Carisbamate (RWJ-333369) is an orally bioavailable neuromodulator. Carisbamate prevents the development and generation of epileptiform discharges and has neuro-protective (neuro-protection) effects after epileptiform injury in vitro. Carisbamate has promising antiepileptic activity in genetic models of generalized convulsive and nonconvulsive epilepsy.

Physicochemical Properties

Molecular Formula	C9H10CLNO3
Molecular Weight	215.63400
Exact Mass	215.035
CAS #	194085-75-1
Related CAS #	Carisbamate-d4;1292841-50-9;(R)-Carisbamate-d4;1287128-99-7;(Rac)-Carisbamate-d4;1329808-36-7
PubChem CID	6918474
Appearance	White to off-white solid powder
LogP	2.169
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	4
Heavy Atom Count	14
Complexity	201
Defined Atom Stereocenter Count	1
SMILES	C1=CC=C(C(=C1)[C@@H](COC(=O)N)O)Cl
InChi Key	OLBWFRRUHYQABZ-MRVPVSSYSA-N
InChi Code	InChI=1S/C9H10ClNO3/c10-7-4-2-1-3-6(7)8(12)5-14-9(11)13/h1-4,8,12H,5H2,(H2,11,13)/t8-/m1/s1
Chemical Name	[(2S)-2-(2-chlorophenyl)-2-hydroxyethyl] carbamate
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	In the SRED model of hippocampus cells, carisbamate (200 µM; 12 hours) exhibits anti-epileptic properties [1]. Long-lasting effects on hippocampal neurons are demonstrated by carisbamate (200 µM; 24 hours), which are not correlated with antiepileptic effects in vitro [1]. In the few neurons that still occasionally experience epileptiform events, carisbamate not only inhibits the development and expression of SRED in the majority of neurons, but it also shortens the duration and frequency of seizures [1]. Hippocampal cells with injury resembling status epilepticus can benefit from neuroprotective actions of carisbamate (200 µM) [1].
ln Vivo	Carisbamate (10, 30, 60 mg/kg; intraperitoneal injection; single dosage) dose-dependently lowers the expression of spike-wave discharges (SWD) in a rat model of absence seizures [2]. Carisbamate (20, 30 mg/kg; i.p.; single dosage) did not elicit galloping or tonic seizures in any of the rats examined [2].
Cell Assay	Cell Viability Assay[1] Cell Types: Hippocampal cells (from postnatal day 2 Sprague-Dawley rats; Spontaneous Recurrent Epileptiform Discharges (SRED) model) Tested Concentrations: 200 µM Incubation Duration: 12 hrs (hours) Experimental Results: Response to SRED The acute inhibition rate is greater than 95% of neurons showing anti-epileptic effects in vitro. Cell viability assay[1] Cell Types: Hippocampal cells (SREDs model) Tested Concentrations: 200 µM Incubation Duration: 24 hrs (hours) Experimental Results: Display cells evaluated the day after treatment still had no in vitro epileptic activity and no SREDs were formed.
Animal Protocol	Animal/Disease Models: Male genetic absence epilepsy rat (absence seizure model) [2]. Doses: 10, 30, 60 mg/kg Route of Administration: intraperitoneal (ip) injection; single. Experimental Results: SWD was completely inhibited after 120 min at 60 mg/kg, and SWD duration returned to control levels after 100 min at 30 mg/kg. Animal/Disease Models: Male Wistar hearing-sensitive rat (convulsive seizure model) [2]. Doses: 10, 20, 30 mg/kg Route of Administration: intraperitoneal (ip) injection; single. Experimental Results: At doses of 20 and 30 mg/kg, none of the rats tested developed galloping or tonic seizures. At a dose of 10 mg/kg, 6 of the 8 rats studied still developed tonic seizure latency, which increased by 327%.
References	[1]. Carisbamate prevents the development and expression of spontaneous recurrent epileptiform discharges and is neuroprotective in cultured hippocampal neurons. Epilepsia. 2008 Oct;49(10):1795-802. [2]. Effects of carisbamate (RWJ-333369) in two models of genetically determined generalized epilepsy, the GAERS and the audiogenic Wistar AS. Epilepsia. 2008 Mar;49(3):393-9. [3]. Carisbamate (RWJ-333369). Neurotherapeutics. 2007 Jan;4(1):106-9.
Additional Infomation	Carisbamate is an organochlorine compound. Carisbamate has been investigated in Alcohol Abuse, Substance Abuse, and Alcohol Dependence. Drug Indication Infantile spasms (West Syndrome), Lennox-Gastaut Syndrome, Localization-related (focal)(partial) symptomatic epilepsy and epileptic syndromes with simple partial seizures, Neonatal seizures, Other paediatric epilepsy syndromes such as Dravet Syndrome, myoclonic astatic syndrome, epilepsy with continuous sharp-waves in sleep, idiopathic partial epilepsy, absence epilepsy

Solubility Data

Solubility (In Vitro)

DMSO : ≥ 100 mg/mL (~463.76 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (11.59 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (11.59 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (11.59 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	4.6376 mL	23.1879 mL	46.3757 mL
	5 mM	0.9275 mL	4.6376 mL	9.2751 mL
	10 mM	0.4638 mL	2.3188 mL	4.6376 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.