In vitro activity: Flavoxate displaces [3H]nitrendipine on the Ca2+ channels binding sites with IC50 of 254 μM. Flavoxate (>10 μM) suppresses carbachol-induced contractions in isolated rat detrusor strips with pD value of 4.55. Flavoxate (>10 μM) suppresses Ca2+-induced contractions in isolated rat detrusor strips with pIC50 value of 4.92. Flavoxate (0.01 μM −10 μM) inhibits CAMP formation in a concentration-dependent manner in membranes from the rat striatum and cerebral cortex, an action which is completely abolished by pretreating the membranes with pertussis toxin (PTX). Flavoxate causes a concentration-dependent reduction of the K+-induced contraction of human urinary bladder. Flavoxate inhibits the peak amplitude of voltage-dependent nifedipine-sensitive inward Ba2+ currents in a voltage- and concentration-dependent manner with Ki value of 10 μM in human detrusor myocytes.

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In isolated rat detrusor strips, Flavoxate HCl at concentrations higher than 10^-5 mol/L produced a downward shift of the carbachol-induced concentration-response curve, with a pD2' value of 4.55 (noncompetitive antagonism).[1]
In isolated rat detrusor strips, Flavoxate HCl at concentrations higher than 10^-5 mol/L suppressed Ca2+-induced contractions, with a pIC50 value of 4.92 for inhibiting the response induced by 5 mmol/L CaCl2.[1]

Flavoxate (10mg/kg) suppresses both the an initial, rapidly rising phasic contraction (phase 1) and the tonic contraction (phase 2) contractions to the same extent in rats. Flavoxate (10mg/kg) abolishes the bladder contractions without causing any change in the amplitude of the contractions in rats. Flavoxate (3 mg/kg) abolishes the efferent neural activity and the associated bladder contractions for about 10 minutes without changing the baseline vesical pressure in rats. ICV-injected (50 to 200 μg/rat) or IT-injected (100 to 200 μg/rat) Flavoxate abolishes rhythmic bladder contractions during and after injection for five to 15 minutes in a dose-dependent manner in rats. Flavoxate (3 mg/kg, i.v.) abolishes rhythmic bladder contractions and the maximal intervals of voiding contractions is 7.20 min.

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In anesthetized rats, intravenous Flavoxate HCl at doses ≥10 mg/kg suppressed both the initial phasic (phase 1) and later tonic (phase 2) bladder contractions induced by electrical stimulation of the distal end of the pelvic nerve.[1]
In anesthetized rats, intravenous Flavoxate HCl at doses ≥3 mg/kg abolished isovolumetric rhythmic bladder contractions without changing baseline vesical pressure or afferent pelvic nerve activity.[1]
In anesthetized rats, intravenous Flavoxate HCl at 3 mg/kg abolished efferent pelvic nerve activity associated with rhythmic bladder contractions for about 10 minutes without changing baseline vesical pressure.[1]
In anesthetized rats, intracerebroventricular (ICV) injection of Flavoxate HCl (50 to 200 μg/rat) or intrathecal (IT) injection (100 to 200 μg/rat) abolished isovolumetric rhythmic bladder contractions in a dose-dependent manner for 5 to 15 minutes.[1]
In decerebrated cats, microinjection of Flavoxate HCl (0.68 μg in 0.2 μL of 0.34% solution) into the nucleus reticularis pontis oralis (PoO) significantly increased the threshold bladder capacity to produce reflex micturition (from 15.64±2.52 mL to 19.22±2.71 mL) and increased voiding volume (from 15.60±2.54 mL to 18.50±2.55 mL), without affecting maximal bladder pressure or residual volume, and reduced external urethral sphincter EMG activity. Microinjection into the locus coeruleus alpha (LCα) or locus subcoeruleus (LSC) produced no significant changes.[1]

