CX546

Biological Activity

CX546 is a selective positive AMPA glutamate receptor modulator. CX546 caused an approximately 2-fold increase in the affinity for radiolabeled agonists, whereas CX516 was ineffective. CX546 enhances cognitive function in rats. Administration of CX546 improved the disrupted LI in mGluR5 knockout mice and facilitated LI in control C57BL/6J mice, given extended number of conditioning trails.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

Chemical Information

References

The ampakine CX546 restores the prepulse inhibition and latent inhibition deficits in mGluR5-deficient mice
Tatiana Lipina, et al. Neuropsychopharmacology. 2007 Apr;32(4):745-56. PMID: 16936708.

Benzamide-type AMPA receptor modulators form two subfamilies with distinct modes of action
Amy C Arai, et al. J Pharmacol Exp Ther. 2002 Dec;303(3):1075-85. PMID: 12438530.

Positive modulation of AMPA receptors increases neurotrophin expression by hippocampal and cortical neurons
J C Lauterborn, et al. J Neurosci. 2000 Jan 1;20(1):8-21. PMID: 10627576.