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Farampator (also known as CX-691 or Org24448) is a positive and allosteric modulator of the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid) receptor. CX691 attenuated a scopolamine-induced impairment of cued fear conditioning following acute administration (0.1 mg/kg p.o.) and a temporally induced deficit in novel object recognition following both acute (0.1 and 1.0 mg/kg p.o.) and sub-chronic (bi-daily for 7 days) administration (0.01, 0.03, 0.1 mg/kg p.o.). It also improved attentional set-shifting following sub-chronic administration (0.3 mg/kg p.o.). Thus, Farampator may have utility for the treatment of cognitive impairment such as such as Alzheimer's disease and schizophrenia.
Physicochemical Properties
| Molecular Formula | C12H13N3O2 | |
| Molecular Weight | 231.26 | |
| Exact Mass | 231.1 | |
| CAS # | 211735-76-1 | |
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| PubChem CID | 4118151 | |
| Appearance | White to off-white solid powder | |
| Density | 1.3±0.1 g/cm3 | |
| Boiling Point | 398.3±34.0 °C at 760 mmHg | |
| Flash Point | 194.7±25.7 °C | |
| Vapour Pressure | 0.0±0.9 mmHg at 25°C | |
| Index of Refraction | 1.621 | |
| LogP | 0.91 | |
| Hydrogen Bond Donor Count | 0 | |
| Hydrogen Bond Acceptor Count | 4 | |
| Rotatable Bond Count | 1 | |
| Heavy Atom Count | 17 | |
| Complexity | 292 | |
| Defined Atom Stereocenter Count | 0 | |
| InChi Key | XFVRBYKKGGDPAJ-UHFFFAOYSA-N | |
| InChi Code | InChI=1S/C12H13N3O2/c16-12(15-6-2-1-3-7-15)9-4-5-10-11(8-9)14-17-13-10/h4-5,8H,1-3,6-7H2 | |
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| 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 |
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| 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
| Targets |
The target of Farampator (CX-691, Org24448) is the α-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) receptor, acting as a positive allosteric modulator of this receptor. [1] - Farampator (CX-691, Org24448) targets the AMPA-type glutamate receptors as a positive allosteric modulator. [2] |
| ln Vitro |
In vitro activity: Farampator (also known as CX-691 or Org24448) is a positive and allosteric modulator of the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid) receptor. Kinase Assay: The objective of the study was to investigate the effect of an AMPA positive modulator, CX691, 1) brain-derived neurotrophic factor (BDNF) messenger RNA (mRNA) expression in the rat hippocampus following acute and sub-chronic administration; 2) on neurochemistry in the dorsal hippocampus and medial prefrontal cortex following acute administration. Cell Assay: |
| ln Vivo |
Farampator may be used to treat conditions like schizophrenia and Alzheimer's disease that are characterized by cognitive impairments. CX691 reduces the effects of scopolamine on cued fear conditioning after acute administration (0.1 mg/kg po) and a temporally induced deficit in novel object recognition after sub-chronic (bi-daily for 7 days) and acute (0.1 and 1.0 mg/kg po) administration (0.01, 0.03, 0.1 mg/kg po). Additionally, after sub-chronic dosing (0.3 mg/kg po), it enhances attentional set-shifting[1]. Unquestionably, farampator (500 mg) enhances short-term memory, but it seems to degrade episodic memory. Moreover, it tends to reduce the CTMT's number of switching faults. Among the drug-induced side effects (SEs) were nausea, somnolence, and headache. Compared to participants without SEs, subjects with SEs had noticeably greater plasma levels of farampator[2]. In rats, acute oral administration of Farampator (CX-691, Org24448) at a dose of 0.1 mg/kg attenuated a scopolamine-induced impairment of cued fear conditioning. Both acute oral administration (0.1 and 1.0 mg/kg) and sub-chronic oral administration (bi-daily for 7 days at doses of 0.01, 0.03, 0.1 mg/kg) alleviated a temporally induced deficit in novel object recognition. Sub-chronic oral administration at 0.3 mg/kg improved attentional set-shifting. Acute oral doses of 0.1, 0.3 and 1.0 mg/kg increased extracellular levels of acetylcholine in the dorsal hippocampus and medial prefrontal cortex, and elevated dopamine levels in the medial prefrontal cortex. Sub-chronic oral administration of 0.1 mg/kg elevated brain-derived neurotrophic factor (BDNF) messenger RNA (mRNA) expression in both the whole hippocampus and the CA1 sub-region of the hippocampus (P < 0.05) [1] - In a double-blind, placebo-controlled, randomized, cross-over study involving 16 healthy elderly volunteers (eight male, eight female; mean age 66.1, SD 4.5 years), acute administration of Farampator (CX-691, Org24448) at a dose of 500 mg (oral intake) unequivocally improved short-term memory (assessed by N-back, symbol recall tasks), but appeared to impair episodic memory (assessed by wordlist learning and picture memory tasks). It also tended to decrease the number of switching errors in the continuous trail making test (CTMT). Information processing was assessed with a tangled lines task, the symbol digit substitution test (SDST) and the CTMT, with no significant overall impairments observed in these aspects except for the trend in CTMT [2] |
| Animal Protocol |
