YM905; (3R)-1-azabicyclo[2.2.2]oct-3-yl(1S)-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxylate monosuccinate] is a new muscarinic receptor antagonist developed for the treatment of overactive bladder. The aim of the present study was to evaluate the antimuscarinic properties of solifenacin and to compare the results with those obtained for tolterodine, oxybutynin, darifenacin, propiverine and atropine. In radioligand receptor binding assay, K(i) values of solifenacin for human muscarinic M(1), M(2), M(3), M(4) and M(5) receptors were 26, 170, 12, 110 and 31 nM, respectively. In isolated rat urinary bladder, solifenacin competitively antagonized carbachol-induced contractions, with a pA(2) value of 7.44+/-0.09. In these in vitro studies, the antimuscarinic action of solifenacin was more potent than that of propiverine and less potent than those of tolterodine, oxybutynin, darifenacin and atropine. In anesthetized rats, solifenacin and oxybutynin increased the maximum bladder capacity in a dose-dependent manner and also decreased the maximum intravesical pressure. The dosages required to produce a 30% increase in maximum bladder capacity (ED(30) values) of solifenacin and oxybutynin were 0.35 and 0.30 mg/kg i.v., respectively, indicating approximately equal efficacies. These results support the fact that solifenacin, similarly to currently used antimuscarinic agents, is an effective agent in the treatment of overactive bladder symptoms such as urinary frequency and urge incontinence.[1]

References

  1. Pharmacological characterization of a new antimuscarinic agent, solifenacin succinate, in comparison with other antimuscarinic agents. Ohtake, A., Saitoh, C., Yuyama, H., Ukai, M., Okutsu, H., Noguchi, Y., Hatanaka, T., Suzuki, M., Sato, S., Sasamata, M., Miyata, K. Biol. Pharm. Bull. (2007) [Pubmed]
 
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