solifenacin

Names

[ Name ]:
solifenacin

[Synonym ]:
T66 CNT&J BR& CVO- AT66 A B CNTJ &&(1S)-(3R)- Form
(1S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate
solifenacin
2(1H)-Isoquinolinecarboxylic acid, 3,4-dihydro-1-phenyl-, (3R)-1-azabicyclo[2.2.2]oct-3-yl ester, (1S)-
(1S)-3,4-dihydro-1-phenyl-2(1H)-isoquinolinecarboxylic acid (3R)-1-azabicyclo[2.2.2]oct-3-yl ester
2(1H)-Isoquinolinecarboxylic acid, 3,4-dihydro-1-phenyl-, 1-azabicyclo[2.2.2]oct-3-yl ester, (1S)-
[(8R)-1-azabicyclo[2.2.2]octan-8-yl] (1S)-1-phenyl-3,4-dihydro-1H-isoquinoline-2-carboxylate
(+)-solifenacin
1-Azabicyclo[2.2.2]oct-3-yl (1S)-1-phenyl-3,4-dihydro-2(1H)-isoquinolinecarboxylate
(3R)-1-Azabicyclo[2.2.2]oct-3-yl (1S)-1-phenyl-3,4-dihydro-2(1H)-isoquinolinecarboxylate
(1S)-(3R)-1-azabicyclo[2,2,2]oct-3-yl-3,4-dihydro-1-phenyl-2(1H)-isoquinoline carboxylate
YM 905
(3R)-1-Azabicyclo[2.2.2]oct-3-yl (1S)-3,4-dihydro-1-phenyl-2(1H)-Isoquinolinecarboxylate
Unii-A8910sqj1u
Vesicare
3,4-dihydro-1-phenyl-(1S)-2(1H)-Isoquinolinecarboxylic acid (3R)-1-azabicyclo[2.2.2]oct-3-yl ester
2(1H)-Isoquinolinecarboxylic acid,3,4-dihydro-1-phenyl-,1-azabicyclo(2.2.2)oct-3-yl ester,(R-(R*,S*))
(1S,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

Biological Activity

[Description]:

Solifenacin is a novel muscarinic receptor antagonist with pKis of 7.6, 6.9 and 8.0 for M1, M2 and M3 receptors, respectively.

[Related Catalog]:

Signaling Pathways >> GPCR/G Protein >> mAChR

Signaling Pathways >> Neuronal Signaling >> mAChR

Research Areas >> Neurological Disease

[Target]

pKi: 7.6 (M1 receptor), 6.9 (M2 receptor), 8.0 (M3 receptor)[1]

[In Vitro]

Solifenacin is a novel muscarinic receptor antagonist with pKis of 7.6±0.056, 6.9±0.034 and 8.0±0.021 for M1, M2 and M3 receptors, respectively. In murine submandibular gland cells, the antagonistic effects of 100 nM Solifenacin and oxybutynin on Ca2+ mobilization evoked by varying doses of carbachol (CCh) are examined. Solifenacin does not shift the CCh dose-activation curve in a parallel manner whereas oxybutynin shows insurmountable antagonism. The pKb values are obtained as 7.4±0.17 for Solifenacin and 8.8±0.21 for oxybutynin[1].

[In Vivo]

Solifenacin reduces bladder responses by 40% at a dose of 210 nmol/kg (0.1 mg/kg) and abolishes them at 2100 nmol/kg (1 mg/kg). In contrast, its inhibitory effects on salivary and cardiac responses are only slight at 630 nmol/kg (0.3 mg/kg), and reach 66% and 49%, respectively, at 2100 nmol/kg (1 mg/kg). At doses of 63 and 210 nmol/kg (0.03 and 0.1 mg/kg), Solifenacin slightly increases saliva secretion[1]. Solifenacin (0.01 to 0.3 mg/kg i.v.) dose-dependently increases bladder capacity and voided volume at doses of 0.03 mg/kg i.v. or more, but does not affect residual volume or micturition pressure at any dose tested[2].

[Cell Assay]

Cytosolic Ca2+ mobilization is determined in guinea pig detrusor cells. Briefly, single detrusor cells are prepared from epithelium-free bladders, loaded with Fura 2, and suspended in phenol red-free Hanks’ balanced salt solution supplemented with 20 mM HEPES (pH=7.4) and 0.1% bovine serum albumin (HBSS-H/B). A 490 μL aliquot of the cell suspension is continuously stirred, kept at 28°C and monitored for the ratio of fluorescence at 500 nm with excitation at 340 nm to that at 380 nm. To each aliquot, 5 μL of test drug (including Solifenacin) and stimulant solutions are serially added with a 2 min interval, and the peak increase over the level just before stimulation is used for data analysis[1].

[Animal admin]

Male rats (270 to 320 g) are used in this study. After the measurement of neurological deficits, cystometry is performed. Briefly, conscious rats showing a moderate to severe neurological deficit (score: 4 to13) are placed in a restraining cage. To facilitate drug (including Solifenacin) evaluation, only those animals showing urinary frequency are eligible for study. The bladder is emptied by drainage of urine through the catheter and then continuously re-infused with saline. After stable voiding cycles are established, each rat receives a single intravenous administration of test drug (including Solifenacin) at a volume of 1 ml/kg[2].

[References]

[1]. Ikeda K, et al. M(3) receptor antagonism by the novel antimuscarinic agent solifenacin in the urinary bladder and salivary gland. Naunyn Schmiedebergs Arch Pharmacol. 2002 Aug;366(2):97-103.

[2]. Suzuki M, et al. Effects of solifenacin succinate (YM905) on detrusor overactivity in conscious cerebral infarctedrats. Eur J Pharmacol. 2005 Apr 4;512(1):61-6.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
505.5±50.0 °C at 760 mmHg

[ Molecular Formula ]:
C₂₃H₂₆N₂O₂

[ Molecular Weight ]:
362.465

[ Flash Point ]:
259.5±30.1 °C

[ Exact Mass ]:
362.199432

[ PSA ]:
32.78000

[ LogP ]:
3.70

[ Vapour Pressure ]:
0.0±1.3 mmHg at 25°C

[ Index of Refraction ]:
1.649

solifenacin

Names

Biological Activity

Chemical & Physical Properties

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Related Compounds