Dissolved in saline; 10 mg/kg; i.v. injection Sprague-Dawley rats

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For in vitro experiments using isolated rat detrusor strips: Male rats (250-450g) were killed under deep ether anesthesia, bladders removed, and longitudinal detrusor strips (5 mm length, 2 mm width) mounted under 1 g resting tension in Krebs solution (37°C, 5% CO2/95% O2) for at least 60 min. Carbachol concentration-response curves were obtained in the presence of 3 μmol/L phentolamine and 1 μmol/L propranolol. For Ca2+-induced contractions, the bath solution was changed to Ca2+-free, high-K+ Krebs solution (100 mmol/L KCl), equilibrated for ≥60 min, then CaCl2 was applied cumulatively.[1]
For electrically stimulated bladder contractions in rats: Female rats (170-250g) were anesthetized with urethane (900 mg/kg, subcutaneous). Bilateral ureters cannulated with PE-10 tubing, bladder cannulated via dome with PE-60 for intravesical pressure measurement and saline infusion. Intravesical pressure maintained at 50% threshold capacity. Bilateral pelvic nerves sectioned 3 mm proximal to bladder, distal stump placed on bipolar platinum electrode and stimulated at supramaximal voltage (8-10 V, 1 ms, 5 Hz) for 60 seconds. Femoral artery cannulated for blood pressure monitoring.[1]
For isovolumetric rhythmic bladder contractions in rats: Bladder cannulated via urethra with PE-60, secured by ligature, connected to pressure transducer and infusion pump. Bladder filled with 0.1 mL increments of warm saline (37°C) until rhythmic contractions occurred at constant intervals for 15 min, then test drugs injected intravenously.[1]
For afferent/efferent pelvic nerve activity recording in rats: Intravesical pressure maintained at 10-15 cm H2O. Bilateral hypogastric and pelvic nerves sectioned 10 mm proximal to pelvic nerve plexus, distal stump (for afferent) or proximal stump of preganglionic fibers (for efferent) placed on bipolar platinum electrodes. Neural activity amplified, spikes selected with window discriminator, firing rate measured over 20-second (afferent) or 2-second (efferent) intervals.[1]
For intracerebroventricular injection in rats: After inducing isovolumetric rhythmic contractions, rat placed in stereotaxic instrument, craniotomy performed, guide cannula introduced into lateral ventricle. When contractions constant, injection cannula inserted and Flavoxate HCl injected ICV at 2 μL/min via microinjection pump.[1]
For intrathecal injection in rats: Midline dorsal incision made, stainless steel needle attached to polyethylene tubing inserted into subarachnoid space between L-5 and L-6, Flavoxate HCl (2-8 μL) manually injected IT with microsyringe.[1]
For microinjection into lateral pontine tegmentum in decerebrated cats: Male/female cats (2.5-4.5 kg) anesthetized with ketamine (15 mg/kg IM), trachea intubated, anesthesia maintained with enflurane and N2O. Double lumen catheter introduced into bladder via dome for pressure recording and saline infusion. Cat placed in standing position in stereotaxic instrument, decerebrated at supra-collicular-post mammillary level. Bipolar electrode placed in external urethral sphincter for EMG. Reflex micturition induced by bladder filling with saline. Micro glass pipette (tip 30 μm) filled with 0.34% Flavoxate HCl solution stereotaxically introduced into LCα, LSC, or PoO, and 0.2 μL injected over 2 seconds. Cystometrogram and EMG recorded immediately after injection.[1]

In rats and dogs, after intravenous injection of radiolabeled Flavoxate HCl ([14C]flavoxate) at 6.7 mg/kg, the concentration of total radioactivity in the whole brain was about 10 μg equivalents to flavoxate per gram at 5 minutes post-injection. An autoradiographic study demonstrated significant radioactivity throughout the brain 5 minutes after intravenous injection.[1]

Int J Urol.1996 May;3(3):218-27;Brain Res.1996 Jul 15;727(1-2):91-8.

Flavonoid hydrochloride is the hydrochloride salt of flavonoid hydrochloride. It is a muscarinic receptor antagonist, antispasmodic agent, and parasympathetic blocker. It contains the flavonoid (1+) ion. Flavonoid hydrochloride is the hydrochloride form of flavonoid hydrochloride, a parasympathetic blocker with antispasmodic effects. Flavonoid hydrochloride competitively binds to muscarinic receptors, thereby blocking the action of acetylcholine. This relaxes vascular smooth muscle (primarily urinary tract smooth muscle) and inhibits smooth muscle contraction. This drug has been used to treat various urinary tract diseases and as an antispasmodic agent. Its therapeutic uses and mechanism of action are not yet fully understood. It may have local anesthetic activity, a direct relaxant effect on smooth muscle, and some muscarinic antagonistic activity. See also: Flavonoid hydrochloride (with active ingredient).

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Flavoxate HCl suppressed the micturition reflex primarily by facilitating the inhibitory action of the nucleus reticularis pontis oralis (PoO) on the descending pathways from the pontine micturition center (LCα) to the sacral parasympathetic intermediolateral nuclei.[1]
The Ca2+ antagonistic potency of Flavoxate HCl was approximately 1/300 that of verapamil in isolated rat detrusor strips (pIC50 4.92 vs 7.41 for verapamil).[1]
In contrast to verapamil (which acts on bladder smooth muscle/afferent pathway) and atropine (which acts on efferent pathway/parasympathetic neuroeffector junction), the sites of action of Flavoxate HCl are in the descending pathway including the dorsolateral portion of the pontine tegmentum and parasympathetic intermediolateral sacral nuclei.[1]

C24H25NO4.HCL

427.92

427.155

3717-88-2

Flavoxate;15301-69-6;Flavoxate-d4 hydrochloride;1189678-43-0

441345

White to off-white solid powder

1.203g/cm3

564.1ºC at 760 mmHg

232-234°C

294.9ºC

5.151

1

5

6

30

631

0

XOEVKNFZUQEERE-UHFFFAOYSA-N

InChI=1S/C24H25NO4.ClH/c1-17-21(26)19-11-8-12-20(23(19)29-22(17)18-9-4-2-5-10-18)24(27)28-16-15-25-13-6-3-7-14-25;/h2,4-5,8-12H,3,6-7,13-16H2,1H3;1H

2-piperidin-1-ylethyl 3-methyl-4-oxo-2-phenylchromene-8-carboxylate;hydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)