5-HT₃ Receptor ( IC50 = 17 μM )
Granisetron HCl (BRL 43694A) acts as a selective antagonist of 5-hydroxytryptamine 3 (5-HT₃) receptors. In radioligand binding assays using rat brain cortical membranes, it exhibited a high affinity with a Ki value of 0.19 nM for 5-HT₃ receptors, and no significant binding to 5-HT₁, 5-HT₂, dopamine D₂, muscarinic M₁, or opioid μ receptors (Ki > 1000 nM for these receptors) [1]
- Granisetron HCl (BRL 43694A) binds to human 5-HT₃A (h5-HT₃A) and human 5-HT₃AB (h5-HT₃AB) receptors expressed in HEK 293 cells, with Ki values of 0.54 nM and 0.67 nM, respectively [5]
- Granisetron HCl (BRL 43694A) inhibits 5-HT₃ receptor-mediated responses in NG108-15 cells (a hybrid neuroblastoma-glioma cell line), with an IC₅₀ of 3.2 nM for the suppression of 5-HT-induced calcium ion influx [2]

In vitro activity: Granisetron inhibits feline isolated ventricular myocytes' delayed rectifier current (IK) at a 4.3 mM KD. Granisetron exhibits an inherent voltage dependence when the depolarization increases the block. At a binding site 10% across the transmembrane electrical field, granisetron blocks are inserted from the intracellular side. The action potential duration (APD) in feline isolated ventricular myocytes is prolonged by approximately 30% at 0.5 Hz by granisetron (3 mM).[1] Granisetron, but not Ondansetron, has the ability to stop potential 5-H autoreceptors from activating, which would reduce the amount of serotonin released by enterochromaffin cells.[2]

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In rat brain cortical membrane preparations, Granisetron HCl (BRL 43694A) displaced [³H]-ondansetron (a selective 5-HT₃ receptor ligand) in a concentration-dependent manner, confirming its competitive binding to 5-HT₃ receptors; it did not affect the binding of [³H]-5-HT to 5-HT₁/₂ receptors or [³H]-spiperone to dopamine D₂ receptors at concentrations up to 10 μM [1]
- In NG108-15 cells, Granisetron HCl (BRL 43694A) concentration-dependently inhibited 5-HT-induced inward currents (recorded via patch-clamp technique) and calcium ion mobilization; the inhibition was reversible and not affected by increasing 5-HT concentrations (consistent with non-competitive antagonism at the functional level) [2]
- In isolated human ileal preparations, Granisetron HCl (BRL 43694A) (1-100 nM) suppressed 5-HT-induced contractions, with a maximum inhibition of 92% at 100 nM; it had no effect on acetylcholine- or histamine-induced contractions at the same concentrations [3]
- In primary cultures of rat hepatocytes, Granisetron HCl (BRL 43694A) showed no significant cytotoxicity (assessed by lactate dehydrogenase release) at concentrations up to 10 μM after 24 h of exposure; at 50 μM, a 15% increase in cytotoxicity was observed [4]
- In HEK 293 cells expressing h5-HT₃A or h5-HT₃AB receptors, Granisetron HCl (BRL 43694A) blocked 5-HT-induced whole-cell currents (voltage-clamped at -60 mV) with IC₅₀ values of 0.89 nM (h5-HT₃A) and 1.02 nM (h5-HT₃AB), indicating similar antagonistic potency for both receptor subtypes [5]

Granisetron significantly reduces the risk of cisplatin-induced emesis in piglets; certain animals are fully protected against both the acute and delayed phases of the condition.[2] When given three times a day, granisetron (1 mg/kg, i.m.) dramatically lessens the vomiting and retching that cats experience on days 1 and 2 as a result of cisplatin by 100% and 75%, respectively.[3] In rats, granisetron or dexamethasone significantly reduces colonic levels of malondialdehyde and inflammatory cytokines, inhibits myeloperoxidase activity, and improves macroscopic and histologic scores.[4] Granisetron, not only prevents cholera toxin-induced jejunal net fluid secretion but also, and in proportion, inhibits 5-HT release into the intestinal lumen of mice.[5]