0.1-1.0 mg/kg; p.o. Three rodent models of learning and memory For the cued fear conditioning experiment: Male rats were used. Farampator (CX-691, Org24448) was administered orally at a dose of 0.1 mg/kg. Scopolamine was given to induce impairment of cued fear conditioning. The rats were then subjected to the cued fear conditioning paradigm, which included a conditioning phase (pairing a cue with an aversive stimulus) and a testing phase (presenting the cue alone to measure the conditioned response). The conditioned fear responses of the rats were recorded and analyzed to evaluate the effect of the drug on scopolamine-induced impairment. For the novel object recognition experiment: Rats received acute oral doses of 0.1 and 1.0 mg/kg Farampator (CX-691, Org24448), or sub-chronic oral doses (bi-daily for 7 days) of 0.01, 0.03, 0.1 mg/kg. A temporal deficit in novel object recognition was induced (the specific induction method was not detailed in the abstract). The rats were first exposed to two identical objects during a familiarization phase, and then presented with a familiar object and a novel object during the test phase. The time spent exploring the novel object relative to the familiar object was measured to assess recognition memory. For the attentional set-shifting experiment: Rats were given sub-chronic oral administration of 0.3 mg/kg Farampator (CX-691, Org24448). The attentional set-shifting task was conducted, which involved a series of discrimination problems (simple discrimination, compound discrimination, intra-dimensional shift, extra-dimensional shift) to evaluate the rats' ability to shift attention and form attentional sets. The number of errors and the time to complete each stage of the task were recorded. For the neurochemical measurement experiment: Rats were acutely administered Farampator (CX-691, Org24448) orally at doses of 0.1, 0.3 and 1.0 mg/kg. Microdialysis probes were implanted into the dorsal hippocampus and medial prefrontal cortex to collect extracellular fluid samples at different time points after drug administration. The levels of acetylcholine and dopamine in the samples were quantified using high-performance liquid chromatography (HPLC) or other appropriate analytical techniques. For the BDNF mRNA expression experiment: Rats received sub-chronic oral administration of 0.1 mg/kg Farampator (CX-691, Org24448) (bi-daily for 7 days). After the treatment period, the rats were sacrificed, and the hippocampal tissues (whole hippocampus and CA1 sub-region) were collected. In situ hybridization was performed to detect the expression of BDNF mRNA, and the hybridization signals were quantified to determine the changes in BDNF mRNA levels [1] - No animal experiments were conducted in this study; instead, human clinical trials were carried out on healthy elderly volunteers. Thus, no animal protocol related to Farampator (CX-691, Org24448) was described [2] |
| ADME/Pharmacokinetics |
In healthy elderly volunteers, the maximum plasma concentration (Tmax) of Farampator (CX-691, Org24448) occurred around 1 hour after oral intake of 500 mg. Subjects who experienced side effects had significantly higher plasma levels of the drug than those who did not, [2] |
| Toxicity/Toxicokinetics |
In healthy elderly volunteers, acute oral administration of Farampator (CX-691, Org24448) at 500 mg caused side effects including headache, somnolence and nausea. Subjects with side effects had significantly higher plasma levels of the drug compared to those without side effects. No information about liver and kidney toxicity, drug-drug interactions, or plasma protein binding was provided [2] |
| References |
[1]. Evaluation of the pro-cognitive effects of the AMPA receptor positive modulator, 5-(1-piperidinylcarbonyl)-2,1,3-benzoxadiazole (CX691), in the rat. Psychopharmacology (Berl). 2009 Jan;202(1-3):343-54. [2]. Acute effects of the ampakine farampator on memory and information processing in healthy elderly volunteers. Neuropsychopharmacology. 2007 Jun;32(6):1272-83. |
| Additional Infomation |
Farampator is under investigation in clinical trial NCT00113022 (Org 24448 to Treat Major Depression). Positive allosteric modulators of the glutamatergic AMPA receptor, such as Farampator (CX-691, Org24448), do not stimulate AMPA receptors directly but delay deactivation of the receptor and/or slow its desensitisation, resulting in increased synaptic responses and enhanced long-term potentiation. These compounds may have utility for the treatment of cognitive impairment, such as in Alzheimer's disease and schizophrenia [1] - Ampakines like Farampator (CX-691, Org24448) act as positive allosteric modulators of AMPA-type glutamate receptors and facilitate hippocampal long-term potentiation (LTP), a mechanism associated with memory storage and consolidation. The positive results of the drug on short-term memory and the favorable trends in the CTMT are interesting in view of the development of ampakines in the treatment of Alzheimer's disease and schizophrenia [2] |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.81 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 (10.81 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 (10.81 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 | 4.3241 mL | 21.6207 mL | 43.2414 mL | |
| 5 mM | 0.8648 mL | 4.3241 mL | 8.6483 mL | |
| 10 mM | 0.4324 mL | 2.1621 mL | 4.3241 mL |