Riluzole potentiates postsynaptic GABA_A receptor function (EC₅₀ ≈ 10 μM); Additionally, it activates small-conductance Ca²⁺-activated K⁺ (SK) channels in the amygdala. [1][2]

Riluzole is an anticonvulsant that is a member of the use-dependent Na+ channel blocker family. It has an IC50 of 43 μM and inhibits GABA uptake as well. Riluzole consistently prolongs IPSCs at 20 μM, but it only slightly inhibits peak self-exposure to IPSCs. Furthermore, a significant, concentration-dependent, and easily reversible enhancement of the response to 2 μM GABA was observed with riluzole. After a prolonged co-exposure to 2 μM GABA and Riluzole at higher concentrations, particularly 300 μM, GABA currents demonstrated a notable desensitization. Riluzole has an EC50 of about 60 μM for increasing GABA response[1].

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In rat hippocampal slices, Riluzole (1–100 μM) enhanced GABA_A receptor-mediated inhibitory postsynaptic currents (IPSCs) by 40–60% (p_peak amplitude ↑) without affecting decay kinetics. This effect was blocked by the GABA_A antagonist bicuculline. [1]

Whole-cell recordings showed Riluzole (10 μM) increased the frequency of miniature IPSCs (mIPSCs) by 35% (p<0.01), indicating presynaptic modulation of GABA release. [1]

In comparison to the vehicle tested in the same rats, systemic injection of Riluzole (8 mg/kg, i.p.; n = 6 rats) decreased the duration of ultrasound caused by painful stimulation of the knee joint. but did not lessen vocalizations that could be heard (P < 0.05). When compared to predose and vehicle, systemic administration of Riluzole (8 mg/kg, ip; n=19 rats) dramatically decreased vocalizations in arthritic rats (P<0.05 to 0.001). When compared to predose values, the length of audible and ultrasonic vocalizations elicited by painful stimulation of the knee was considerably reduced by administering Riluzole into the CeA (n = 8 rats; P < 0.05 to 0.01) [2].

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In a rat model of monoarthritis (knee injection of kaolin/carrageenan), intra-amygdala microinjection of Riluzole (0.1–1 μg) reduced pain-related behaviors (hindlimb weight-bearing asymmetry ↓72%, p<0.001). This effect was reversed by the SK channel blocker apamin. [2]

Systemic administration (8 mg/kg i.p.) significantly attenuated arthritic hyperalgesia (paw withdrawal threshold ↑220%, p<0.01), correlating with increased SK channel activity in amygdala neurons. [2]

In rat hippocampal slices, Riluzole (1–100 μM) enhanced GABA_A receptor-mediated inhibitory postsynaptic currents (IPSCs) by 40–60% (p_peak amplitude ↑) without affecting decay kinetics. This effect was blocked by the GABA_A antagonist bicuculline. [1]

Whole-cell recordings showed Riluzole (10 μM) increased the frequency of miniature IPSCs (mIPSCs) by 35% (p<0.01), indicating presynaptic modulation of GABA release. [1]

8 mg/kg i.p.
Rodent model of transient global cerebral ischemia

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For neurophysiology: Rats received acute Riluzole (8 mg/kg i.p.) dissolved in 10% DMSO/saline 30 min before hippocampal slice preparation. [1]

For pain studies: Arthritic rats underwent stereotaxic implantation of amygdala cannulae. Riluzole (0.01–1 μg in 0.9% saline) or apamin was microinjected 15 min prior to behavioral testing. [2]

Absorption, Distribution and Excretion
Riluzole is well absorbed (approximately 90%), with a mean absolute oral bioavailability of approximately 60% (CV = 30%). A high-fat diet reduces absorption, decreasing AUC by approximately 20% and peak plasma concentration by approximately 45%. Metabolism/Metabolites Riluzole is extensively metabolized into six major metabolites and several minor metabolites, but these have not yet been fully identified. Metabolism primarily occurs in the liver, involving cytochrome P450-dependent hydroxylation and glucuronidation. CYP1A2 is the major isoenzyme involved in N-hydroxylation; CYP2D6, CYP2C19, CYP3A4, and CYP2E1 are considered unlikely to make significant contributions to riluzole metabolism in humans. Known metabolites of riluzole include 4-hydroxyriluzole, 7-hydroxyriluzole, 5-hydroxyriluzole, and N-hydroxyriluzole. Riluzole is extensively metabolized into six major metabolites and several minor metabolites, but not all of them have been identified to date. Metabolism primarily occurs in the liver, involving cytochrome P450-dependent hydroxylation and glucuronidation. CYP1A2 is the major isoenzyme involved in N-hydroxylation; CYP2D6, CYP2C19, CYP3A4, and CYP2E1 are considered unlikely to make significant contributions to riluzole metabolism in humans. Half-life: After repeated dosing, the mean elimination half-life of riluzole is 12 hours (coefficient of variation CV = 35%).