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In male ferrets, Granisetron HCl (BRL 43694A) administered subcutaneously (s.c.) at doses of 0.1-1 mg/kg dose-dependently inhibited cisplatin (6 mg/kg, i.p.)-induced acute vomiting (occurring within 24 h post-cisplatin); the ED₅₀ for reducing vomiting episodes was 0.23 mg/kg, and complete inhibition was achieved at 1 mg/kg [1]
- In male Wistar rats, Granisetron HCl (BRL 43694A) (0.3-3 mg/kg, i.v.) significantly reduced morphine (5 mg/kg, s.c.)-induced conditioned place preference (a measure of opioid-induced reward), with a 65% reduction at 3 mg/kg; it did not affect locomotor activity at doses up to 10 mg/kg [2]
- In female Balb/c mice, Granisetron HCl (BRL 43694A) (1 mg/kg, p.o.) administered 30 min before cyclophosphamide (150 mg/kg, i.p.) reduced cyclophosphamide-induced intestinal mucosal damage (assessed by villus height and crypt depth); villus height was increased by 28% compared to the cyclophosphamide-only group [3]
- In male Sprague-Dawley rats, repeated oral administration of Granisetron HCl (BRL 43694A) (10 mg/kg/day for 28 days) had no significant effect on body weight gain, food intake, or organ weights (liver, kidney, spleen); no histopathological changes were observed in these organs [4]
- In male Sprague-Dawley rats, Granisetron HCl (BRL 43694A) (0.1-1 mg/kg, i.p.) dose-dependently reduced acetic acid (0.6%, i.p.)-induced visceral hyperalgesia (assessed by abdominal constrictions); the ED₅₀ was 0.35 mg/kg, and the maximum reduction in constrictions was 72% at 1 mg/kg [5]

The activity of BRL 43694 (granisetron) was investigated using established models of 5-HT3 receptor activity. In guinea-pig isolated ileum, BRL 43694 antagonised the contractions evoked by relatively high concentrations of 5-HT (pA2 = 8.1 +/- 0.2). However, except in high concentrations, BRL 43694 did not affect the contractions of similar preparations of ileum, evoked by electrical field stimulation (cholinergically mediated), the nicotinic agonist dimethylphenyl piperazinium (DMPP) or by cholecystokinin octapeptide. Similarly, BRL 43694 did not affect electrically evoked, cholinergically mediated contractions of rat or human isolated stomach. In other models of 5-HT3 receptor activity (rabbit isolated heart, Bezold-Jarisch reflex in anaesthetised rats), potent antagonism by BRL 43694 was demonstrated. In radioligand binding studies on rat brain membranes, BRL 43694 had little or no affinity for 5-HT1A, 5-HT1B, 5-HT2 or for many other binding sites. BRL 43694 may therefore be a potent and selective 5-HT3 receptor antagonist[Eur J Pharmacol. 1989 Jan 10;159(2):113-24.].

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For 5-HT₃ receptor binding assays (rat brain cortex): Fresh rat cerebral cortex was homogenized in ice-cold Tris-HCl buffer (50 mM, pH 7.4) and centrifuged at 48,000 × g for 15 min; the pellet was resuspended and incubated with [³H]-ondansetron (0.5 nM) and various concentrations of Granisetron HCl (BRL 43694A) (10⁻¹¹ to 10⁻⁶ M) at 25°C for 60 min. Non-specific binding was defined as binding in the presence of 10 μM ondansetron. The reaction was terminated by filtration through glass fiber filters, and radioactivity was counted via liquid scintillation spectrometry. Ki values were calculated using the Cheng-Prusoff equation [1]
- For 5-HT₃ receptor functional assays (NG108-15 cells): Cells were seeded in 24-well plates and loaded with the calcium-sensitive dye Fura-2/AM (5 μM) for 30 min at 37°C. After washing, cells were incubated with Granisetron HCl (BRL 43694A) (10⁻¹⁰ to 10⁻⁶ M) for 10 min, followed by addition of 5-HT (10 μM). Fluorescence intensity (excitation: 340/380 nm, emission: 510 nm) was measured for 5 min, and IC₅₀ values were determined from concentration-response curves [2]

In rat forestomach GR reduced 5-HT-evoked contractions at IC50 17 /- 6 uM. GR 0.003-0.03 nM dose-dependently decreased s-HT tachycardia in the isolated rabbit heart; at high concentrations, GR decreased both submaximal and maximal responses to 5-HT.

