Rupatadine Fumarate(UR-12592)

Molecular Weight (MW)	532.03
Formula	C26H26ClN3.C4H4O4
CAS No.	182349-12-8 (fumarate salt);
Storage	-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)	DMSO: 9 mg/mL (16.9 mM)
Water: <1 mg/mL
Ethanol: 13 mg/mL (24.4 mM)
Solubility (In vivo)	30% Propylene glycol, 5% Tween 80, 65% D5W: 30 mg/mL
Synonyms	Rupatadine Fumarate; UR-12592 Fumarate; UR 12592 Fumarate; UR12592 Fumarate; Pafinur; Rupax; Rupafin; Alergoliber; Rinialer; Ralif

Molecular Weight (MW)

532.03

Formula

C26H26ClN3.C4H4O4

CAS No.

182349-12-8 (fumarate salt);

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility (In vitro)

DMSO: 9 mg/mL (16.9 mM)

Water: <1 mg/mL

Ethanol: 13 mg/mL (24.4 mM)

Solubility (In vivo)

30% Propylene glycol, 5% Tween 80, 65% D5W: 30 mg/mL

Synonyms

Rupatadine Fumarate; UR-12592 Fumarate; UR 12592 Fumarate; UR12592 Fumarate; Pafinur; Rupax; Rupafin; Alergoliber; Rinialer; Ralif

In Vitro	In vitro activity: Rupatadine inhibits both platelet-activating factor (PAF) and histamine (H1) effects through its interaction with specific receptors. Rupatadine competitively inhibits histamine-induced guinea pig ileum contraction (pA2 = 9.29 ± 0.06) without affecting contraction induced by ACh, serotonin or leukotriene D4(LTD4). It also competitively inhibits PAF-induced platelet aggregation in washed rabbit platelets (WRP) (pA2= 6.68 ± 0.08) and in human platelet-rich plasma (HPRP) (IC50 = 0.68 μM), while not affecting ADP- or arachidonic acid-induced platelet aggregation. In another study, it is reported rupatadine and loratadine shows similar inhibitory effect on histamine and TNF-α release, whereas SR-27417A only exhibits inhibitory effect against TNF-α. Kinase Assay: Antagonists are incubated with guinea pig cerebellum membranes (0.6 mg/ml) and [3H]-pyrilamine (1.2 nM) in 0.5 ml 50 mM PBS, pH 7.5, for 30 min at 25 ℃. The incubation is ended by the addition of 5 ml of ice-cold PBS containing 2 μM pyrilamine and the collection of membranes on Whatman GF/B filters. Then the filters are washed with 3 × 5 ml of ice-cold PBS plus 2 μM pyrilamine and transferred to counting vials. The radioactivity retained by each filter is measured by liquid scintillation counting in 3 ml of HiSafe 3. Specific binding is determined from the difference between the [3H]-pyrilamine bound in the absence and in the presence of a large molar excess (10 μM) of unlabeled promethazine. Cell Assay: Platelet aggregation is induced by C18-PAF and measured by using a dual-channel aggregometer Chrono-log 560. Platelet aggregation in the absence and in the presence (5-min incubation) of the test compounds is recorded. Activity of the inhibitors is expressed as the IC50 values. To assess selectivity, rupatadine is tested against other aggregating agents, including arachidonic acid (1 mM) and ADP (5 μM), in WRP. Dose-response curves for PAF-induced aggregation in WRP are obtained in the absence of rupatadine and in its presence at various concentrations (3 × 10-7–3 × 10-5 M).
In Vivo	Rupatadine blocks histamine- and PAF-induced effects in vivo, such as hypotension in rats (ID50 = 1.4 and 0.44 mg/kg i.v., respectively) and bronchoconstriction in guinea pigs (ID50 = 113 and 9.6 μg/kg i.v.). Moreover, it potently inhibits PAF-induced mortality in mice (ID50 = 0.31 and 3.0 mg/kg i.v. and p.o., respectively) and endotoxin-induced mortality in mice and rats (ID50 = 1.6 and 0.66 mg/kg i.v.). Rupatadine's duration of action is long, as assessed by the histamine- and PAF-induced increase in vascular permeability test in dogs (42 and 34% inhibition at 26 h after 1 mg/kg p.o.). Rupatadine at a dose of 100 mg/kg p.o. neither modifies spontaneous motor activity nor prolongs barbiturate-sleeping time in mice, which indicates a lack of sedative effects.
Animal model	PAF- and histamine-induced hypotension in normotensive rats
Formulation & Dosage	Dissolved in saline; 1 mg/kg; i.v. injection
References	J Pharmacol Exp Ther. 1997 Jan;280(1):114-21; J Pharmacol Exp Ther. 1997 Jan;280(1):114-21.

