208993-54-8
208993-54-8 structure
- Name: Fiduxosin
- Chemical Name: 3-[4-[(3aR,9bR)-9-methoxy-3,3a,4,9b-tetrahydro-1H-chromeno[3,4-c]pyrrol-2-yl]butyl]-8-phenyl-1H-pyrazino[1,2]thieno[3,4-b]pyrimidine-2,4-dione
- CAS Number: 208993-54-8
- Molecular Formula: C30H29N5O4S
- Molecular Weight: 555.64700
- Catalog: Signaling Pathways GPCR/G Protein Adrenergic Receptor
- Create Date: 2017-10-16 11:37:49
- Modify Date: 2024-01-10 07:43:00
-
Fiduxosin is a potent α1-adrenoceptor antagonist, with Ki of 0.160 nM, 24.9 nM, and 0.920 nM for α1a-, α1b-, and α1d-adrenoceptors, respectively.
| Name | 3-[4-[(3aR,9bR)-9-methoxy-3,3a,4,9b-tetrahydro-1H-chromeno[3,4-c]pyrrol-2-yl]butyl]-8-phenyl-1H-pyrazino[1,2]thieno[3,4-b]pyrimidine-2,4-dione |
|---|---|
| Synonyms |
UNII-W9O92HYT6I
Fiduxosin [INN] Fiduxosin |
| Description | Fiduxosin is a potent α1-adrenoceptor antagonist, with Ki of 0.160 nM, 24.9 nM, and 0.920 nM for α1a-, α1b-, and α1d-adrenoceptors, respectively. |
|---|---|
| Related Catalog | |
| Target |
Ki: 0.16 nM (α1a-adrenoceptor), 24.9 nM (α1b- adrenoceptor), 0.92 nM (α1d-adrenoceptor), 92 nM (Human α2a-adrenoceptor), 22 nM (Human α2c-adrenoceptor), 21 nM (Rat α2b-adrenoceptor), 29 nM (Rat 5HT1A receptor)[1] |
| In Vitro | Fiduxosin displays low affinity for other adrenoceptors, including cloned human α2a- (92 nM) and α2c-adrenoceptors (22 nM) and rat neonatal lung α2b-adrenoceptors (21 nM), in addition to β-adrenoceptors (2-5 μM). Fiduxosin also has low affinity for 5HT1A receptors in rat cortex (29 nM) compared with its affinity at α1a-adrenoceptors (0.16 nM). Fiduxosin antagonizes competitively PE-induced responses with a pA2 value of 7.58, in the rabbit urethra[1]. |
| In Vivo | Fiduxosin (30, 100, and 300 μg/kg, i.v.) antagonizes IUP responses to i.v. EPI in anesthetized dogs. Fiduxosin (178, 592, and 1780 μg/kg, i.v.) elicits transient effects on blood pressure, with no effect of the lowest dose on MAP in spontaneously hypertensive rats (SHR). Fiduxosin (3 μmol/kg or 1780 μg/kg i.v.) slightly reduces MAP, but head-up tilt causes further diminution of MAP at only the 15-min observation with minimal additional changes in MAP at times ≥30 min postdosing in SHR[1]. Fiduxosin (0.1, 0.3, 1.0, and 3.0 mg/kg p.o.) blocks prostatic intraurethral pressure (IUP) responses to a greater extent than MAP responses. The IUP ED50 values of fiduxosin is 0.24 mg/kg[2]. |
| Animal Admin | Male beagle dogs (>2 years old, 12-15 kg) are chronically instrumented for the continuous measurement of arterial blood pressure by implanting a telemetry transducer/transmitter (TA11PA-C40) into a carotid artery. On test day, dogs are placed in sling restraints and an Abbocath-T i.v. catheter (18-G) is inserted into a cephalic vein for blood sampling and for the administration of agonist. Prostatic intraurethral pressure (IUP) is measured using a transurethral 7F Swan-Ganz balloon catheter (41224-01). Dose responses of the intraurethral and arterial pressor effects of 8, 16, and 32 μg/kg i.v. phenylephrine (PE) are obtained before and at various time points after a single p.o. dose of an antagonist. Fiduxosin is dissolved in a vehicle of 20% ethanol, 30% propylene glycol, and 50% water. Terazosin and tamsulosin are dissolved in water. All antagonists are given by gavage in a volume of 1 mL/kg. PE is dissolved in saline and administered in a volume of 0.1 mL/kg. The increase in IUP or mean arterial pressure (MAP) caused by PE is allowed to return to baseline before the next dose is administered. |
| References |
| Molecular Formula | C30H29N5O4S |
|---|---|
| Molecular Weight | 555.64700 |
| Exact Mass | 555.19400 |
| PSA | 130.84000 |
| LogP | 4.60850 |