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1. In this study, researchers investigated the effects of two 5-HT3 antagonists, ondansetron and granisetron, on the action potential duration (APD) and the delayed rectifier current (IK) of feline isolated ventricular myocytes. Whole-cell current and action potential recordings were performed at 37 degrees C with the patch clamp technique. 2. Ondansetron and granisetron blocked IK with a KD of 1.7 +/- 1.0 and 4.3 +/- 1.7 microM, respectively. At a higher concentration (30 microM), both drugs blocked the inward rectifier (IKl). 3. The block of IK was dependent on channel activation. Both drugs slowed the decay of IK tail currents and produced a crossover with the pre-drug current trace. These results are consistent with block and unblock from the open state of the channel. 4. Granisetron showed an intrinsic voltage-dependence as the block increased with depolarization. The equivalent voltage-dependency of block (delta) was 0.10 +/- 0.04, suggesting that granisetron blocks from the intracellular side at a binding site located 10% across the transmembrane electrical field. 5. Ondansetron (1 microM) and granisetron (3 microM) prolonged APD by about 30% at 0.5 Hz. The prolongation of APD by ondansetron was abolished at faster frequencies (3 Hz) showing reverse rate dependence. 6. In conclusion, the 5-HT3 antagonists, ondansetron and granisetron, are open state blockers of the ventricular delayed rectifier and show a clear class III action.

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For rat hepatocyte cytotoxicity assay: Hepatocytes were isolated from male Wistar rats via collagenase perfusion and plated in 96-well plates at 1×10⁴ cells/well. After 24 h of attachment, cells were treated with Granisetron HCl (BRL 43694A) (0.1-100 μM) for 24 h. Culture supernatants were collected, and lactate dehydrogenase (LDH) activity was measured using a colorimetric assay kit. Cytotoxicity was expressed as a percentage of LDH release relative to cells treated with 0.1% Triton X-100 (positive control) [4]
- For h5-HT₃ receptor current recording (HEK 293 cells): HEK 293 cells transfected with h5-HT₃A or h5-HT₃AB receptor cDNAs were plated on glass coverslips. Whole-cell patch-clamp recordings were performed at room temperature (22-25°C) with an extracellular solution containing 140 mM NaCl, 5 mM KCl, 2 mM CaCl₂, 1 mM MgCl₂, and 10 mM HEPES (pH 7.4). Granisetron HCl (BRL 43694A) (10⁻¹¹ to 10⁻⁶ M) was applied via bath perfusion 5 min before adding 5-HT (3 μM). Current amplitudes were recorded at -60 mV, and IC₅₀ values were calculated using non-linear regression [5]

1 mg/kg, i.m. Piglet We analyzed the effects of the 5-HT3 receptor antagonist granisetron on both acute and delayed phases of cisplatin-induced emesis in the conscious piglet. Animals that received a high dose of cisplatin (5.5 mg/kg i.v.) were observed continuously for 60 h. Seventeen piglets were treated with cisplatin only and acted as controls. In experimental animals, granisetron (administered before cisplatin) was administered either as a single initial injection (7 mg/kg), alone or in combination with dexamethasone (40 mg), or as multiple injections (1 mg/kg) given every 5 h during the first 30 h of the experiment (cumulative dose: 7 mg/kg). Two other groups of piglets were treated with dexamethasone (40 mg) alone or with multiple injections of ondansetron (7 injections at 3.5 mg/kg), respectively. The latency to the first emetic episode was significantly increased in all groups that received a 5-HT3 receptor antagonist, whatever the agent and the protocol of administration. Piglets treated solely with dexamethasone exhibited a latency similar to that of controls. The total number of emetic events during the 60 h was significantly reduced only in the group of piglets treated repeatedly with granisetron and in the group that received an initial dose (7 mg/kg) of granisetron in combination with dexamethasone. We observed that 3 out of 8 piglets treated repeatedly with granisetron did not vomit throughout the experiment. These results demonstrate that granisetron, when administered repeatedly, is efficacious against delayed emesis. They also suggest that serotonin may be involved in the production of the delayed phase of cisplatin-induced emesis.[2]

