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]

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].

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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]

0.1-1.0 mg/kg; p.o.
Three rodent models of learning and memory

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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]

In healthy elderly volunteers, peak plasma drug concentration (Tmax) was reached approximately 1 hour after oral administration of 500 mg Farampator (CX-691, Org24448). Plasma drug concentrations were significantly higher in subjects experiencing side effects than in those who did not. [2]

In healthy elderly volunteers, acute oral administration of 500 mg fraampasto (CX-691, Org24448) caused side effects such as headache, drowsiness, and nausea. Plasma drug concentrations in subjects experiencing side effects were significantly higher than in subjects who did not experience side effects. No information was provided regarding hepatotoxicity, nephrotoxicity, drug interactions, or plasma protein binding rates. [2]

[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.

Farampator is undergoing clinical trial NCT00113022 (Org 24448 for the treatment of major depressive disorder).

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Positive allosteric modulators of glutamatergic AMPA receptors, such as Farampator (CX-691, Org24448), do not directly stimulate AMPA receptors, but rather delay receptor inactivation and/or slow their desensitization, thereby enhancing synaptic responses and promoting long-term potentiation (LTP). These compounds may have potential applications in the treatment of cognitive disorders such as Alzheimer's disease and schizophrenia [1]
- Positive allosteric modulators of AMPA receptors, such as Farampator (CX-691, Org24448), can promote hippocampal long-term potentiation (LTP), a mechanism associated with memory storage and consolidation. The positive effects of this drug on short-term memory and the good trend shown in the CTMT test are noteworthy for the application prospects of ampacaine-like drugs in the treatment of Alzheimer's disease and schizophrenia [2]

C12H13N3O2

231.26

231.1

211735-76-1

4118151

White to off-white solid powder

1.3±0.1 g/cm3

398.3±34.0 °C at 760 mmHg

194.7±25.7 °C

0.0±0.9 mmHg at 25°C

1.621

0.91

0

4

1

17

292

0

XFVRBYKKGGDPAJ-UHFFFAOYSA-N

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

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 (10.81 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.

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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.

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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.

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