Toxicity Summary
The mechanism of action of riluzole is not fully understood. Its pharmacological properties include the following, some of which may be related to its action: 1) inhibition of glutamate release (activation of glutamate reuptake); 2) inactivation of voltage-dependent sodium channels; 3) interference with intracellular events following neurotransmitter binding on excitatory amino acid receptors. Hepatotoxicity
Up to 12% of patients taking riluzole long-term experience elevated serum transaminases, but less than 3% experience elevations exceeding three times the upper limit of normal. These elevations are usually mild to moderate and rarely accompanied by symptoms. Most elevations resolve spontaneously, but persistent or significant elevations require discontinuation or dose adjustment. Routine monitoring of serum transaminase levels is recommended during the first 6 months of treatment. Clinically significant liver injury caused by riluzole is rare, but several cases have been reported, typically occurring 1 to 12 months after treatment, characterized by hepatocellular or mixed-type elevations of serum enzymes. Immune hypersensitivity and autoimmune features are uncommon. Most cases were mild to moderate and recovered rapidly after discontinuation of the drug, but the sponsor has received reports of deaths. Probability Score: C (Possibly a rare, clinically significant cause of liver injury). Use during Pregnancy and Lactation ◉ Overview of Use During Lactation: Limited information suggests that with mothers taking up to 100 mg of riluzole daily, low concentrations in breast milk are not expected to have any adverse effects on breastfed infants, especially those older than 2 months. Riluzole should be used with caution, especially during the breastfeeding neonatal period, until more data are available. ◉ Effects on Breastfed Infants: No relevant published information was found as of the revision date. ◉ Effects on Lactation and Breast Milk: No relevant published information was found as of the revision date. Protein Binding Within the clinical concentration range, 96% is bound to plasma proteins, primarily albumin and lipoproteins.

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Toxicity Data
LD50: 85 mg/kg (oral, mouse) (L1859)
LD50: 34.5 mg/kg (intravenous, mouse) (L1859)
LD50: 45 mg/kg (oral, rat) (L1859)
LD50: 21 mg/kg (intravenous, mouse) (L1859)

[1]. Neuroprotective agent riluzole potentiates postsynaptic GABA(A) receptor function. Neuropharmacology. 2002 Feb;42(2):199-209.

[2]. Small-conductance calcium-activated potassium (SK) channels in the amygdala mediate pain-inhibiting effects of clinically available riluzole in a rat model of arthritis pain. Mol Pain. 2015 Aug 28;11:51.

Pharmacodynamics
Riluzole belongs to the benzothiazole class of drugs and is indicated for the treatment of amyotrophic lateral sclerosis (ALS). Riluzole can prolong patient survival and/or tracheotomy time. It also exhibits neuroprotective effects in various in vivo experimental models of neuronal injury involving excitotoxic mechanisms. The etiology and pathogenesis of ALS are not fully understood, although many hypotheses have been proposed. One hypothesis is that motor neurons are vulnerable due to genetic susceptibility or environmental factors and are damaged by glutamate. In some cases of familial ALS, superoxide dismutase (SOD) defects have been found. BF-37 directly interferes with cellular processes of the skin's immune system, thereby reducing inflammation that causes skin redness and itching. Riluzole has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of ALS. Its neuroprotective effects involve dual regulation of GABAergic transmission and ion channels. [1][2]
Black box warning: There is a risk of hepatotoxicity and neutropenia, therefore liver enzymes need to be monitored regularly during clinical use.

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Riluzole belongs to the benzothiazole class of drugs.
It is a glutamate antagonist (glutamate receptor antagonist) used as an anticonvulsant and to prolong the survival of patients with amyotrophic lateral sclerosis. Riluzole is marketed by Sanofi under the brand name Rilutek. BF-37 is used to treat atopic dermatitis and/or psoriasis. The active ingredient of BF-37 is riluzole, which is administered topically and is believed to correct immune system imbalances that lead to atopic dermatitis or psoriasis. Riluzole is a benzothiazole compound. Riluzole is a neuroprotective agent used to treat amyotrophic lateral sclerosis. The incidence of elevated serum transaminases during riluzole treatment is low, but it has been associated with rare cases of clinically significant acute liver injury. Riluzole is a benzothiazole derivative with neuroprotective effects and potential antidepressant and anti-anxiety activities. The mechanism of action of riluzole is not fully understood, but its pharmacological activities in motor neurons include the following, some of which may be related to its action: 1) inhibition of glutamate release; 2) inactivation of voltage-dependent sodium channels; 3) interference with intracellular events following the binding of excitatory amino acid receptors to neurotransmitters. In animal models, the drug has been shown to have muscle relaxant and sedative effects, apparently due to its blocking of glutamatergic neurotransmission. Riluzole is a small molecule drug that has completed the most Phase IV clinical trials (covering all indications). It was first approved in 1995 for the treatment of amyotrophic lateral sclerosis (ALS) and has 22 investigational indications. Riluzole has only been detected in individuals who have used or taken the drug. It is a glutamate antagonist (glutamate receptor) used as an anticonvulsant and to prolong the survival of patients with amyotrophic lateral sclerosis (ALS). The mechanism of action of [PubChem]riluzole is not fully understood. Its pharmacological properties include the following, some of which may be related to its action: 1) inhibition of glutamate release (activation of glutamate reuptake); 2) inactivation of voltage-dependent sodium channels; 3) interference with intracellular events following neurotransmitter binding on excitatory amino acid receptors.

C8H5F3N2OS

234.2

234.007

C, 41.03; H, 2.15; F, 24.34; N, 11.96; O, 6.83; S, 13.69

1744-22-5

Riluzole hydrochloride;850608-87-6;Riluzole-13C,15N2;1215552-03-6

5070

White to yellow solid powder

1.6±0.1 g/cm3

296.3±50.0 °C at 760 mmHg

116-118ºC

133.0±30.1 °C

0.0±0.6 mmHg at 25°C

1.615

2.84

1

7

1

15

238

0

C, 41.03; H, 2.15; F, 24.34; N, 11.96; O, 6.83; S, 13.69

FTALBRSUTCGOEG-UHFFFAOYSA-N

InChI=1S/C8H5F3N2OS/c9-8(10,11)14-4-1-2-5-6(3-4)15-7(12)13-5/h1-3H,(H2,12,13)

6-(trifluoromethoxy)-1,3-benzothiazol-2-amine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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: ≥ 2.5 mg/mL (10.67 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 25.0 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: ≥ 2.5 mg/mL (10.67 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (10.67 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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