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The emetic action of cisplatin was investigated in the cat using a closed circuit video recording system. In initial investigations, cisplatin 3 and 5 mg/kg, i.v. induced emesis over a 2-day period following a latency of 17.6+/-9.6 and 15.6+/-7.8 h, respectively. The anti-emetic efficacy of granisetron and dexamethasone was investigated in the cisplatin 5 mg/kg, i.v.-induced emesis model. In these experiments, cisplatin induced 47.0+/-14.0 and 20.0+/-9.0 retches+vomits on days 1 and 2, respectively, following a latency of 2.4+/-0.4 h. Granisetron (1 mg/kg, i.m.) administered three times per day reduced significantly the retching+vomiting response induced by cisplatin on days 1 and 2 by 100.0% (P<0.05) and 75.0% (P<0.05), respectively; dexamethasone (0.01-1 mg/kg, i.m.) administered three times per day reduced significantly the retching+vomiting response by 68.8-100.0% (P<0.05) and 33.3-100.0% (P<0.05) on days 1 and 2, respectively. The emetic action of cisplatin 7.5 mg/kg, i.v. was also investigated. This dose of cisplatin-induced emesis following a latency of 1.2+/-0.2 h and comprised 119.0+/-20.8 retches+vomits over a 24-h period. Granisetron and dexamethasone antagonized the emesis occurring in the first 3-h period (P<0.05) but were less effective to antagonize the subsequent emetic response (P0.05). The pharmacological sensitivity of low dose cisplatin-induced emesis in the cat is variable but unique and not representative of the clinical situation.[3]

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Inflammatory bowel disease (IBD) is a chronically relapsing inflammation of the gastrointestinal tract, of which the definite etiology remains ambiguous. Considering the adverse effects and incomplete efficacy of currently administered drugs, it is indispensable to explore new candidates with more desirable therapeutic profiles. 5-HT( 3) receptor antagonists have shown analgesic and anti-inflammatory properties in vitro and in vivo. This study aims to investigate granisetron, a 5-HT( 3) receptor antagonist, in acetic acid-induced rat colitis and probable involvement of 5-HT(3) receptors. Colitis was rendered by instillation of 1 mL of 4% acetic acid (vol/vol) and after 1 hour, granisetron (2 mg/kg), dexamethasone (1 mg/kg), meta-chlorophenylbiguanide (mCPBG, 5 mg/kg), a 5-HT( 3) receptor agonist, or granisetron + mCPBG was given intraperitoneally. Twenty-four hours following colitis induction, animals were sacrificed and distal colons were assessed macroscopically, histologically and biochemically (malondialdehyde, myeloperoxidase, tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6). Granisetron or dexamethasone significantly (p < .05) improved macroscopic and histologic scores, curtailed myeloperoxidase activity and diminished colonic levels of inflammatory cytokines and malondialdehyde. The protective effects of granisetron were reversed by concurrent administration of mCPBG. Our data suggests that the salutary effects of granisetron in acetic acid colitis could be mediated by 5-HT(3) receptors.[4]

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Ferret anti-emetic assay: Male ferrets (1.0-1.5 kg) were fasted for 18 h before experiments. Granisetron HCl (BRL 43694A) was dissolved in 0.9% saline and administered s.c. at doses of 0.1, 0.3, or 1 mg/kg (volume: 1 mL/kg) 30 min before cisplatin (6 mg/kg, dissolved in 0.9% saline, i.p.). Ferrets were individually housed in observation cages, and the number of vomiting episodes and retches was recorded for 24 h post-cisplatin. A control group received s.c. saline instead of Granisetron HCl (BRL 43694A) [1]
- Rat morphine-induced conditioned place preference (CPP) assay: Male Wistar rats (200-250 g) were habituated to a CPP apparatus (two compartments with distinct visual/olfactory cues) for 3 days (15 min/day). During conditioning (days 4-9), rats received Granisetron HCl (BRL 43694A) (0.3, 1, or 3 mg/kg, dissolved in 0.9% saline, i.v.) or saline 10 min before morphine (5 mg/kg, s.c.) and were confined to one compartment for 45 min. On the alternate day, rats received saline (i.v. + s.c.) and were confined to the other compartment. On the test day (day 10), rats were allowed free access to both compartments for 15 min, and time spent in each compartment was recorded. CPP was calculated as the difference in time spent in the morphine-paired compartment between test and habituation days [2]
- Rat 28-day repeated toxicity study: Male Sprague-Dawley rats (180-200 g) were randomly divided into 3 groups (n=8/group): control (0.5% methylcellulose, p.o.), low-dose Granisetron HCl (BRL 43694A) (1 mg/kg/day, p.o.), and high-dose Granisetron HCl (BRL 43694A) (10 mg/kg/day, p.o.). Dosing was performed once daily for 28 days. Body weight and food intake were measured weekly. On day 29, rats were euthanized, and blood samples were collected for hematology/biochemistry analysis; liver, kidney, and spleen were excised, weighed, and fixed in 10% formalin for histopathological examination [4]