In Vitro

In vitro activity: Rupatadine inhibits both platelet-activating factor (PAF) and histamine (H1) effects through its interaction with specific receptors. Rupatadine competitively inhibits histamine-induced guinea pig ileum contraction (pA2 = 9.29 ± 0.06) without affecting contraction induced by ACh, serotonin or leukotriene D4(LTD4). It also competitively inhibits PAF-induced platelet aggregation in washed rabbit platelets (WRP) (pA2= 6.68 ± 0.08) and in human platelet-rich plasma (HPRP) (IC50 = 0.68 μM), while not affecting ADP- or arachidonic acid-induced platelet aggregation. In another study, it is reported rupatadine and loratadine shows similar inhibitory effect on histamine and TNF-α release, whereas SR-27417A only exhibits inhibitory effect against TNF-α.

Kinase Assay: Antagonists are incubated with guinea pig cerebellum membranes (0.6 mg/ml) and [3H]-pyrilamine (1.2 nM) in 0.5 ml 50 mM PBS, pH 7.5, for 30 min at 25 ℃. The incubation is ended by the addition of 5 ml of ice-cold PBS containing 2 μM pyrilamine and the collection of membranes on Whatman GF/B filters. Then the filters are washed with 3 × 5 ml of ice-cold PBS plus 2 μM pyrilamine and transferred to counting vials. The radioactivity retained by each filter is measured by liquid scintillation counting in 3 ml of HiSafe 3. Specific binding is determined from the difference between the [3H]-pyrilamine bound in the absence and in the presence of a large molar excess (10 μM) of unlabeled promethazine.

Cell Assay: Platelet aggregation is induced by C18-PAF and measured by using a dual-channel aggregometer Chrono-log 560. Platelet aggregation in the absence and in the presence (5-min incubation) of the test compounds is recorded. Activity of the inhibitors is expressed as the IC50 values. To assess selectivity, rupatadine is tested against other aggregating agents, including arachidonic acid (1 mM) and ADP (5 μM), in WRP. Dose-response curves for PAF-induced aggregation in WRP are obtained in the absence of rupatadine and in its presence at various concentrations (3 × 10-7–3 × 10-5 M).

In Vivo

Rupatadine blocks histamine- and PAF-induced effects in vivo, such as hypotension in rats (ID50 = 1.4 and 0.44 mg/kg i.v., respectively) and bronchoconstriction in guinea pigs (ID50 = 113 and 9.6 μg/kg i.v.). Moreover, it potently inhibits PAF-induced mortality in mice (ID50 = 0.31 and 3.0 mg/kg i.v. and p.o., respectively) and endotoxin-induced mortality in mice and rats (ID50 = 1.6 and 0.66 mg/kg i.v.). Rupatadine's duration of action is long, as assessed by the histamine- and PAF-induced increase in vascular permeability test in dogs (42 and 34% inhibition at 26 h after 1 mg/kg p.o.). Rupatadine at a dose of 100 mg/kg p.o. neither modifies spontaneous motor activity nor prolongs barbiturate-sleeping time in mice, which indicates a lack of sedative effects.

Animal model

PAF- and histamine-induced hypotension in normotensive rats

Formulation & Dosage

Dissolved in saline; 1 mg/kg; i.v. injection

References

J Pharmacol Exp Ther. 1997 Jan;280(1):114-21; J Pharmacol Exp Ther. 1997 Jan;280(1):114-21.

CAS NO:	182349-12-8
规格:	≥98%

包装	价格(元)
100mg	电议
250mg	电议
500mg	电议
1g	电议
2g	电议