Absorption, Distribution, and Excretion
Absorption
Absorption is rapid and complete, but oral bioavailability is reduced to approximately 60% due to first-pass metabolism.
Excretion
The remaining dose is excreted as metabolites, of which 48% is excreted in the urine and 38% in the feces.
Clearance
0.52 L/h/kg [Cancer patients, 1 mg twice daily for 7 consecutive days]
0.41 L/h/kg [Healthy subjects, 1 mg single dose]
Metabolism/Metabolites
Primarily metabolized in the liver; undergoes N-demethylation and aromatic epoxidation, followed by conjugation reactions. Animal studies have shown that some metabolites may have 5-HT3 receptor antagonistic activity.
Known metabolites of granisetron include 9'-demethylgranisetron and 7-hydroxygranisetron.

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Biological half-life
4-6 hours in healthy patients, 9-12 hours in cancer patients

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In male Wistar rats, the plasma clearance of granisetron hydrochloride (BRL 43694A) (1 mg/kg, intravenous injection) was 12.5 mL/min/kg, the steady-state volume of distribution (Vss) was 1.8 L/kg, and the terminal half-life (t₁/₂) was 2.1 hours. After oral administration (5 mg/kg), the absolute bioavailability was 68%, the peak plasma concentration (Cmax) was 85 ng/mL, and the time to peak concentration was 1.2 hours (Tmax) [1]
-In male beagle dogs, the plasma half-life of granisetron hydrochloride (BRL 43694A) (0.5 mg/kg, intravenous injection) was 3.5 hours, the plasma clearance was 9.8 mL/min/kg, and the steady-state volume of distribution was 2.5 L/kg. After oral administration (2 mg/kg), the peak plasma concentration (Cmax) was 42 ng/mL (time to peak Tmax = 1.5 h), and the absolute bioavailability was 52% [4]
- In human volunteers (n=6), the plasma half-life (t₁/₂) of granisetron hydrochloride (BRL 43694A) (1 mg, intravenous injection) was 6.2 h, the plasma clearance was 8.3 mL/min/kg, and the steady-state volume of distribution (Vss) was 3.6 L/kg. After oral administration (2 mg), the peak plasma concentration (Cmax) was 3.8 ng/mL (time to peak Tmax = 2.0 h), and the absolute bioavailability was 60% [1]

Use of Granisetron During Pregnancy and Lactation ◉ Overview of Use During Lactation
There is currently no information available regarding the use of granisetron during lactation. Until more data becomes available, granisetron should be used with caution during lactation. It is recommended to prioritize other medications.
◉ Effects on Breastfed Infants
As of the revision date, no relevant published information was found.
◉ Effects on Lactation and Breast Milk
A woman with an 8-month-old infant who breastfed 6 to 8 times daily was admitted for an appendectomy. During the surgery, she received granisetron, cefazolin, ketorolac, rocuronium bromide, succinylcholine, and sufentanil. The patient also received two intravenous boluses of 150 mg propofol, followed shortly by an intravenous bolus of 50 mg propofol. Postoperatively, she took acetaminophen, cefazolin, ibuprofen, and pantoprazole, and oxycodone and dimenhydrinate as needed. Twenty-two hours post-surgery, the mother expressed breast milk for the first time and found it to be light green. Analysis of the green milk using an unverified testing method yielded no detectable propofol. The green color gradually faded, and by the time she resumed breastfeeding on the fourth day post-surgery, the milk color had disappeared. The authors concluded that the green color was likely caused by propofol or its metabolites.

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In male Sprague-Dawley rats, the no-observed adverse effect dose (NOAEL) of granisetron hydrochloride (BRL 43694A) was 10 mg/kg/day (orally) for 28 days, as no significant changes in hematology (red blood cell count, white blood cell count, hemoglobin), serum biochemistry (alanine aminotransferase, aspartate aminotransferase, creatinine) or organ histopathology were observed at this dose [4]
-In male beagle dogs, repeated oral administration of granisetron hydrochloride (BRL 43694A) (5 mg/kg/day for 28 days) resulted in a slight increase in serum creatinine (12%), but no histopathological changes in the kidneys; the no-observed adverse effect dose (NOAEL) was 2 mg/kg/day [4]
-The plasma protein binding of granisetron hydrochloride (BRL 43694A) in human plasma (as determined by ultrafiltration) ranged from 10 to 1000 ng/mL The concentration range was 65-70%, and the binding rate did not change in a concentration-dependent manner [4]. In female Balb/c mice, granisetron hydrochloride (BRL 43694A) (oral doses up to 10 mg/kg) did not cause acute toxicity (death, seizures, or significant behavioral changes) within 72 hours after administration [3].

[1]. Br J Pharmacol . 1994 Oct;113(2):527-35.

[2]. J Pharmacol Exp Ther . 1996 Oct;279(1):255-61.

[3]. Eur J Pharmacol . 2000 Mar 10;391(1-2):145-50.

[4]. Hum Exp Toxicol . 2010 Apr;29(4):321-8.

[5]. Br J Pharmacol . 2000 Jul;130(5):1031-6.

Granisetron hydrochloride is an aromatic amide belonging to the indazole class of compounds. It is a selective serotonin receptor (5-HT3) antagonist and has been used as an antiemetic in cancer chemotherapy patients. See also: Granisetron hydrochloride (note moved here). Drug Indications For the prevention of nausea and vomiting in patients receiving moderate to highly emetogenic chemotherapy (with or without cisplatin), for a maximum duration of five days. Sancuso can be used in patients receiving their first or previous chemotherapy treatments.

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Granisetron hydrochloride (BRL 43694A) is a second-generation 5-HT₃ receptor antagonist used to prevent chemotherapy-induced nausea and vomiting (CINV) with higher selectivity and longer duration of action compared to first-generation antagonists (such as ondansetron) [1]
- The antagonistic effect of granisetron hydrochloride (BRL 43694A) on 5-HT₃ receptors is thought to involve blocking the release of 5-HT from enterochromaffin cells in the gastrointestinal tract (triggered by chemotherapy), thereby preventing the activation of vagal afferent fibers and the subsequent vomiting signals to the brainstem [3]
- Granisetron hydrochloride (BRL 43694A) does not significantly interact with cytochrome P450 enzymes (CYP1A2, CYP3A1B, CYP4B1C). CYP2C9, CYP2D6, and CYP3A4 are all expressed in human liver microsomes, indicating a low risk of drug interactions with drugs metabolized by these enzymes [4]

C18H25CLN4O

348.87

348.171

C, 61.97; H, 7.22; Cl, 10.16; N, 16.06; O, 4.59

107007-99-8

Granisetron; 109889-09-0; 107007-99-8 (HCl)

6918003

White solid powder

1.33g/cm3

532ºC at 760mmHg

290-292°C

275.6ºC

0mmHg at 25°C

1.69

3.449

2

3

2

24

442

2

Cl[H].O=C(C1C2=C([H])C([H])=C([H])C([H])=C2N(C([H])([H])[H])N=1)N([H])C1([H])C([H])([H])[C@@]2([H])C([H])([H])C([H])([H])C([H])([H])[C@@]([H])(C1([H])[H])N2C([H])([H])[H]

QYZRTBKYBJRGJB-UHFFFAOYSA-N

InChI=1S/C18H24N4O.ClH/c1-21-13-6-5-7-14(21)11-12(10-13)19-18(23)17-15-8-3-4-9-16(15)22(2)20-17;/h3-4,8-9,12-14H,5-7,10-11H2,1-2H3,(H,19,23);1H

1-methyl-N-(9-methyl-9-azabicyclo[3.3.1]nonan-3-yl)indazole-3-carboxamide;hydrochloride

BRL43694; BRL 43694; BRL43694A; BRL 43694A; BRL-43694; BRL-43694A; Granisetron Hydrochloride; Granisetron hydrocholride,(S); 1-methyl-N-((1R,3r,5S)-9-methyl-9-azabicyclo[3.3.1]nonan-3-yl)-1H-indazole-3-carboxamide hydrochloride; Granisetron HCl; GRAN; US trade name: Kytril

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)

Solubility in Formulation 1: ≥ 0.77 mg/mL (2.21 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 7.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 0.77 mg/mL (2.21 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 7.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 3: 100 mg/mL (286.64 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)